fertilisation
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
where an
egg
An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...
is combined with
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) from their
ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
and letting sperm fertilise them in a culture medium in a laboratory. After the fertilised egg (
zygote
A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism.
In multicellula ...
) undergoes
embryo culture Embryo culture is a component of ''in vitro'' fertilisation where in resultant embryos are allowed to grow for some time in an artificial medium.
Duration
The duration of embryo culture can be varied, conferring different stages of embryogenesis ...
catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
into the
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
, with the intention of establishing a successful
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
.
IVF is a type of
assisted reproductive technology
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
used for
infertility
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
treatment,
gestational surrogacy
Surrogacy is an arrangement, often supported by a legal agreement, whereby a woman agrees to delivery/labour for another person or people, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnan ...
, and, in combination with
pre-implantation genetic testing
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
, avoiding transmission of genetic conditions. A fertilised egg from a donor may
implant
Implant can refer to:
Medicine
*Implant (medicine), or specifically:
** Brain implant
** Breast implant
**Buttock implant
**Cochlear implant
**Contraceptive implant
**Dental implant
** Fetal tissue implant
**Implantable cardioverter-defibrillator ...
into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. Some countries have banned or otherwise regulate the availability of IVF treatment, giving rise to
fertility tourism
Fertility tourism (also referred to as reproductive tourism or cross border reproductive care) is the practice of traveling to another country or jurisdiction for fertility treatment, and may be regarded as a form of medical tourism. One can usuall ...
. Restrictions on the availability of IVF include costs and age, in order for a woman to carry a healthy pregnancy to term. Children born through IVF are commonly called test tube babies.
In July 1978,
Louise Brown
Louise Joy Brown (born 25 July 1978) is an English woman who was the first human to have been born after conception by ''in vitro'' fertilisation experiment (IVF). Her birth, following a procedure pioneered in Britain, has been lauded among "t ...
was the first child successfully born after her mother received IVF treatment. Brown was born as a result of natural-cycle IVF, where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (now Dr Kershaw's Hospice) in
Royton
Royton is a town in the Metropolitan Borough of Oldham, Greater Manchester, England, with a population of 21,284 in 2011. Close to the source of the River Irk, near undulating land at the foothills of the South Pennines, it is northwest of Old ...
, Oldham, England.
Robert G. Edwards
Sir Robert Geoffrey Edwards (27 September 1925 – 10 April 2013) was a British physiologist and pioneer in reproductive medicine, and in-vitro fertilisation (IVF) in particular. Along with obstetrician and gynaecologist Patrick Steptoe ...
was awarded the
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
in 2010. The physiologist co-developed the treatment together with
Patrick Steptoe
Patrick Christopher Steptoe CBE FRS (9 June 1913 – 21 March 1988) was an English obstetrician and gynaecologist and a pioneer of fertility treatment. Steptoe was responsible with biologist and physiologist Robert Edwards and the nurse Jean ...
and embryologist
Jean Purdy
Jean Marian Purdy (25 April 1945 – 16 March 1985) was a British nurse and embryologist and a pioneer of fertility treatment. Purdy was responsible with Robert Edwards and Patrick Steptoe for developing in vitro fertilisation. Louise Joy Brow ...
but the latter two were not eligible for consideration as they had died and the Nobel Prize is not awarded posthumously.
With
egg donation
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
and IVF, women who are past their reproductive years, have infertile partners, have idiopathic female-fertility issues, or have reached
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
can still become pregnant. After the IVF treatment, some couples get pregnant without any fertility treatments. In 2018, it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques. A 2019 study that explores 10 adjuncts with IVF (screening hysteroscopy, DHEA, testosterone, GH, aspirin, heparin, antioxidants in males and females, seminal plasma, and PRP) suggests that until more evidence is done to show that these adjuncts are safe and effective, they should be avoided.
Terminology
The Latin term
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
, meaning "in glass", is used because early biological experiments involving cultivation of tissues outside the living organism were carried out in glass containers, such as beakers, test tubes, or Petri dishes. Today, the scientific term "in vitro" is used to refer to any biological procedure that is performed outside the organism in which it would normally have occurred, to distinguish it from an
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
procedure (such as in vivo fertilisation), where the tissue remains inside the living organism in which it is normally found.
A colloquial term for babies conceived as the result of IVF, "test tube babies", refers to the tube-shaped containers of glass or plastic resin, called
test tube
A test tube, also known as a culture tube or sample tube, is a common piece of laboratory glassware consisting of a finger-like length of glass or clear plastic tubing, open at the top and closed at the bottom.
Test tubes are usually placed in s ...
s, that are commonly used in chemistry and biology labs. However, IVF is usually performed in
Petri dish
A Petri dish (alternatively known as a Petri plate or cell-culture dish) is a shallow transparent lidded dish that biologists use to hold growth medium in which cells can be cultured,R. C. Dubey (2014): ''A Textbook Of Biotechnology For Class- ...
es, which are both wider and shallower and often used to cultivate cultures.
In a broader sense, IVF is a form of
assisted reproductive technology
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
(ART).
Medical uses
Indications
IVF may be used to overcome
female infertility
Female infertility refers to infertility in women. It affects an estimated 48 million women, with the highest prevalence of infertility affecting women in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Cen ...
when it is due to problems with the
fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s, making in vivo fertilisation difficult. It can also assist in
male infertility
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, ...
, in those cases where there is a defect in
sperm quality
Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality
Cryptorchidism, hypospadias, testicular cancer and poor semen quality ma ...
; in such situations
intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of emb ...
(ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg. In these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF.
According to UK's
National Institute for Health and Care Excellence
The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas:
* the use of health technologies withi ...
anovulation
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulat ...
, it may be an alternative after 7–12 attempted cycles of
ovulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles Ovulation Induction Retrieved on Mars 7, 2010 to reverse anovulation or oligoovulation.
Scop ...
, since the latter is expensive and more easy to control.
Success rates
IVF success rates are the percentage of all IVF procedures that result in favourable outcomes. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the
pregnancy rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
, or the number of live births, called the
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
. The success rate depends on variable factors such as maternal age, cause of infertility, embryo status, reproductive history, and lifestyle factors.
Maternal age: Younger candidates of IVF are more likely to get pregnant. Females older than 41 are more likely to get pregnant with a donor egg.
Reproductive history: women who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.
Due to advances in reproductive technology, live birth rates by cycle five of IVF have increased from 76% in 2005 to 80% in 2010 despite a reduction in the number of embryos being transferred (which decreased the multiple birth rate from 25% to 8%).
Live birth rate
The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include
miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
or
stillbirth
Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
; multiple-order births, such as twins and triplets, are counted as one pregnancy. A 2019 summary compiled by the Society for Assisted Reproductive Technology (SART) which reports the average IVF success rates in the United States per age group using non-donor eggs compiled the following data:
In 2006, Canadian clinics reported a live birth rate of 27%. Birth rates in younger patients were slightly higher, with a success rate of 35.3% for those 21 and younger, the youngest group evaluated. Success rates for older patients were also lower and decrease with age, with 37-year-olds at 27.4% and no live births for those older than 48, the oldest group evaluated. Some clinics exceeded these rates, but it is impossible to determine if that is due to superior technique or patient selection, since it is possible to artificially increase success rates by refusing to accept the most difficult patients or by steering them into oocyte donation cycles (which are compiled separately). Further, pregnancy rates can be increased by the placement of several embryos at the risk of increasing the chance for multiples.
Because not each IVF cycle that is started will lead to oocyte retrieval or embryo transfer, reports of live birth rates need to specify the denominator, namely IVF cycles started, IVF retrievals, or embryo transfers. The SART summarised 2008–9 success rates for US clinics for fresh embryo cycles that did not involve donor eggs and gave live birth rates by the age of the prospective mother, with a peak at 41.3% per cycle started and 47.3% per embryo transfer for patients under 35 years of age.
IVF attempts in multiple cycles result in increased cumulative live birth rates. Depending on the demographic group, one study reported 45% to 53% for three attempts, and 51% to 71% to 80% for six attempts.
Effective from 15 February 2021 the majority of Australian IVF clinics publish their individual success rate online via YourIVFSuccess.com.au. This site also contains a predictor tool.
Pregnancy rate
Pregnancy rate may be defined in various ways. In the United States, SART and the
Centers for Disease Control
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(and appearing in the table in the Success Rates section above) include statistics on positive pregnancy test and clinical pregnancy rate.
The 2019 summary compiled by the SART the following data for non-donor eggs (first embryo transfer) in the United States:
In 2006, Canadian clinics reported an average pregnancy rate of 35%.Branswell, Helen (15 December 2008 Success rate climbs for in vitro fertilisation The Canadian Press. A French study estimated that 66% of patients starting IVF treatment finally succeed in having a child (40% during the IVF treatment at the centre and 26% after IVF discontinuation). Achievement of having a child after IVF discontinuation was mainly due to
adoption
Adoption is a process whereby a person assumes the parenting of another, usually a child, from that person's biological or legal parent or parents. Legal adoptions permanently transfer all rights and responsibilities, along with filiation, from ...
(46%) or
spontaneous pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but can ...
(42%).
Miscarriage rate
According to a study done by the
Mayo Clinic
The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...
miscarriage rates for IVF are somewhere between 15 and 25%.
Predictors of success
The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be
maternal age
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.bFSH and number of oocytes, all reflecting ovarian function. Optimal woman's age is 23–39 years at time of treatment.
Biomarkers
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
that affect the pregnancy chances of IVF include:
*
Antral follicle count
An antral follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis.
Definitions differ in where the shift into an antral follicle occurs in the staging of follicul ...
, with higher count giving higher success rates.
*
Anti-Müllerian hormone
Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differen ...
levels, with higher levels indicating higher chances of pregnancy, as well as of live birth after IVF, even after adjusting for age.
* Level of
DNA fragmentation
DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be done intentionally by laboratory personnel or by cells, or can occur spontaneously. Spontaneous or accidental DNA fragmentation is fragmentation that gradually a ...
as measured, e.g. by
Comet assay
A comet is an icy, small Solar System body that, when passing close to the Sun, warms and begins to release gases, a process that is called outgassing. This produces a visible atmosphere or coma, and sometimes also a tail. These phenomena are ...
,
advanced maternal age
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.semen quality
Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality
Cryptorchidism, hypospadias, testicular cancer and poor semen quality ma ...
.
* Women with ovary-specific
FMR1
''FMR1'' (Fragile X Messenger Ribonucleoprotein 1) is a human gene that codes for a protein called ''fragile X messenger ribonucleoprotein'', or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development ...
genotypes including ''het-norm/low'' have significantly decreased pregnancy chances in IVF.
*
Progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
elevation on the day of
induction of final maturation Induction of final maturation of oocytes is a procedure that is usually performed as part of controlled ovarian hyperstimulation to render the oocytes fully developed and thereby resulting in optimal pregnancy chances. It is basically a replacement ...
is associated with lower pregnancy rates in IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins. At this time, compared to a progesterone level below 0.8 ng/ml, a level between 0.8 and 1.1 ng/ml confers an
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
of pregnancy of approximately 0.8, and a level between 1.2 and 3.0 ng/ml confers an odds ratio of pregnancy of between 0.6 and 0.7. On the other hand, progesterone elevation does not seem to confer a decreased chance of pregnancy in frozen–thawed cycles and cycles with egg donation.
* Characteristics of cells from the
cumulus oophorus
The cumulus oophorus, (discus proligerus), is a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation. In the antral follicle, it may be regarded as an extension of the membrana granulosa. The innermost layer ...
and the
membrana granulosa
The larger ovarian follicles
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to ...
, which are easily aspirated during
oocyte retrieval Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from the ovary of a woman, enabling fertilization outside the body. Transvaginal oocyt ...
. These cells are closely associated with the oocyte and share the same microenvironment, and the rate of expression of certain genes in such cells are associated with higher or lower pregnancy rate.
* An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.
Other
determinants
In mathematics, the determinant is a scalar value that is a function of the entries of a square matrix. It characterizes some properties of the matrix and the linear map represented by the matrix. In particular, the determinant is nonzero if and ...
of outcome of IVF include:
* As the maternal age increases, the likelihood of conception decreases and the chance of miscarriage increases.
*With increasing paternal age, especially 50 years and older, the rate of
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
formation decreases.
*
Tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
body mass index
Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
(BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27. Also, pregnant females who are obese have higher rates of
miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
,
gestational diabetes
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
,
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
thromboembolism
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
and problems during delivery, as well as leading to an increased risk of fetal
congenital abnormality
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
. Ideal body mass index is 19–30.
*
Salpingectomy
Salpingectomy refers to the surgical removal of a Fallopian tube. This may be done to treat an ectopic pregnancy or cancer, to prevent cancer, or as a form of contraception.
This procedure is now sometimes preferred over its ovarian tube-sparin ...
or
laparoscopic
Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
tubal occlusion before IVF treatment increases chances for women with
hydrosalpinges
A hydrosalpinx is a condition that occurs when a Fallopian tube is blocked and fills with serous or clear fluid near the ovary (distal to the uterus). The blocked tube may become substantially distended giving the tube a characteristic sausage-li ...
.Nice.org
* Success with previous pregnancy and/or live birth increases chances
* Low alcohol/caffeine intake increases success rate
* The number of embryos transferred in the treatment cycleFactors affecting IVF success – February 2011 from IVF-infertility.com
*
Embryo quality
Embryo quality is the ability of an embryo to perform successfully in terms of conferring a high pregnancy rate and/or resulting in a healthy person. Embryo profiling is the estimation of embryo quality by qualification and/or quantification of va ...
* Some studies also suggest that
autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
may also play a role in decreasing IVF success rates by interfering with the proper implantation of the embryo after transfer.
Aspirin is sometimes prescribed to women for the purpose of increasing the chances of conception by IVF, but there was no evidence to show that it is safe and effective.
A 2013
review
A review is an evaluation of a publication, product, service, or company or a critical take on current affairs in literature, politics or culture. In addition to a critical evaluation, the review's author may assign the work a content rating, ...
and
meta analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of
randomised controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s of
acupuncture
Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...
as an
adjuvant therapy
Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in ...
in IVF found no overall benefit, and concluded that an apparent benefit detected in a subset of published trials where the control group (those not using acupuncture) experienced a lower than average rate of pregnancy requires further study, due to the possibility of
publication bias
In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance o ...
and other factors.
A
Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
came to the result that endometrial injury performed in the month prior to ovarian induction appeared to increase both the live birth rate and clinical pregnancy rate in IVF compared with no endometrial injury. There was no evidence of a difference between the groups in miscarriage, multiple pregnancy or bleeding rates. Evidence suggested that endometrial injury on the day of oocyte retrieval was associated with a lower live birth or ongoing pregnancy rate.
Intake of
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s (such as
N-acetyl-cysteine
Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
,
melatonin
Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates ...
,
vitamin A
Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...
,
vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
,
vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...
,
folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
,
myo-inositol
Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and ...
,
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
or
selenium
Selenium is a chemical element with the symbol Se and atomic number 34. It is a nonmetal (more rarely considered a metalloid) with properties that are intermediate between the elements above and below in the periodic table, sulfur and tellurium, ...
) has not been associated with a significantly increased
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
or clinical
pregnancy rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
in IVF according to
Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
s. The review found that oral antioxidants given to men in couples with male factor or unexplained subfertility may improve live birth rates, but more evidence is needed.
A
Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
in 2015 came to the result that there is no evidence identified regarding the effect of preconception lifestyle advice on the chance of a live birth outcome.
Complications
Multiple births
The major complication of IVF is the risk of
multiple birth
A multiple birth is the culmination of one multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such bir ...
s. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss,
obstetrical complications
Complications of pregnancy are health problems that are related to pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are termed puerperal di ...
, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of less than . There is some evidence that making a double embryo transfer during one cycle achieves a higher live birth rate than a single embryo transfer; but making two single embryo transfers in two cycles has the same live birth rate and would avoid multiple pregnancies.
Sex ratio distortions
Certain kinds of IVF, in particular
ICSI ICSI may refer to:
* Intracytoplasmic sperm injection, a medical technique used in assisted reproduction
* International Computer Science Institute, a non-profit research lab in Berkeley, California
* Institute of Company Secretaries of India, a pr ...
(first applied in 1991) and
blastocyst transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizatio ...
(first applied in 1984) have been shown to lead to distortions in the
sex ratio
The sex ratio (or gender ratio) is usually defined as the ratio of males to females in a population. As explained by Fisher's principle, for evolutionary reasons this is typically about 1:1 in species which reproduce sexually. Many species devia ...
at birth. ICSI leads to slightly more female births (51.3% female) while blastocyst transfer leads to significantly more male births (56.1% male). Standard IVF done at the second or third day leads to a normal sex ratio.
Epigenetic modifications caused by extended culture leading to the death of more female embryos has been theorised as the reason why blastocyst transfer leads to a higher male sex ratio, however adding retinoic acid to the culture can bring this ratio back to normal.
Spread of infectious disease
By
sperm washing Sperm washing is the process in which individual sperms are separated from the semen. Washed sperm is used in artificial insemination using the intrauterine insemination (IUI) technique and in in vitro fertilization (IVF). It may also be used to d ...
, the risk that a chronic disease in the individual providing the sperm would infect the female or offspring can be brought to negligible levels.
In males with
hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. Fo ...
, The Practice Committee of the American Society for Reproductive Medicine advises that sperm washing is not necessary in IVF to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of
vertical transmission Vertical transmission of symbionts is the transfer of a microbial symbiont from the parent directly to the offspring. Many metazoan species carry symbiotic bacteria which play a mutualistic, commensal, or parasitic role. A symbiont is acquire ...
during IVF is no different from the risk in spontaneous conception. However, there is not enough evidence to say that
ICSI ICSI may refer to:
* Intracytoplasmic sperm injection, a medical technique used in assisted reproduction
* International Computer Science Institute, a non-profit research lab in Berkeley, California
* Institute of Company Secretaries of India, a pr ...
procedures are safe in females with hepatitis B in regard to vertical transmission to the offspring.
Regarding potential spread of
HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
, Japan's government prohibited the use of IVF procedures for couples in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the
Ogikubo, Tokyo
is a suburban, residential area of Tokyo in Suginami ward, approximately 8 km west of Shinjuku. Ogikubo has the Ogikubo Station on the JR Chūō Line (Rapid), the JR Chūō-Sōbu Line, the Tokyo Metro Marunouchi Line (terminus) and the To ...
Hospital, located in Tokyo, to use IVF for couples with HIV, the
Ministry of Health, Labour and Welfare
The is a cabinet level ministry of the Japanese government. It is commonly known as in Japan. The ministry provides services on health, labour and welfare.
It was formed with the merger of the former Ministry of Health and Welfare or and the ...
of Japan decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove HIV from sperm.
Other risks to the egg provider/retriever
A risk of ovarian stimulation is the development of
ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in very rare cases. Most cases are mild, but rarely the condition is severe and c ...
, particularly if hCG is used for inducing final oocyte maturation. This results in swollen, painful ovaries. It occurs in 30% of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalisation.
During egg retrieval, there exists a small chance of bleeding, infection, and damage to surrounding structures such as bowel and bladder (transvaginal ultrasound aspiration) as well as difficulty in breathing, chest infection, allergic reactions to medication, or nerve damage (laparoscopy).
Ectopic pregnancy
Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...
may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the fetus.
IVF does not seem to be associated with an elevated risk of
cervical cancer
Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
, nor with
ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
or
endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
when neutralising the
confounder
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
of infertility itself. Nor does it seem to impart any increased risk for
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
.
Regardless of pregnancy result, IVF treatment is usually stressful for patients.
Neuroticism
In the study of psychology, neuroticism has been considered a fundamental personality trait. For example, in the Big Five approach to personality trait theory, individuals with high scores for neuroticism are more likely than average to be moody ...
and the use of escapist coping strategies are associated with a higher degree of distress, while the presence of social support has a relieving effect. A negative pregnancy test after IVF is associated with an increased risk for depression in women, but not with any increased risk of developing
anxiety disorders
Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
. Pregnancy test results do not seem to be a risk factor for depression or anxiety among men.
Studies show that there is an increased risk of
venous thrombosis
Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...
or
pulmonary embolism
Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
during the first trimester of IVF. When looking at long-term studies comparing women who received or did not receive IVF, there seems to be no correlation with increased risk of cardiac events. There are more ongoing studies to solidify this.
Spontaneous pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but can ...
has occurred after successful and unsuccessful IVF treatments. Within 2 years of delivering an infant conceived through IVF, subfertile couples had a conception rate of 18%.
Birth defects
A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a
relative risk
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
of birth defects of 1.32 (95%
confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
1.24–1.42) compared to naturally conceived infants. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably
septal heart defect
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
s,
cleft lip
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
with or without
cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
,
esophageal atresia Esophageal can refer to:
* The esophagus
* Esophageal arteries
* Esophageal glands
The esophageal glands are glands that are part of the digestive system of various animals, including humans.
In humans
Esophageal glands in humans are a part of a ...
, and
anorectal atresia
An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknow ...
; the mechanism of causality is unclear. However, in a population-wide cohort study of 308,974 births (with 6,163 using assisted reproductive technology and following children from birth to age five) researchers found: "The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors." Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. The authors also found that a history of infertility elevated risk itself in the absence of any treatment (odds ratio 1.29), consistent with a Danish national registry study and "implicates patient factors in this increased risk." The authors of the Danish national registry study speculate: "our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants."
Other risks to the offspring
If the underlying infertility is related to abnormalities in
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...
, it is plausible, but too early to examine that male offspring are at higher risk for sperm abnormalities.
IVF does not seem to confer any risks regarding cognitive development, school performance, social functioning, and behaviour. Also, IVF infants are known to be as securely attached to their parents as those who were naturally conceived, and IVF adolescents are as well-adjusted as those who have been naturally conceived.
Limited long-term follow-up data suggest that IVF may be associated with an increased incidence of
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
impaired fasting glucose
Impaired fasting glucose is a type of prediabetes, in which a person's blood sugar levels during fasting are consistently above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. Together with impaired ...
, increase in total
body fat
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular en ...
composition, advancement of
bone age Bone age is the degree of a person's skeletal development. In children, bone age serves as a measure of physiological maturity and aids in the diagnosis of growth abnormalities, endocrine disorders, and other medical conditions. As a person grows fr ...
, subclinical
thyroid disorder
Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning ...
, early adulthood
clinical depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
and
binge drinking
Binge drinking, or heavy episodic drinking, is drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time, but definitions ( see below) vary considerably.
Binge drinking ...
in the offspring. It is not known, however, whether these potential associations are caused by the IVF procedure in itself, by adverse obstetric outcomes associated with IVF, by the genetic origin of the children or by yet unknown IVF-associated causes. Increases in embryo manipulation during IVF result in more deviant fetal growth curves, but birth weight does not seem to be a reliable marker of fetal stress.
IVF, including
ICSI ICSI may refer to:
* Intracytoplasmic sperm injection, a medical technique used in assisted reproduction
* International Computer Science Institute, a non-profit research lab in Berkeley, California
* Institute of Company Secretaries of India, a pr ...
Angelman syndrome
Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no f ...
), with an
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
of 3.7 (95%
confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
1.4 to 9.7).
An IVF-associated incidence of
cerebral palsy
Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sensa ...
and
neurodevelopmental delay
Developmental disability is a diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood. Developmental disabilities cause individuals living with them many difficulties in certain areas of life, espe ...
are believed to be related to the
confounder
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
s of prematurity and low birthweight. Similarly, an IVF-associated incidence of
autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
and
attention-deficit disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
are believed to be related to confounders of maternal and obstetric factors.
Overall, IVF does not cause an increased risk of
childhood cancer
Childhood cancer is cancer in a child. About 80% of childhood cancer cases can be successfully treated thanks to modern medical treatments and optimal patient care. However, only about 10% of children diagnosed with cancer reside in high-income cou ...
. Studies have shown a decrease in the risk of certain cancers and an increased risks of certain others including
retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...
,
hepatoblastoma
Hepatoblastoma is a malignant liver cancer occurring in infants and children and composed of tissue resembling fetal liver cells, mature liver cells, or bile duct cells. They usually present with an abdominal mass. The disease is most commonly di ...
and
rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.
There are four subt ...
.
Method
Theoretically, IVF could be performed by collecting the contents from the fallopian tubes or uterus after natural ovulation, mixing it with
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
, and reinserting the fertilised ova into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. The additional techniques that are routinely used in IVF include ovarian hyperstimulation to generate multiple eggs, ultrasound-guided
transvaginal oocyte retrieval Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from the ovary of a woman, enabling fertilization outside the body. Transvaginal oocy ...
directly from the ovaries, co-incubation of eggs and sperm, as well as culture and selection of resultant embryos before
embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizati ...
into a uterus.
Ovarian hyperstimulation
Ovarian hyperstimulation is the stimulation to induce development of multiple follicles of the ovaries. It should start with response prediction by e.g. age,
antral follicle count
An antral follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis.
Definitions differ in where the shift into an antral follicle occurs in the staging of follicul ...
and level of
anti-Müllerian hormone
Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differen ...
. The resulting prediction of e.g. poor or hyper-response to ovarian hyperstimulation determines the protocol and dosage for ovarian hyperstimulation.
Ovarian hyperstimulation also includes suppression of spontaneous ovulation, for which two main methods are available: Using a (usually longer)
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
protocol or a (usually shorter)
GnRH antagonist
Gonadotropin-releasing hormone antagonists (GnRH antagonists) are a class of medications that receptor antagonist, antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH ...
protocol. In a standard long GnRH agonist protocol the day when hyperstimulation treatment is started and the expected day of later oocyte retrieval can be chosen to conform to personal choice, while in a GnRH antagonist protocol it must be adapted to the spontaneous onset of the previous menstruation. On the other hand, the GnRH antagonist protocol has a lower risk of
ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in very rare cases. Most cases are mild, but rarely the condition is severe and c ...
(OHSS), which is a life-threatening complication.
For the ovarian hyperstimulation in itself, injectable
gonadotropin
Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chorioni ...
s (usually FSH analogues) are generally used under close monitoring. Such monitoring frequently checks the
estradiol
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
level and, by means of
gynecologic ultrasonography
Gynecologic ultrasonography or gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs (specifically the uterus, the ovaries, and the fallopian tubes) as well as the bladder, the adnexa, and the re ...
, follicular growth. Typically approximately 10 days of injections will be necessary.
Natural IVF
There are several methods termed ''natural cycle IVF'':
* IVF using no drugs for ovarian hyperstimulation, while drugs for
ovulation suppression Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by Transvaginal oocyte retrieval ...
may still be used.
* IVF using ovarian hyperstimulation, including gonadotropins, but with a
GnRH antagonist
Gonadotropin-releasing hormone antagonists (GnRH antagonists) are a class of medications that receptor antagonist, antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH ...
protocol so that the cycle initiates from natural mechanisms.
*
Frozen embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizatio ...
embryo cryopreservation
Cryopreservation of embryos is the process of Cryopreservation, preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.
Indications
...
, followed by
embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizati ...
in a later, natural, cycle.
IVF using no drugs for ovarian hyperstimulation was the method for the conception of
Louise Brown
Louise Joy Brown (born 25 July 1978) is an English woman who was the first human to have been born after conception by ''in vitro'' fertilisation experiment (IVF). Her birth, following a procedure pioneered in Britain, has been lauded among "t ...
. This method can be successfully used when women want to avoid taking ovarian stimulating drugs with its associated side-effects.
HFEA
The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the Unite ...
has estimated the
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
to be approximately 1.3% per IVF cycle using no hyperstimulation drugs for women aged between 40 and 42.
Mild IVF is a method where a small dose of ovarian stimulating drugs are used for a short duration during a natural menstrual cycle aimed at producing 2–7 eggs and creating healthy embryos. This method appears to be an advance in the field to reduce complications and side-effects for women, and it is aimed at quality, and not quantity of eggs and embryos. One study comparing a mild treatment (mild ovarian stimulation with GnRH antagonist co-treatment combined with
single embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizatio ...
) to a standard treatment (stimulation with a
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
long-protocol and transfer of two embryos) came to the result that the proportions of cumulative pregnancies that resulted in term live birth after 1 year were 43.4% with mild treatment and 44.7% with standard treatment. Mild IVF can be cheaper than conventional IVF and with a significantly reduced risk of
multiple gestation
A multiple birth is the culmination of one multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such bir ...
When the ovarian follicles have reached a certain degree of development, induction of final oocyte maturation is performed, generally by an injection of
human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG). Commonly, this is known as the "trigger shot." hCG acts as an analogue of
luteinising hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
, and ovulation would occur between 38 and 40 hours after a single HCG injection, but the egg retrieval is performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. This avails for scheduling the egg retrieval procedure at a time where the eggs are fully mature. HCG injection confers a risk of
ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in very rare cases. Most cases are mild, but rarely the condition is severe and c ...
. Using a
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
instead of hCG eliminates most of the risk of ovarian hyperstimulation syndrome, but with a reduced delivery rate if the embryos are transferred fresh. For this reason, many centers will freeze all oocytes or embryos following agonist trigger.
Egg retrieval
The eggs are retrieved from the patient using a transvaginal technique called
transvaginal oocyte retrieval Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from the ovary of a woman, enabling fertilization outside the body. Transvaginal oocy ...
, involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. Through this needle follicles can be aspirated, and the follicular fluid is passed to an embryologist to identify ova. It is common to remove between ten and thirty eggs. The retrieval procedure usually takes between 20 and 40 minutes, depending on the number of mature follicles, and is usually done under
conscious sedation
Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decr ...
or
general anaesthesia
General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...
.
Egg and sperm preparation
In the laboratory, for ICSI treatments, the identified eggs are stripped of surrounding cells (also known as
cumulus cell
The cumulus oophorus, (discus proligerus), is a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation. In the antral follicle, it may be regarded as an extension of the membrana granulosa. The innermost layer o ...
s) and prepared for
fertilisation
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
. An
oocyte selection Oocyte selection is a procedure that is performed prior to in vitro fertilization, in order to use oocytes with maximal chances of resulting in pregnancy. In contrast, embryo selection takes place ''after'' fertilization.
__TOC__ Techniques
Chromoso ...
may be performed prior to fertilisation to select eggs that can be fertilised, as it is required they are in metaphase II. There are cases in which if oocytes are in the metaphase I stage, they can be kept being cultured so as to undergo a posterior sperm injection. In the meantime,
semen
Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
is prepared for fertilisation by removing inactive cells and seminal fluid in a process called
sperm washing Sperm washing is the process in which individual sperms are separated from the semen. Washed sperm is used in artificial insemination using the intrauterine insemination (IUI) technique and in in vitro fertilization (IVF). It may also be used to d ...
. If semen is being provided by a
sperm donor
Sperm donation is the provision by a man of his sperm with the intention that it be used in the artificial insemination or other 'fertility treatment' of a woman or women who are not his sexual partners in order that they may become pregnant by hi ...
, it will usually have been prepared for treatment before being frozen and quarantined, and it will be thawed ready for use.
Co-incubation
The sperm and the egg are incubated together at a ratio of about 75,000:1 in a
culture media
A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Different ...
in order for the actual
fertilisation
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
to take place. A review in 2013 came to the result that a duration of this co-incubation of about 1 to 4 hours results in significantly higher
pregnancy rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
s than 16 to 24 hours. In most cases, the egg will be fertilised during co-incubation and will show two
pronuclei
A pronucleus () is the nucleus of a sperm or egg cell during the process of fertilization. The sperm cell becomes a pronucleus after the sperm enters the ovum, but before the genetic material of the sperm and egg fuse. Contrary to the sperm cell, ...
. In certain situations, such as low sperm count or motility, a single sperm may be injected directly into the egg using
intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of emb ...
(ICSI). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg consists of six to eight cells.
In
gamete intrafallopian transfer
Gamete intrafallopian transfer (GIFT) is a tool of assisted reproductive technology against infertility. Eggs are removed from a woman's ovaries, and placed in one of the Fallopian tubes, along with the man's sperm. The technique, first attem ...
, eggs are removed from the woman and placed in one of the fallopian tubes, along with the man's sperm. This allows fertilisation to take place inside the woman's body. Therefore, this variation is actually an in vivo fertilisation, not in vitro.
Embryo culture
The main durations of embryo culture are until
cleavage stage
In embryology, cleavage is the division of cells in the early development of the embryo, following fertilization. The zygotes of many species undergo rapid cell cycles with no significant overall growth, producing a cluster of cells the same size ...
(day two to four after
co-incubation
In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
) or the
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
stage (day five or six after
co-incubation
In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
). Embryo culture until the blastocyst stage confers a significant increase in
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
per
embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique (which is often used in connection with in vitro fertilizati ...
, but also confers a decreased number of embryos available for transfer and
embryo cryopreservation
Cryopreservation of embryos is the process of Cryopreservation, preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.
Indications
...
, so the cumulative clinical pregnancy rates are increased with cleavage stage transfer. Transfer day two instead of day three after fertilisation has no differences in
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
. There are significantly higher odds of
preterm birth
Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 we ...
(
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
1.3) and
congenital anomalies
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
(
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
1.3) among births having from embryos cultured until the blastocyst stage compared with cleavage stage.
Embryo selection
Laboratories have developed grading methods to judge ovocyte and
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
quality. In order to optimise
pregnancy rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
s, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos. Since 2009 where the first
time-lapse microscopy
Time-lapse microscopy is time-lapse photography applied to microscopy.
Microscope image sequences are recorded and then viewed at a greater speed to
give an accelerated view of the microscopic process.
Before the introduction of the video tape ...
system for IVF was approved for clinical use, morphokinetic scoring systems has shown to improve to
pregnancy rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
s further. However, when all different types of
time-lapse embryo imaging Time-lapse embryo imaging is an emerging non-invasive embryo selection technique used in reproductive biology. It is used to help select embryos with lower risk of defects and/or greater potential of implantation. The procedure involves taking thou ...
devices, with or without morphokinetic scoring systems, are compared against conventional embryo assessment for IVF, there is insufficient evidence of a difference in live-birth, pregnancy, stillbirth or miscarriage to choose between them. Active efforts to develop a more accurate embryo selection analysis based on Artificial Intelligence and Deep Learning are underway. Embryo Ranking Intelligent Classification Assistant (ERICA), is a clear example. This Deep Learning software substitutes manual classifications with a ranking system based on an individual embryo's predicted genetic status in a non-invasive fashion. Studies on this area are still pending and current feasibility studies support its potential.
Embryo transfer
The number to be transferred depends on the number available, the age of the patient and other health and diagnostic factors. In countries such as Canada, the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. In the UK and according to
HFEA
The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the Unite ...
regulations, a woman over 40 may have up to three embryos transferred, whereas in the US, there is no legal limit on the number of embryos which may be transferred, although medical associations have provided practice guidelines. Most clinics and country regulatory bodies seek to minimise the risk of multiple pregnancy, as it is not uncommon for multiple embryos to implant if multiple embryos are transferred. Embryos are transferred to the patient's uterus through a thin, plastic
catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
, which goes through her
vagina
In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy.
Luteal support
Luteal support Luteal support is the administration of medication, generally progesterone, progestins, hCG or GnRH agonists, to increase the success rate of implantation and early embryogenesis, thereby complementing and/or supporting the function of the corpus ...
is the administration of medication, generally
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
,
progestin
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
s, hCG, or
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
s, and often accompanied by estradiol, to increase the success rate of implantation and early
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, thereby complementing and/or supporting the function of the
corpus luteum
The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
. A Cochrane review found that hCG or progesterone given during the luteal phase may be associated with higher rates of live birth or ongoing pregnancy, but that the evidence is not conclusive. Co-treatment with
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
s appears to improve outcomes, by a live birth rate RD of +16% (95%
confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
+10 to +22%). On the other hand,
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
or
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
as adjunctive medication in IVF have no evidence of overall benefit.
Expansions
There are various expansions or additional techniques that can be applied in IVF, which are usually not necessary for the IVF procedure itself, but would be virtually impossible or technically difficult to perform without concomitantly performing methods of IVF.
Preimplantation genetic screening or diagnosis
Preimplantation genetic screening
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
(PGS) or preimplantation genetic diagnosis (PGD) has been suggested to be able to be used in IVF to select an embryo that appears to have the greatest chances for successful pregnancy. However, a systematic review and meta-analysis of existing
randomised controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s came to the result that there is no evidence of a beneficial effect of PGS with cleavage-stage biopsy as measured by
live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple ...
. On the contrary, for women of
advanced maternal age
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.mosaicism
Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized e ...
are the major underlying factors for inefficacy of PGS.
Still, as an expansion of IVF, patients who can benefit from PGS/PGD include:
* Couples who have a family history of inherited disease
* Couples who want
prenatal sex discernment
Prenatal sex discernment is the prenatal testing for discerning the sex of a fetus before birth.
Methods
Prenatal sex discernment can be performed by preimplantation genetic diagnosis before conception, but this method may not always be classif ...
. This can be used to diagnose
monogenic disorders
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
with
sex linkage
Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...
. It can potentially be used for
sex selection
Sex selection is the attempt to control the sex of the offspring to achieve a desired sex. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at childbirth. It has been marketed under the title family ...
, wherein a fetus is aborted if having an undesired sex.
* Couples who already have a child with an incurable disease and need compatible cells from a second healthy child to cure the first, resulting in a "
saviour sibling
A savior baby or savior sibling is a child who is conceived in order to provide a stem cell transplant to a sibling that is affected with a fatal disease, such as cancer or Fanconi anemia, that can best be treated by hematopoietic stem cell transp ...
" that matches the sick child in
HLA type
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
.
PGS screens for numeral chromosomal abnormalities while PGD diagnosis the specific molecular defect of the inherited disease. In both PGS and PGD, individual cells from a pre-embryo, or preferably trophectoderm cells biopsied from a
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
, are analysed during the IVF process. Before the transfer of a pre-embryo back to a woman's uterus, one or two cells are removed from the pre-embryos (8-cell stage), or preferably from a
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
. These cells are then evaluated for normality. Typically within one to two days, following completion of the evaluation, only the normal pre-embryos are transferred back to the woman's uterus. Alternatively, a blastocyst can be cryopreserved via vitrification and transferred at a later date to the uterus. In addition, PGS can significantly reduce the risk of multiple pregnancies because fewer embryos, ideally just one, are needed for implantation.
Cryopreservation
Cryopreservation
Cryo-preservation or cryo-conservation is a process where Organism, organisms, organelles, cell (biology), cells, Biological tissue, tissues, extracellular matrix, Organ (anatomy), organs, or any other biological constructs susceptible to damage ...
can be performed as
oocyte cryopreservation
Human oocyte cryopreservation (egg freezing) is a procedure to preserve a woman's eggs (oocytes). This technique has been used to enable women to postpone pregnancy to a later date – whether for medical reasons (such as cancer treatment), or fo ...
before fertilisation, or as
embryo cryopreservation
Cryopreservation of embryos is the process of Cryopreservation, preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.
Indications
...
after fertilisation.
The Rand Consulting Group has estimated there to be 400,000 frozen embryos in the United States in 2006. The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. Spare oocytes or embryos resulting from fertility treatments may be used for
oocyte donation
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
or
embryo donation Embryo donation is one disposition option for users of in vitro fertilisation with remaining fresh or frozen embryos. It is defined as the giving—generally without compensation—of embryos remaining after in vitro fertilization procedures to rec ...
to another woman or couple, and embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm. Also, oocyte cryopreservation can be used for women who are likely to lose their ovarian reserve due to undergoing
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
.
By 2017, many centers have adopted embryo cryopreservation as their primary IVF therapy, and perform few or no fresh embryo transfers. The two main reasons for this have been better endometrial receptivity when embryos are transferred in cycles without exposure to ovarian stimulation and also the ability to store the embryos while awaiting the results of preimplantation genetic testing.
The outcome from using cryopreserved embryos has uniformly been positive with no increase in birth defects or development abnormalities.
Other expansions
*
Intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of emb ...
(ICSI) is where a single
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
is injected directly into an
egg
An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...
. Its main usage as an expansion of IVF is to overcome male infertility problems, although it may also be used where eggs cannot easily be penetrated by sperm, and occasionally in conjunction with
sperm donation
Sperm donation is the provision by a man of his sperm with the intention that it be used in the artificial insemination or other 'fertility treatment' of a woman or women who are not his sexual partners in order that they may become pregnant by hi ...
. It can be used in
teratozoospermia
Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males.
Causes
The causes of teratozoospermia are unknown in most cases. However, Hodgkin's disease, coeliac ...
, since once the egg is fertilised abnormal sperm morphology does not appear to influence
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
development or blastocyst morphology.
* Additional methods of embryo profiling. For example, methods are emerging in making comprehensive analyses of up to entire
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s,
transcriptome
The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...
s,
proteome
The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
s and
metabolome
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The smal ...
s which may be used to score embryos by comparing the patterns with ones that have previously been found among embryos in successful versus unsuccessful pregnancies.
*
Assisted zona hatching
Assisted zona hatching (AZH) is a procedure of assisted reproductive technology in which a small hole is made in the zona pellucida, using a micromanipulator, thereby facilitating zona hatching. Zona hatching is where the blastocyst gets rid of the ...
(AZH) can be performed shortly before the embryo is transferred to the uterus. A small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo.
* In
egg donation
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
and
embryo donation Embryo donation is one disposition option for users of in vitro fertilisation with remaining fresh or frozen embryos. It is defined as the giving—generally without compensation—of embryos remaining after in vitro fertilization procedures to rec ...
, the resultant embryo after fertilisation is inserted in another woman than the one providing the eggs. These are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or
advanced maternal age
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.oocyte selection Oocyte selection is a procedure that is performed prior to in vitro fertilization, in order to use oocytes with maximal chances of resulting in pregnancy. In contrast, embryo selection takes place ''after'' fertilization.
__TOC__ Techniques
Chromoso ...
, the oocytes with optimal chances of live birth can be chosen. It can also be used as a means of
preimplantation genetic screening
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
.
* Embryo splitting can be used for twinning to increase the number of available embryos.
*
Cytoplasmic transfer
Mitochondrial replacement therapy (MRT), sometimes called mitochondrial donation, is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. MRT originated as a special form of in vitro fertilisation in which some or ...
is where the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
from a donor egg is injected into an egg with compromised
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. The resulting egg is then
fertilised
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
with
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
womb
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
, usually that of the woman who provided the recipient egg and
nuclear DNA
Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. It ...
. Cytoplasmic transfer was created to aid women who experience infertility due to deficient or damaged
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, contained within an egg's
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
.
Leftover embryos or eggs
There may be leftover embryos or eggs from IVF procedures if the woman for whom they were originally created has successfully carried one or more pregnancies to term, and no longer wishes to use them. With the woman's or couple's permission, these may be donated to help other women or couples as a means of
third party reproduction
Third-party reproduction or donor-assisted reproduction is any human reproduction in which DNA or gestation is provided by a third party or donor other than the one or two parents who will raise the resulting child. This goes beyond the traditio ...
.
In
embryo donation Embryo donation is one disposition option for users of in vitro fertilisation with remaining fresh or frozen embryos. It is defined as the giving—generally without compensation—of embryos remaining after in vitro fertilization procedures to rec ...
, these extra embryos are given to other couples or women for
transfer
Transfer may refer to:
Arts and media
* ''Transfer'' (2010 film), a German science-fiction movie directed by Damir Lukacevic and starring Zana Marjanović
* ''Transfer'' (1966 film), a short film
* ''Transfer'' (journal), in management studies
...
, with the goal of producing a successful pregnancy. Embryo recipients typically have genetic issues or poor-quality embryos or eggs of their own. The resulting child is considered the child of the woman who carries it and gives birth, and not the child of the donor, the same as occurs with
egg donation
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
or
sperm donation
Sperm donation is the provision by a man of his sperm with the intention that it be used in the artificial insemination or other 'fertility treatment' of a woman or women who are not his sexual partners in order that they may become pregnant by hi ...
.
Typically, genetic parents donate the eggs or embryos to a
fertility clinic
Fertility clinics are medical clinics that assist couples, and sometimes individuals, who want to become parents but for medical reasons have been unable to achieve this goal via the natural course. Clinics apply a number of diagnosis tests and s ...
where they are preserved by
oocyte cryopreservation
Human oocyte cryopreservation (egg freezing) is a procedure to preserve a woman's eggs (oocytes). This technique has been used to enable women to postpone pregnancy to a later date – whether for medical reasons (such as cancer treatment), or fo ...
or
embryo cryopreservation
Cryopreservation of embryos is the process of Cryopreservation, preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.
Indications
...
until a carrier is found for them. Typically the process of matching the donation with the prospective parents is conducted by the agency itself, at which time the clinic transfers ownership of the embryos to the prospective parents.
In the United States, women seeking to be an embryo recipient undergo infectious disease screening required by the
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA), and reproductive tests to determine the best placement location and cycle timing before the actual embryo transfer occurs. The amount of screening the embryo has already undergone is largely dependent on the genetic parents' own IVF clinic and process. The embryo recipient may elect to have her own
embryologist
Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, '' -logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos and ...
conduct further testing.
Alternatives to donating unused embryos are destroying them (or having them transferred at a time when pregnancy is very unlikely),Beil, Laura (1 September 2009 "What happens to extra embryos after IVF?" ''CNN''. keeping them frozen indefinitely, or donating them for use in research (which results in their unviability). Individual moral views on disposing of leftover embryos may depend on personal views on the
beginning of human personhood
The beginning of human personhood is the moment when a human is first recognized as a person. There are differences of opinion as to the precise time when human personhood begins and the nature of that status. The issue arises in a number of fi ...
and the definition and/or value of potential future persons, and on the value that is given to fundamental research questions. Some people believe donation of leftover embryos for research is a good alternative to discarding the embryos when patients receive proper, honest and clear information about the research project, the procedures and the scientific values.
History
The first successful birth of a child after IVF treatment,
Louise Brown
Louise Joy Brown (born 25 July 1978) is an English woman who was the first human to have been born after conception by ''in vitro'' fertilisation experiment (IVF). Her birth, following a procedure pioneered in Britain, has been lauded among "t ...
, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (now Dr Kershaw's Hospice) in
Royton
Royton is a town in the Metropolitan Borough of Oldham, Greater Manchester, England, with a population of 21,284 in 2011. Close to the source of the River Irk, near undulating land at the foothills of the South Pennines, it is northwest of Old ...
, Oldham, England.
Robert G. Edwards
Sir Robert Geoffrey Edwards (27 September 1925 – 10 April 2013) was a British physiologist and pioneer in reproductive medicine, and in-vitro fertilisation (IVF) in particular. Along with obstetrician and gynaecologist Patrick Steptoe ...
, the physiologist who co-developed the treatment, was awarded the
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
in 2010. His co-workers,
Patrick Steptoe
Patrick Christopher Steptoe CBE FRS (9 June 1913 – 21 March 1988) was an English obstetrician and gynaecologist and a pioneer of fertility treatment. Steptoe was responsible with biologist and physiologist Robert Edwards and the nurse Jean ...
and
Jean Purdy
Jean Marian Purdy (25 April 1945 – 16 March 1985) was a British nurse and embryologist and a pioneer of fertility treatment. Purdy was responsible with Robert Edwards and Patrick Steptoe for developing in vitro fertilisation. Louise Joy Brow ...
, were not eligible for consideration as the Nobel Prize is not awarded posthumously.
The second successful birth of a 'test tube baby' occurred in India just 67 days after Louise Brown was born. The girl, named Durga, was conceived in vitro using a method developed independently by Dr Subhash Mukhopadhyay, a physician and researcher from
Kolkata
Kolkata (, or , ; also known as Calcutta , the official name until 2001) is the capital of the Indian state of West Bengal, on the eastern bank of the Hooghly River west of the border with Bangladesh. It is the primary business, comme ...
. Mukhopadhyay had been performing experiments on his own with primitive instruments and a household refrigerator. However, state authorities prevented him from presenting his work at scientific conferences, and it was many years before Mukhopadhyay's contribution was acknowledged in works dealing with the subject.
With
egg donation
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
and IVF, women who are past their reproductive years, have infertile male partners, have idiopathic female-fertility issues, or have reached
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
can still become pregnant.
Adriana Iliescu
Adriana Iliescu (born 31 May 1938) is a Romanian retired university teacher, philologist and author of children's novels. She received international media attention in 2005, when she gave birth to daughter Eliza at age 66, making her the oldest ...
held the record as the oldest woman to give birth using IVF and a donor egg, when she gave birth in 2004 at the age of 66, a record passed in 2006. After the IVF treatment some couples are able to get pregnant without any fertility treatments. In 2018 it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques.
Ethics
Mix-ups
In some cases, laboratory mix-ups (misidentified gametes, transfer of wrong embryos) have occurred, leading to legal action against the IVF provider and complex paternity suits. An example is the case of a woman in California who received the embryo of another couple and was notified of this mistake after the birth of her son. This has led to many authorities and individual clinics implementing procedures to minimise the risk of such mix-ups. The
HFEA
The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the Unite ...
, for example, requires clinics to use a double witnessing system, the identity of specimens is checked by two people at each point at which specimens are transferred. Alternatively, technological solutions are gaining favour, to reduce the manpower cost of manual double witnessing, and to further reduce risks with uniquely numbered
RFID
Radio-frequency identification (RFID) uses electromagnetic fields to automatically identify and track tags attached to objects. An RFID system consists of a tiny radio transponder, a radio receiver and transmitter. When triggered by an electromag ...
tags which can be identified by readers connected to a computer. The computer tracks specimens throughout the process and alerts the embryologist if non-matching specimens are identified. Although the use of RFID tracking has expanded in the US, it is still not widely adopted.
Preimplantation genetic diagnosis or screening
While PGD was originally designed to screen for embryos carrying hereditary genetic diseases, the method has been applied to select features that are unrelated to diseases, thus raising ethical questions. Examples of such cases include the selection of embryos based on
histocompatibility
Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many uni ...
(HLA) for the donation of tissues to a sick family member, the diagnosis of genetic susceptibility to disease, and
sex selection
Sex selection is the attempt to control the sex of the offspring to achieve a desired sex. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at childbirth. It has been marketed under the title family ...
.
These examples raise ethical issues because of the morality of
eugenics
Eugenics ( ; ) is a fringe set of beliefs and practices that aim to improve the genetic quality of a human population. Historically, eugenicists have attempted to alter human gene pools by excluding people and groups judged to be inferior or ...
. It becomes frowned upon because of the advantage of being able to eliminate unwanted traits and selecting desired traits. By using PGD, individuals are given the opportunity to create a human life unethically and rely on science and not by
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charle ...
.
For example, a deaf British couple, Tom and Paula Lichy, have petitioned to create a deaf baby using IVF. Some
medical ethicists
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practice ...
have been very critical of this approach.
Jacob M. Appel
Jacob M. Appel (born February 21, 1973) is an American author, poet, bioethicist, physician, lawyer and social critic.Nagamatsu, Sequoia "A Few Words with the Ubiquitous Jacob M. Appel" ''Prince Mincer'' Journal http://primemincer.com/ confirmed ...
wrote that "intentionally culling out blind or deaf embryos might prevent considerable future suffering, while a policy that allowed deaf or blind parents to select ''for'' such traits intentionally would be far more troublesome."
Profit desire of the industry
In 2008, a California physician transferred 12 embryos to a woman who gave birth to octuplets (
Suleman octuplets
The Suleman octuplets are six male and two female children conceived via in vitro fertilization (IVF) and subsequently born to Nadya Suleman on January 26, 2009, in Bellflower, California. Residing in Lancaster, California, they are the first kno ...
). This led to accusations that a doctor is willing to endanger the health and even life of people in order to gain money. Robert Winston, professor of fertility studies at Imperial College London, had called the industry "corrupt" and "greedy" stating that "one of the major problems facing us in healthcare is that IVF has become a massive commercial industry," and that "what has happened, of course, is that money is corrupting this whole technology", and accused authorities of failing to protect couples from exploitation: "The regulatory authority has done a consistently bad job. It's not prevented the exploitation of people, it's not put out very good information to couples, it's not limited the number of unscientific treatments people have access to". The IVF industry has been described as a market-driven construction of health, medicine and the human body.
In the US, the
Copyright Clause
The Copyright Clause (also known as the Intellectual Property Clause, Copyright and Patent Clause, or the Progress Clause) describes an enumerated power listed in the United States Constitution ( Article I, Section 8, Clause 8).
The clause, wh ...
provides innovators with a temporary monopoly over their respective work. As a result, IVF is prohibitively expensive for patients as providers have to also cover the costs of patents. For example,
23andMe
23andMe Holding Co. is a publicly held personal genomics and biotechnology company based in South San Francisco, California. It is best known for providing a direct-to-consumer genetic testing service in which customers provide a saliva sample t ...
has patented a process used to calculate the probability of gene inheritance.
The industry has been accused of making unscientific claims, and distorting facts relating to infertility, in particular through widely exaggerated claims about how common infertility is in society, in an attempt to get as many couples as possible and as soon as possible to try treatments (rather than trying to conceive naturally for a longer time). This risks removing infertility from its social context and reducing the experience to a simple biological malfunction, which not only ''can'' be treated through bio-medical procedures, but should be treated by them. Indeed, there are serious concerns about the overuse of treatments, for instance Dr Sami David, a fertility specialist, has expressed disappointment over the current state of the industry, and said many procedures are unnecessary; he said: "It's being the first choice of treatment rather than the last choice. When it was first opening up in late 1970s, early 80s, it was meant to be the last resort. Now it's a first resort. I think that it can harm women in the long run." IVF thus raises ethical issues concerning the abuse of bio-medical facts to 'sell' corrective procedures and treatments for conditions that deviate from a constructed ideal of the 'healthy' or 'normal' body i.e., fertile females and males with reproductive systems capable of co-producing offspring.
IVF over age 40
All pregnancies can be risky, but there are greater risk for women who are older and are over the age of 40. The older the woman the riskier the pregnancy. As women get older, they are more likely to develop conditions such as gestational diabetes and pre-eclampsia. If older women do conceive over the age of 40, their offspring may be of lower birth weight, and more likely to requires intensive care. Because of this, the increased risk is a sufficient cause for concern. The high incidence of caesarean in older mothers is commonly regarded as a risk.
Though there are some risk with older pregnancies, there are some benefits associated with caesareans. A study has shown that births over 40 have a lower rate of birth trauma due to increased delivery by caesarean. Though caesarean is seen to benefit mothers over 40, there are still many risk factors to consider. Caesarean section may be a risk in the same way that gestational diabetes is.
Women conceiving at 40 have a greater risk of gestational hypertension and premature birth. The offspring is at risk when being born from older mothers, and the risks associated with being conceived through IVF.
Adriana Iliescu
Adriana Iliescu (born 31 May 1938) is a Romanian retired university teacher, philologist and author of children's novels. She received international media attention in 2005, when she gave birth to daughter Eliza at age 66, making her the oldest ...
held the record for a while as the oldest woman to give birth using IVF and a donor egg, when she gave birth in 2004 at the age of 66. In September 2019, a 74-year-old woman became the oldest-ever to give birth after she delivered twins at a hospital in
Guntur
Guntur () is a city and the administrative headquarters of Guntur district in the Indian state of Andhra Pradesh. Guntur is spread across 168.49 km square and is the third-largest city in the state. It is situated to the west of the Ba ...
,
Andhra Pradesh
Andhra Pradesh (, abbr. AP) is a state in the south-eastern coastal region of India. It is the seventh-largest state by area covering an area of and tenth-most populous state with 49,386,799 inhabitants. It is bordered by Telangana to the ...
.
Pregnancy after menopause
Although menopause is a natural barrier to further conception, IVF has allowed women to be pregnant in their fifties and sixties. Women whose uteruses have been appropriately prepared receive embryos that originated from an egg of an egg donor. Therefore, although these women do not have a genetic link with the child, they have a physical link through pregnancy and
childbirth
Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births globall ...
. In many cases the genetic father of the child is the woman's partner. Even after menopause the uterus is fully capable of carrying out a pregnancy.
Same-sex couples, single and unmarried parents
A 2009 statement from the ASRM found no persuasive evidence that children are harmed or disadvantaged solely by being raised by single parents, unmarried parents, or homosexual parents. It did not support restricting access to assisted reproductive technologies on the basis of a prospective parent's marital status or sexual orientation. A 2018 study found that children's psychological well-being did not differ when raised by either same-sex parents or heterosexual parents, even finding that psychological well-being was better amongst children raised by same-sex parents.
Ethical concerns include reproductive rights, the welfare of offspring, nondiscrimination against unmarried individuals, homosexual, and professional autonomy.
A recent controversy in California focused on the question of whether physicians opposed to same-sex relationships should be required to perform IVF for a lesbian couple. Guadalupe T. Benitez, a lesbian medical assistant from San Diego, sued doctors Christine Brody and Douglas Fenton of the North Coast Woman's Care Medical Group after Brody told her that she had "religious-based objections to treating her and homosexuals in general to help them conceive children by artificial insemination," and Fenton refused to authorise a refill of her prescription for the fertility drug Clomid on the same grounds. The California Medical Association had initially sided with Brody and Fenton, but the case,
North Coast Women's Care Medical Group v. Superior Court
''North Coast Women's Care Medical Group, Inc. v. San Diego County Superior Court'' () is a case decided before the California Supreme Court on August 18, 2008, ruling that physicians must offer IUI infertility services to gays and lesbians despit ...
, was decided unanimously by the California State Supreme Court in favour of Benitez on 19 August 2008.Egelko, Bob (19 August 2008), "Bob Doctors can't use bias to deny gays treatment", ''San Francisco Chronicle''.
Nadya Suleman
Natalie Denise Suleman (born Nadya Denise Doud-Suleman; July 11, 1975), known as Octomom in the media, is an American media personality who came to international attention when she gave birth to the first surviving octuplets in January 2009.
came to international attention after having twelve embryos implanted, eight of which survived, resulting in eight newborns being added to her existing six-child family. The Medical Board of California sought to have fertility doctor Michael Kamrava, who treated Suleman, stripped of his licence. State officials allege that performing Suleman's procedure is evidence of unreasonable judgment, substandard care, and a lack of concern for the eight children she would conceive and the six she was already struggling to raise. On 1 June 2011 the Medical Board issued a ruling that Kamrava's medical licence be revoked effective 1 July 2011.
Transgender parents
The research and literature on transgender reproduction and family planning today remains extremely limited. There is, however, no evidence to suggest that children of transgender parents are disadvantaged. A study done in France compared the children of transgender fathers to children of cisgender parents and found the childhood development of both groups to be the same and the psycho-emotional health of the children of transgender parents to be good.
A 2020 literature review clearly shows that transgender men and women can experience many obstacles and challenges achieving pregnancy and forming families. These issues stem from the cis-normative structure within United States medical system that leads to transphobic discrimination. Ethical concerns include reproductive rights, reproductive justice, physician autonomy, and transphobia within the health care setting.
Anonymous donors
Some children conceived by IVF using anonymous
donors
A donor in general is a person, organization or government which donates something voluntarily. The term is usually used to represent a form of pure altruism, but is sometimes used when the payment for a service is recognized by all parties as rep ...
report being troubled over not knowing about their donor parent as well any genetic relatives they may have and their family history.
Alana Stewart, who was conceived using donor sperm, began an online forum for donor children called AnonymousUS in 2010. The forum welcomes the viewpoints of anyone involved in the IVF process. Olivia Pratten, a donor-conceived Canadian, sued the province of British Columbia for access to records on her donor father's identity in 2008. "I'm not a treatment, I'm a person, and those records belong to me," Pratten said. In May 2012, a court ruled in Pratten's favour, agreeing that the laws at the time discriminated against donor children and making anonymous sperm and egg donation in British Columbia illegal.
In the U.K., Sweden, Norway, Germany, Italy, New Zealand, and some Australian states, donors are not paid and cannot be anonymous.
In 2000, a website called
Donor Sibling Registry
The Donor Sibling Registry is a website and non-profit US organization serving donor offspring, sperm donors, egg donors and other donor conceived people. It was founded in September 2000 by a mother-and-son team, Wendy Kramer and Ryan Kramer ...
was created to help biological children with a common donor connect with each other.
In 2012, a documentary called ''Anonymous Father's Day'' was released that focuses on donor-conceived children.
Unwanted embryos
During the
selection
Selection may refer to:
Science
* Selection (biology), also called natural selection, selection in evolution
** Sex selection, in genetics
** Mate selection, in mating
** Sexual selection in humans, in human sexuality
** Human mating strategie ...
and transfer phases, many embryos may be discarded in favour of others. This selection may be based on criteria such as genetic disorders or the sex. One of the earliest cases of special gene selection through IVF was the case of the Collins family in the 1990s, who selected the sex of their child. The ethic issues remain unresolved as no consensus exists in science, religion, and philosophy on when a human embryo should be recognised as a person. For those who believe that this is at the moment of conception, IVF becomes a moral question when multiple eggs are fertilised, begin development, and only a few are chosen for uterus transfer.
If IVF were to involve the fertilisation of only a single egg, or at least only the number that will be transferred, then this would not be an issue. However, this has the chance of increasing costs dramatically as only a few eggs can be attempted at a time. As a result, the couple must decide what to do with these extra embryos. Depending on their view of the embryo's humanity or the chance the couple will want to try to have another child, the couple has multiple options for dealing with these extra embryos. Couples can choose to keep them frozen, donate them to other infertile couples, thaw them, or donate them to medical research. Keeping them frozen costs money, donating them does not ensure they will survive, thawing them renders them immediately unviable, and medical research results in their termination. In the realm of medical research, the couple is not necessarily told what the embryos will be used for, and as a result, some can be used in
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
research, a field perceived to have ethical issues.
Religious response
The
Catholic Church
The Catholic Church, also known as the Roman Catholic Church, is the largest Christian church, with 1.3 billion baptized Catholics worldwide . It is among the world's oldest and largest international institutions, and has played a ...
opposes all kinds of
assisted reproductive technology
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
and artificial
contraception
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
, on the grounds that they separate the procreative goal of
marital sex
Marriage, also called matrimony or wedlock, is a culturally and often legally recognized union between people called spouses. It establishes rights and obligations between them, as well as between them and their children, and between t ...
from the goal of uniting married couples.
The Catholic Church permits the use of a small number of reproductive technologies and contraceptive methods such as
natural family planning
Natural family planning (NFP) comprises the family planning methods approved by the Catholic Church and some Protestant denominations for both achieving and postponing or avoiding pregnancy. In accordance with the Church's teachings regarding s ...
, which involves charting ovulation times, and allows other forms of reproductive technologies that allow conception to take place from normative sexual intercourse, such as a fertility lubricant. Pope Benedict XVI had publicly re-emphasised the Catholic Church's opposition to in vitro fertilisation, saying that it replaces love between a husband and wife.
The Catechism of the Catholic Church, in accordance with the Catholic understanding of
natural law
Natural law ( la, ius naturale, ''lex naturalis'') is a system of law based on a close observation of human nature, and based on values intrinsic to human nature that can be deduced and applied independently of positive law (the express enacte ...
, teaches that reproduction has an "inseparable connection" to the sexual union of married couples. In addition, the church opposes IVF because it might result in the disposal of embryos; in Catholicism, an embryo is viewed as an individual with a
soul
In many religious and philosophical traditions, there is a belief that a soul is "the immaterial aspect or essence of a human being".
Etymology
The Modern English noun ''soul'' is derived from Old English ''sāwol, sāwel''. The earliest attes ...
that must be treated as a person.Reconciling religion and infertility By Alina Dain. 30 July 2009 The Catholic Church maintains that it is not objectively evil to be infertile, and advocates adoption as an option for such couples who still wish to have children.
Hindu
Hindus (; ) are people who religiously adhere to Hinduism.Jeffery D. Long (2007), A Vision for Hinduism, IB Tauris, , pages 35–37 Historically, the term has also been used as a geographical, cultural, and later religious identifier for ...
s welcome IVF as a gift for those who are unable to bear children and have declared doctors related to IVF to be conducting punya as there are several characters who were claimed to be born without intercourse, mainly
Kaurav
''Kaurava'' is a Sanskrit term which refers to descendants of Kuru, a legendary king of India who is the ancestor of many of the characters of the epic ''Mahabharata''. Usually, the term is used for the 100 sons of King Dhritarashtra and his wi ...
and five
Pandava
The Pandavas (Sanskrit: पाण्डव, IAST: Pāṇḍava) refers to the five legendary brothers— Yudhishthira, Bhima, Arjuna, Nakula and Sahadeva—who are the central characters of the Hindu epic ''Mahabharata''. They are acknowledg ...
s.
Regarding the response to IVF by
Islam
Islam (; ar, ۘالِإسلَام, , ) is an Abrahamic religions, Abrahamic Monotheism#Islam, monotheistic religion centred primarily around the Quran, a religious text considered by Muslims to be the direct word of God in Islam, God (or ...
, a general consensus from the contemporary Sunni scholars concludes that IVF methods are immoral and prohibited. However, Gad El-Hak Ali Gad El-Hak's ART fatwa includes that:
*IVF of an egg from the wife with the sperm of her husband and the transfer of the fertilised egg back to the uterus of the wife is allowed, provided that the procedure is indicated for a medical reason and is carried out by an expert physician.
*Since marriage is a contract between the wife and husband during the span of their marriage, no third party should intrude into the marital functions of sex and procreation. This means that a third party donor is not acceptable, whether he or she is providing sperm, eggs, embryos, or a uterus. The use of a third party is tantamount to ''zina'', or
adultery
Adultery (from Latin ''adulterium'') is extramarital sex that is considered objectionable on social, religious, moral, or legal grounds. Although the sexual activities that constitute adultery vary, as well as the social, religious, and legal ...
.
Within the
Orthodox Jewish
Orthodox Judaism is the collective term for the traditionalist and theologically conservative branches of contemporary Judaism. Theologically, it is chiefly defined by regarding the Torah, both Written and Oral, as revealed by God to Moses on M ...
community the concept is debated as there is little precedent in traditional Jewish legal textual sources. Regarding laws of sexuality, religious challenges include
masturbation
Masturbation is the sexual stimulation of one's own genitals for sexual arousal or other sexual pleasure, usually to the point of orgasm. The stimulation may involve hands, fingers, everyday objects, sex toys such as vibrators, or combinatio ...
(which may be regarded as "seed wasting"), laws related to sexual activity and menstruation (
niddah
Niddah (or nidah; he, נִדָּה), in traditional Judaism, describes a woman who has experienced a uterine discharge of blood (most commonly during menstruation), or a woman who has menstruated and not yet completed the associated requirem ...
) and the specific laws regarding intercourse. An additional major issue is that of establishing paternity and lineage. For a baby conceived naturally, the father's identity is determined by a legal presumption (
chazakah
In Jewish law, a chazakah (Hebrew חזקה, "presumption") is a legal presumption; it establishes burden of proof. There exist many such presumptions, for example regarding the ownership of property, a person's personal status (e.g. whether the ...
) of legitimacy: ''rov bi'ot achar ha'baal'' – a woman's
sexual relations
Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) t ...
are assumed to be with her husband. Regarding an IVF child, this assumption does not exist and as such Rabbi
Eliezer Waldenberg
Eliezer Yehuda Waldenberg ( he, הרב אליעזר יהודה וולדנברג; December 10, 1915 – November 21, 2006) was a rabbi, posek, and dayan in Jerusalem. He is known as a leading authority on medicine and Jewish law and referred to as ...
(among others) requires an outside supervisor to positively identify the father.
Reform Judaism
Reform Judaism, also known as Liberal Judaism or Progressive Judaism, is a major Jewish denomination that emphasizes the evolving nature of Judaism, the superiority of its ethical aspects to its ceremonial ones, and belief in a continuous searc ...
has generally approved IVF.
Society and culture
Many women of sub-Saharan Africa choose to foster their children to infertile women. IVF enables these infertile women to have their own children, which imposes new ideals to a culture in which fostering children is seen as both natural and culturally important. Many infertile women are able to earn more respect in their society by taking care of the children of other mothers, and this may be lost if they choose to use IVF instead. As IVF is seen as unnatural, it may even hinder their societal position as opposed to making them equal with fertile women. It is also economically advantageous for infertile women to raise foster children as it gives these children greater ability to access resources that are important for their development and also aids the development of their society at large. If IVF becomes more popular without the birth rate decreasing, there could be more large family homes with fewer options to send their newborn children. This could result in an increase of orphaned children and/or a decrease in resources for the children of large families. This would ultimately stifle the children's and the community's growth.
In the US, the
pineapple
The pineapple (''Ananas comosus'') is a tropical plant with an edible fruit; it is the most economically significant plant in the family Bromeliaceae. The pineapple is indigenous to South America, where it has been cultivated for many centuri ...
has emerged as a symbol of IVF users, possibly because some people thought, without scientific evidence, that eating pineapple might slightly increase the success rate for the procedure.
LGBTQ+ community and IVF
Same-sex couples
In larger urban centres, studies have noted that lesbian, gay, bisexual, transgender and queer (LGBTQ+) populations are among the fastest-growing users of fertility care.IVF is increasingly being used to allow lesbian and other LGBT couples to share in the reproductive process through a technique called
reciprocal IVF Partner-assisted reproduction, reception of oocytes from partner (ROPA), reciprocal IVF, shared motherhood, partner IVF or co-IVF is a method of Family planning, family building that is used by couples who both possess female reproductive organs. Th ...
. The eggs of one partner are used to create embryos which the other partner carries through pregnancy. For gay male couples, many elect to use IVF through gestational surrogacy, where one partner's sperm is used to fertilise a donor ovum, and the resulting embryo is transplanted into a surrogate carrier's womb. There are various IVF options available for same-sex couples including, but not limited to, IVF with donor sperm, IVF with a partner’s oocytes, reciprocal IVF, IVF with donor eggs, and IVF with gestational surrogate. IVF with donor sperm can be considered traditional IVF for lesbian couples, but reciprocal IVF or using a partner’s oocytes are other options for lesbian couples trying to conceive to include both partners in the biological process. Using a partner’s oocytes is an option for partners who are unsuccessful in conceiving with their own, and reciprocal IVF involves undergoing reproduction with a donor egg and sperm that is then transferred to a partner who will gestate. Donor IVF involves conceiving with a third party’s eggs. Typically, for gay male couples hoping to use IVF, the common techniques are using IVF with donor eggs and gestational surrogates.
Transgender parents
Many LGBT communities centre their support around cisgender gay, lesbian and bisexual people and neglect to include proper support for transgender people.The same 2020 literature review analyses the social, emotional and physical experiences of pregnant transgender men. A common obstacle faced by pregnant transgender men is the possibility of
gender dysphoria
Gender dysphoria (GD) is the distress a person experiences due to a mismatch between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The diagnostic label gender identity disorder (GID) was used until ...
. Literature shows that transgender men report uncomfortable procedures and interactions during their pregnancies as well as feeling misgendered due to gendered terminology used by healthcare providers. Outside of the healthcare system, pregnant transgender men may experience gender dysphoria due to cultural assumptions that all pregnant people are cisgender women. These people use three common approaches to navigating their pregnancy: passing as a cisgender woman, hiding their pregnancy, or being out and visibly pregnant as a transgender man. Some transgender and gender diverse patients describe their experience in seeking gynaecological and reproductive health care as isolating and discriminatory, as the strictly binary healthcare system often leads to denial of healthcare coverage or unnecessary revelation of their transgender status to their employer.
Many transgender people retain their original sex organs and choose to have children through biological reproduction. Recent advances in assisted reproductive technology and fertility preservation have broadened the options transgender people have to conceive a child using their own gametes or a donor's. Transgender men and women may opt for fertility preservation before any gender affirming surgery, but it is not required for future biological reproduction. It is also recommended that fertility preservation is conducted before any hormone therapy. Additionally, while fertility specialists often suggest that transgender men discontinue their testosterone hormones prior to pregnancy, research on this topic is still inconclusive. However, a 2019 study found that transgender male patients seeking oocyte retrieval via assisted reproductive technology (including IVF) were able to undergo treatment four months after stopping testosterone treatment, on average. All patients experienced menses and normal AMH, FSH and E2 levels and antral follicle counts after coming off testosterone, which allowed for successful oocyte retrieval. Despite assumptions that the long-term androgen treatment negatively impacts fertility, oocyte retrieval, an integral part of the IVF process, does not appear to be affected.
Biological reproductive options available to transgender women include, but are not limited to, IVF and IUI with the trans woman's sperm and a donor or a partner's eggs and uterus. Fertility treatment options for transgender men include, but are not limited to, IUI or IVF using his own eggs with a donor's sperm and/or donor's eggs, his uterus, or a different uterus, whether that is a partner's or a surrogate's.
Emotional involvement with children
Studies have indicated that IVF mothers show greater emotional involvement with their child, and they enjoy motherhood more than mothers by natural conception. Similarly, studies have indicated that IVF fathers express more warmth and emotional involvement than fathers by adoption and natural conception and enjoy fatherhood more. Some IVF parents become overly involved with their children.
Men and IVF
Research has shown that men largely view themselves as "passive contributors" since they have "less physical involvement" in IVF treatment. Despite this, many men feel distressed after seeing the toll of hormonal injections and ongoing physical intervention on their female partner.Throsby, K, Gill, R 2004, '"it's different for men": masculinity and IVF', LSE Research Online, Men and Masculinities, vol. 6, no. 4, pp. 344
Fertility was found to be a significant factor in a man's perception of his masculinity, driving many to keep the treatment a secret. In cases where the men did share that he and his partner were undergoing IVF, they reported to have been teased, mainly by other men, although some viewed this as an affirmation of support and friendship. For others, this led to feeling socially isolated. In comparison with females, males showed less deterioration in mental health in the years following a failed treatment. However, many men did feel guilt, disappointment and inadequacy, stating that they were simply trying to provide an "emotional rock" for their partners.
Cost of IVF
Costs of IVF can be broken down into direct and indirect costs. Direct costs include the medical treatments themselves, including doctor consultations, medications, ultrasound scanning, laboratory tests, the actual IVF procedure, and any associated hospital charges and administrative costs. Indirect costs includes the cost of addressing any complications with treatments, compensation for the gestational surrogate, patients' travel costs, and lost hours of productivity. These costs can be exaggerated by the increasing age of the woman undergoing IVF treatment (particularly those over the age of 40), and the increase costs associated with multiple births. For instance, a pregnancy with twins can cost up to three times that of a singleton pregnancy. While some insurances cover one cycle of IVF, it takes multiple cycles of IVF to have a successful outcome. A study completed in Northern California reveals that the IVF procedure alone that results in a successful outcome costs $61,377, and this can be more costly with the use of a donor egg.
In the US, nineteen states have laws requiring insurance coverage for infertility treatment, and thirteen of those specifically include IVF. These states that mandate IVF coverage are: Arkansas, California, Colorado, Connecticut, Delaware, Hawaii, Illinois, Louisiana, Maryland, Massachusetts, Montana, New Hampshire, New Jersey, New York, Ohio, Rhode Island, Texas, Utah, and West Virginia. These laws differ by state but many require an egg be fertilised with sperm from a spouse and that in order to be covered you must show you cannot become pregnant through penile-vaginal sex. These requirements are not possible for a same-sex couple to meet. No state Medicaid program, however, covers for IVF according to a 2020 report.
Navigating insurance coverage for transgender expectant parents presents a unique challenge. Insurance plans are designed to cater towards a specific population, meaning that some plans can provide adequate coverage for gender-affirming care but fail to provide fertility services for transgender patients. Additionally, insurance coverage is constructed around a person's legally recognised sex and not their anatomy; thus, transgender people may not get coverage for the services they need, including transgender men for fertility services.
Availability and utilisation
High costs keep IVF out of reach for many developing countries, but research by the Genk Institute for Fertility Technology, in Belgium, claim to have found a much lower cost methodology (about 90% reduction) with similar efficacy, which may be suitable for some fertility treatment.
Moreover, the laws of many countries permit IVF for only single individuals, lesbian couples, and persons participating in surrogacy arrangements. Using PGD gives members of these select demographic groups disproportionate access to a means of creating a child possessing characteristics that they consider "ideal," raising issues of equal opportunity for both the parents'/parent's and the child's generation. Many fertile couples now demand equal access to embryonic screening so that their child can be just as healthy as one created through IVF. Mass use of PGD, especially as a means of
population control
Population control is the practice of artificially maintaining the size of any population. It simply refers to the act of limiting the size of an animal population so that it remains manageable, as opposed to the act of protecting a species from ...
or in the presence of legal measures related to population or demographic control, can lead to intentional or
unintentional
''Unintentional'' is a 2021 Nigerian romantic drama film directed by Olufemi Bamigbetan, written by Zeina Otonjo, produced by Obinna Okerekeocha and Bola Atta as Executive Producer and stars Efa Iwara, Omowumi Dada and Beverly Osu
Unintentional ...
demographic effects such as the skewed live-birth sex ratios seen in communist China following implementation of its
one-child policy
The term one-child policy () refers to a population planning initiative in China implemented between 1980 and 2015 to curb the country's population growth by restricting many families to a single child. That initiative was part of a much bro ...
.
The high cost of IVF is also a barrier to access for individuals with disabilities. People with disabilities typically have lower incomes, face higher health care costs, and seek health care services more often than people without disabilities. Adding on the high cost of multiple cycles of IVF, this deters many disabled individuals from pursuing fertility treatment and makes it completely unaccessible for most.
Australia
In Australia, the average age of women undergoing ART treatment is 35.5 years among those using their own eggs (one in four being 40 or older) and 40.5 years among those using
donated eggs
Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
. While IVF is available in Australia, Australians using IVF are unable to choose their baby's gender.
Cameroon
Ernestine Gwet Bell
Ernestine Gwet-Bell (born 1953) is a gynaecologist from Cameroon, who supervised the first successful in vitro fertilisation (IVF) treatment in Cameroon.
Early life
Gwet-Bell was born in 1953 in Sackbayémé, in the department of Sanaga Ma ...
supervised the first Cameroonian child born by IVF in 1998.
Canada
In Canada, one cycle of IVF treatment can cost between $7,750 to $12,250 CAD, and medications alone can cost between $2,500 to over $7,000 CAD. The funding mechanisms that influence accessibility in Canada vary by province and territory, with some provinces providing full, partial or no coverage.
New Brunswick
New Brunswick (french: Nouveau-Brunswick, , locally ) is one of the thirteen provinces and territories of Canada. It is one of the three Maritime provinces and one of the four Atlantic provinces. It is the only province with both English and ...
provides partial funding through their Infertility Special Assistance Fund – a one time grant of up to $5,000. Patients may only claim up to 50% of treatment costs or $5,000 (whichever is less) occurred after April 2014. Eligible patients must be a full-time New Brunswick resident with a vali Medicare card and have an official medical infertility diagnosis by a physician.
In December 2015, the
Ontario
Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central Ca ...
provincial government enacted the Ontario Fertility Program for patients with medical and non-medical infertility, regardless of sexual orientation, gender or family composition. Eligible patients for IVF treatment must be Ontario residents under the age of 43 and have a valid
Ontario Health Insurance Plan
The Ontario Health Insurance Plan ( French: ''Assurance-Santé de l'Ontario''), commonly known in both official languages by the acronym OHIP (pronounced ), is the government- run health insurance plan for the Canadian province of Ontario. OHI ...
card and have not already undergone any IVF cycles. Coverage is extensive, but not universal. Coverage extends to certain blood and urine tests, physician/nurse counselling and consultations, certain ultrasounds, up to two cycle monitorings, embryo thawing, freezing and culture, fertilisation and embryology services, single transfers of all embryos, and one surgical sperm retrieval using certain techniques only if necessary. Drugs and medications are not covered under this Program, along with psychologist or social worker counselling, storage and shipping of eggs, sperm or embryos, and the purchase of donor sperm or eggs.
China
IVF is expensive in China and not generally accessible to unmarried women. In August 2022, China's National Health Authority announced that it will take steps to make assisted reproductive technology more accessible, including by guiding local governments to include such technology in its national medical system.
India
The penetration of the IVF market in India is quite low, with only 2,800 cycles per million infertile people in the reproductive age group (20–44 years), as compared to China, which has 6,500 cycles. The key challenges are lack of awareness, affordability and accessibility. Since 2018, however, India has become a destination for fertility tourism, because of lower costs than in the Western world. In December 2021, the
Lok Sabha
The Lok Sabha, constitutionally the House of the People, is the lower house of India's bicameral Parliament, with the upper house being the Rajya Sabha. Members of the Lok Sabha are elected by an adult universal suffrage and a first-past ...
passed the Assisted Reproductive Technology (Regulation) Bill 2020, to regulate ART services including IVF centres, sperm and egg banks.
Israel
Israel has the highest rate of IVF in the world, with 1657 procedures performed per million people per year. Couples without children can receive funding for IVF for up to two children. The same funding is available for people without children who will raise up to 2 children in a
single parent
A single parent is a person who has a child or children but does not have a spouse or live-in partner to assist in the upbringing or support of the child. Reasons for becoming a single parent include divorce, break-up, abandonment, becoming wid ...
home. IVF is available for people aged 18 to 45. The Israeli Health Ministry says it spends roughly $3450 per procedure.
Sweden
One, two or three IVF treatments are government subsidised for people who are younger than 40 and have no children. The rules for how many treatments are subsidised, and the upper age limit for the people, vary between different
county councils
A county council is the elected administrative body governing an area known as a county. This term has slightly different meanings in different countries.
Ireland
The county councils created under British rule in 1899 continue to exist in Irela ...
. Single people are treated, and embryo adoption is allowed. There are also private clinics that offer the treatment for a fee.
United Kingdom
Availability of IVF in England is determined by
Clinical Commissioning Group
Clinical commissioning groups (CCGs) were NHS organisations set up by the Health and Social Care Act 2012 to organise the delivery of NHS services in each of their local areas in England. On 1 July 2022 they were abolished and replaced by Integra ...
s (CCGs). The
National Institute for Health and Care Excellence
The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas:
* the use of health technologies withi ...
(NICE) recommends up to 3 cycles of treatment for people under 40 years old with minimal success conceiving after 2 years of unprotected sex. Cycles will not be continued for people who are older than 40 years. CCGs in
Essex
Essex () is a county in the East of England. One of the home counties, it borders Suffolk and Cambridgeshire to the north, the North Sea to the east, Hertfordshire to the west, Kent across the estuary of the River Thames to the south, and G ...
,
Bedfordshire
Bedfordshire (; abbreviated Beds) is a ceremonial county in the East of England. The county has been administered by three unitary authorities, Borough of Bedford, Central Bedfordshire and Borough of Luton, since Bedfordshire County Council wa ...
and
Somerset
( en, All The People of Somerset)
, locator_map =
, coordinates =
, region = South West England
, established_date = Ancient
, established_by =
, preceded_by =
, origin =
, lord_lieutenant_office =Lord Lieutenant of Somerset
, lord_ ...
have reduced funding to one cycle, or none, and it is expected that reductions will become more widespread. Funding may be available in "exceptional circumstances" – for example if a male partner has a transmittable infection or one partner is affected by cancer treatment. According to the campaign group Fertility Fairness "at the end of 2014 every CCG in England was funding at least one cycle of IVF". Prices paid by the
NHS
The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
in England varied between under £3,000 to more than £6,000 in 2014/5. In February 2013, the cost of implementing the NICE guidelines for IVF along with other treatments for infertility was projected to be £236,000 per year per 100,000 members of the population.
IVF increasingly appears on
NHS treatments blacklist
The NHS treatments blacklist is an informal name for a list of medicines and procedures which will not be funded by public money except in exceptional cases. These include but are not limited to procedures which the National Institute for Health ...
s. In August 2017 five of the 208 CCGs had stopped funding IVF completely and others were considering doing so. By October 2017 only 25 CCGs were delivering the three recommended NHS IVF cycles to eligible people under 40. Policies could fall foul of discrimination laws if they treat same sex couples differently from heterosexual ones. In July 2019
Jackie Doyle-Price
Jacqueline Doyle-Price (born 5 August 1969) is a British Conservative Party politician and former civil servant. She was first elected as the Member of Parliament (MP) for Thurrock in the 2010 general election.
In September 2022, she was app ...
said that women were registering with surgeries further away from their own home in order to get around CCG rationing policies.
The
Human Fertilisation and Embryology Authority
The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the United ...
said in September 2018 that parents who are limited to one cycle of IVF, or have to fund it themselves, are more likely choose to implant multiple embryos in the hope it increases the chances of pregnancy. This significantly increases the chance of multiple births and the associated poor outcomes, which would increase NHS costs. The president of the
Royal College of Obstetricians and Gynaecologists
The Royal College of Obstetricians and Gynaecologists (RCOG) is a professional association based in London, United Kingdom. Its members, including people with and without medical degrees, work in the field of obstetrics and gynaecology, that is ...
said that funding 3 cycles was "the most important factor in maintaining low rates of multiple pregnancies and reduce(s) associated complications".
United States
In the United States, overall availability of IVF in 2005 was 2.5 IVF physicians per 100,000 population, and utilisation was 236 IVF cycles per 100,000. 126 procedures are performed per million people per year. Utilisation highly increases with availability and IVF insurance coverage, and to a significant extent also with percentage of single persons and median income. In the US, an average cycle, from egg retrieval to embryo implantation, costs $12,400, and insurance companies that do cover treatment, even partially, usually cap the number of cycles they pay for. As of 2015, more than 1 million babies had been born utilising IVF technologies.
The cost of IVF rather reflects the costliness of the underlying healthcare system than the regulatory or funding environment, and ranges, on average for a standard IVF cycle and in 2006 United States dollars, between $12,500 in the United States to $4,000 in Japan. In Ireland, IVF costs around €4,000, with fertility drugs, if required, costing up to €3,000. The cost per live birth is highest in the United States ($41,000) and United Kingdom ($40,000) and lowest in Scandinavia and Japan (both around $24,500).
Many fertility clinics in the United States limit the upper age at which people are eligible for IVF to 50 or 55 years.Appel, J.M. (15 July 2009 Motherhood: Is It Ever Too Late? New York Times These cut-offs make it difficult for people older than fifty-five to utilise the procedure.
Alternatives
Alternatives to IVF are mainly:
*
Artificial insemination
Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatme ...
, including
intracervical insemination
Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment ...
and
intrauterine insemination
Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment ...
of semen. It requires that a woman ovulates, but is a relatively simple procedure, and can be used in the home for self-insemination without medical practitioner assistance.Seattle Sperm Bank /ref> The beneficiaries of artificial insemination are people who desire to give birth to their own child who may be single, people who are in a
lesbian
A lesbian is a Homosexuality, homosexual woman.Zimmerman, p. 453. The word is also used for women in relation to their sexual identity or sexual behavior, regardless of sexual orientation, or as an adjective to characterize or associate n ...
relationship or females who are in a
heterosexual
Heterosexuality is romantic attraction, sexual attraction or sexual behavior between people of the opposite sex or gender. As a sexual orientation, heterosexuality is "an enduring pattern of emotional, romantic, and/or sexual attractions" to ...
relationship but with a male partner who is
infertile
Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
or who has a physical impairment which prevents full intercourse from taking place.
*
Ovulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles Ovulation Induction Retrieved on Mars 7, 2010 to reverse anovulation or oligoovulation.
Scop ...
(in the sense of medical treatment aiming for the development of one or two ovulatory follicles) is an alternative for people with
anovulation
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulat ...
or
oligoovulation
Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
, since it is less expensive and more easy to control. It generally involves
antiestrogen
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhi ...
s such as
clomifene citrate
Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. Use results in a greater chance of twins. It is taken by mouth once a day, with a course ...
or
letrozole
Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer.
It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...
, and is followed by
natural
Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are p ...
or artificial insemination.
*
Surrogacy
Surrogacy is an arrangement, often supported by a legal agreement, whereby a woman agrees to delivery/labour for another person or people, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnan ...
, the process in which a surrogate agrees to bear a child for another person or persons, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnancy is medically impossible, when
pregnancy risks
Complications of pregnancy are health problems that are related to pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are termed puerperal di ...
are too dangerous for the intended gestational carrier, or when a single man or a male couple wish to have a child. "
All in My Family
''All in My Family'' is a 2019 American short film, short documentary film directed by Hao Wu (director), Hao Wu. The film follows a traditional heterosexual family where the son is a gay Chinese man who has chosen to have children via surrogates ...
" is a documentary that immerses viewers into the life of a gay couple pursuing surrogacy as a means to form their own family.
*
Adoption
Adoption is a process whereby a person assumes the parenting of another, usually a child, from that person's biological or legal parent or parents. Legal adoptions permanently transfer all rights and responsibilities, along with filiation, from ...
whereby a person assumes the
parenting
Parenting or child rearing promotes and supports the physical, emotional, social, spiritual and intellectual development of a child from infancy to adulthood. Parenting refers to the intricacies of raising a child and not exclusively for a ...
of another, usually a child, from that person's biological or legal parent or parents.
Legal status
Government agencies in China passed bans on the use of IVF in 2003 by unmarried people or by couples with certain infectious diseases.
In India, the use of IVF as a means of sex selection (
preimplantation genetic diagnosis
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
) is banned under the
Pre-Conception and Pre-Natal Diagnostic Techniques Act, 1994
Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act, 1994 is an Act of Parliament, Act of the Parliament of India enacted to stop female foeticides and arrest the declining sex ratio in India. The act banned prenatal sex determinati ...
.
Sunni Muslim nations generally allow IVF between married couples when conducted with their own respective sperm and eggs, but not with donor eggs from other couples. But Iran, which is Shi'a Muslim, has a more complex scheme. Iran bans sperm donation but allows donation of both fertilised and unfertilised eggs. Fertilised eggs are donated from married couples to other married couples, while unfertilised eggs are donated in the context of mut'ah or temporary marriage to the father.
By 2012
Costa Rica
Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...
was the only country in the world with a complete ban on IVF technology, it having been ruled unconstitutional by the nation's Supreme Court because it "violated life." Costa Rica had been the only country in the western hemisphere that forbade IVF. A law project sent reluctantly by the government of President
Laura Chinchilla
Laura Chinchilla Miranda (; born 28 March 1959) is a Costa Rican politician who was President of Costa Rica from 2010 to 2014. She was one of Óscar Arias Sánchez's two Vice-Presidents and his administration's Minister of Justice. She was the ...
was rejected by parliament. President Chinchilla has not publicly stated her position on the question of IVF. However, given the massive influence of the Catholic Church in her government any change in the status quo seems very unlikely. In spite of Costa Rican government and strong religious opposition, the IVF ban has been struck down by the Inter-American Court of Human Rights in a decision of 20 December 2012. The court said that a long-standing Costa Rican guarantee of protection for every human embryo violated the reproductive freedom of infertile couples because it prohibited them from using IVF, which often involves the disposal of embryos not implanted in a woman's uterus. On 10 September 2015, President Luis Guillermo Solís signed a decree legalising in-vitro fertilisation. The decree was added to the country's official gazette on 11 September. Opponents of the practice have since filed a lawsuit before the country's Constitutional Court.
All major restrictions on single but infertile people using IVF were lifted in Australia in 2002 after a final appeal to the Australian High Court was rejected on procedural grounds in the Leesa Meldrum case. A Victorian federal court had ruled in 2000 that the existing ban on all single women and lesbians using IVF constituted sex discrimination. Victoria's government announced changes to its IVF law in 2007 eliminating remaining restrictions on fertile single women and lesbians, leaving South Australia as the only state maintaining them.
Federal regulations in the United States include screening requirements and restrictions on donations, but generally do not affect sexually intimate partners. However, doctors may be required to ''provide'' treatments due to nondiscrimination laws, as for example in California. The US state of
Tennessee
Tennessee ( , ), officially the State of Tennessee, is a landlocked state in the Southeastern region of the United States. Tennessee is the 36th-largest by area and the 15th-most populous of the 50 states. It is bordered by Kentucky to th ...
proposed a bill in 2009 that would have defined donor IVF as adoption. During the same session another bill proposed barring adoption from any unmarried and cohabitating couple, and activist groups stated that passing the first bill would effectively stop unmarried women from using IVF. Neither of these bills passed.
Few American courts have addressed the issue of the "property" status of a frozen embryo. This issue might arise in the context of a divorce case, in which a court would need to determine which spouse would be able to decide the disposition of the embryos. It could also arise in the context of a dispute between a sperm donor and egg donor, even if they were unmarried. In 2015, an Illinois court held that such disputes could be decided by reference to any contract between the parents-to-be. In the absence of a contract, the court would weigh the relative interests of the parties.
Disability and IVF
Individuals with disabilities are just as entitled to equitable access to fertility treatment such as IVF as individuals without disabilities. However, most of the time this access is not granted. In fact, people with disabilities who wish to have children are equally or more likely than the non-disabled population to experience infertility, yet disabled individuals are much less likely to have access to fertility treatment such as IVF. There are many extraneous factors that hinder disabled individuals access to IVF, such as assumptions about decision making capacity, sexual interests and abilities, heritability of a disability, and beliefs about parenting ability. Assumptions like these may be the reason that people with disabilities unjustly receive less access to medically indicated reproductive care than other people of similar age and sex. These same misconceptions about people with disabilities that once led health care providers to sterilise thousands of women with disabilities now lead them to provide or deny reproductive care on the basis of stereotypes concerning people with disabilities and their sexuality.
Not only do misconceptions about disabled individuals parenting ability, sexuality, and health restrict and hinder access to fertility treatment such as IVF, structural barriers such as providers uneducated in disability healthcare and inaccessible clinics severely hinder disabled individuals access to receiving IVF. Non handicap accessible buildings, medical equipment, exam tables, etc. are all barriers that make accessing IVF almost impossible for individuals with disabilities. A woman named Nia shares her story on how accessing IVF as a disabled blind person was extremely difficult, if not almost impossible. She tells us how transportation to the clinic was inaccessible for a disabled individual, the medication given for IVF was extremely hard to self administer, and her providers were uninformed on how to make the IVF process disability accessible. Stories like Nia's show us how fertility treatment such as IVF are inequitably inaccessible for disabled individuals and why they need to be disability friendly in order to protect the right to parent for individuals with disabilities.
There are obvious indications that access to IVF and similar fertility treatments are much less accessible for individuals with disabilities. Even though the ASRM states that "children thrive within a wide range of parenting approaches or homes" as well as that it is "inaccurate to assume that being disabled means having no sexual or reproductive interests or being sexually inactive, celibate, or asexual, assumptions about disabled individuals sexuality and parenting ability paired with uniformed providers and lack of accessible clinics and medical equipment hinder access to fertility treatment such as IVF for disabled individuals. Steps need to be taken to make the field of fertility accessible to all, and protect the right to start a family despite ability level.
See also
*
Semen cryopreservation
Semen cryopreservation (commonly called sperm banking or sperm freezing) is a procedure to preserve sperm cells. Semen can be used successfully indefinitely after cryopreservation. It can be used for sperm donation where the recipient wants the tr ...
* ''
Evans v United Kingdom
''Evans v. the United Kingdom'' was a key case at the European Court of Human Rights. The case outcome could have had a major impact on fertility law, not only within the United Kingdom but also the other Council of Europe countries.
Professor J ...
'', a key case at the
European Court of Human Rights
The European Court of Human Rights (ECHR or ECtHR), also known as the Strasbourg Court, is an international court of the Council of Europe which interprets the European Convention on Human Rights. The court hears applications alleging that a ...
*
Sex selection
Sex selection is the attempt to control the sex of the offspring to achieve a desired sex. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at childbirth. It has been marketed under the title family ...
*
Stem cell controversy
The stem cell controversy is the consideration of the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For e ...
*
Reciprocal IVF Partner-assisted reproduction, reception of oocytes from partner (ROPA), reciprocal IVF, shared motherhood, partner IVF or co-IVF is a method of Family planning, family building that is used by couples who both possess female reproductive organs. Th ...
*
Test Tube Babies (film)
''Test Tube Babies'', also known as ''Blessed Are They'' (American reissue title), ''Sins of Love'' (American reissue title) and ''The Pill'' (America reissue title, recut version), is a 1948 exploitation film directed by W. Merle Connell and pro ...
Human Fertilisation and Embryology Authority
The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the United ...
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...