Induction of final maturation of
oocyte
An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
s is a procedure that is usually performed as part of
controlled ovarian hyperstimulation 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 oocyte retrieval (egg collect ...
to render the oocytes fully developed and thereby resulting in optimal
pregnancy chance 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. It is basically a replacement for the
luteinizing hormone (LH) surge whose effects include final maturation in natural
menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
s.
The main medications used for induction of final maturation are
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) and
GnRH agonist. In fresh (rather than
frozen
Frozen may refer to:
* the result of freezing
* a paralysis response in extreme cases of fear
Films
* ''Frozen'' (1997 film), a film by Wang Xiaoshuai
* ''Frozen'' (2005 film), a film by Juliet McKoen
* ''Frozen'' (2007 film), a film by Sh ...
)
autologous cycles of
''in vitro'' fertilization, final oocyte maturation triggering with GnRH agonist instead of hCG decreases the 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 ...
but decreases
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 ...
. In cycles followed by
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 ...
, use of GnRH agonists instead of hCG decreases the risk of ovarian hyperstimulation syndrome with no evidence of a difference in live birth rate.
Usage with ovulation
Induction of final maturation also initiates the mechanisms that eventually result in
ovulation, and thereby makes the oocytes destined to undergo ovulation unless artificial
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 ...
is performed first. Therefore, induction of final maturation is also called triggering oocyte release from the ovary, and the administration of
pharmaceutical drug
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
s to induce final maturation is colloquially called giving a "trigger shot", even if the plan is to perform artificial oocyte retrieval before ovulation.
Administration of a drug to trigger oocyte release without oocyte retrieval results in a predictable time of ovulation, with the interval from drug administration to ovulation depending on the type of drug. This avails for
sexual intercourse
Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetrat ...
or
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 ...
(IUI) to conveniently be scheduled at ovulation, the most likely time to achieve pregnancy.
[IVF.com > Ovulation Induction]
Retrieved on Mars 7, 2010
In
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 ...
, using
clomifene for intended conception by sexual intercourse, however, triggering oocyte release has been shown to decrease pregnancy chances compared to frequent monitoring with
LH surge
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) ...
tests.
Therefore, in such cases, triggering oocyte release is best reserved for women who require IUI and in whom LH monitoring proves difficult or unreliable.
[ It may also be used when LH monitoring hasn't shown an LH surge by cycle day 18 (where cycle day 1 is the first day of the preceding menstruation) and there is an ]ovarian follicle
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 300,000 follicles, each with th ...
of over 20 mm in size.[Clomiphene Citrate, Clomid]
. By Robert B. McWilliams. The Center for Reproduction and Women's Health Care, Houston, Texas. Retrieved May 2014
Usage with artificial oocyte retrieval
In ''in vitro'' fertilization (IVF), induction of final maturation avails for egg 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 ...
when the eggs are fully mature.
In IVF, final maturation induction is preceded by controlled ovarian hyperstimulation 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 oocyte retrieval (egg collect ...
. It is suggested that there should be a size of ovarian follicle
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 300,000 follicles, each with th ...
s of at least 15 mm, and serum estradiol level of 0.49 nmol/L before commencing final maturation induction. There are better prospects at a follicle size of 18 mm and serum estradiol level of 0.91 nmol/L.
Medications
Medications used for final maturation and/or release of oocytes include:
* 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 or hCG) in a low dose, which may be injected after completed ovarian stimulation. Final maturation with hCG is also termed hCG priming.[ ] Ovulation will occur between 38 and 40 hours after a single HCG injection.HCG Injection After Ovulation Induction With Clomiphene Citrate
at Medscape. By Peter Kovacs. Posted: 04/23/2004 It is also used in
''in vitro'' fertilization, where it makes the follicles perform their final maturation. A
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 ...
is then performed at a time usually between 34 and 36 hours after hCG injection, that is, shortly before when the follicles would rupture. A retrieval at 36 hours after final maturation induction appears to result in optimal embryo quality and pregnancy outcomes.
[ ] 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 ...
.
*
Recombinant luteinizing hormone (rLH), recombinant HCG (rHCG) and
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
-derived hCG (uHCG) are equally effective in achieving final follicular maturation in IVF with regards to pregnancy rates and risk of ovarian hyperstimulation syndrome.
Therefore, urine-derived hCG (uHCG) is regarded as the best choice for final oocyte maturation triggering in IVF due to availability and cost.
*
GnRH agonist, which necessitates using 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 for
suppression of ovulation during ovarian hyperstimulation, because using GnRH agonist for that purpose as well inactivates the axis for which it is intended to work for final maturation induction.
HCG versus GnRH agonist
Final maturation induction using GnRH agonist results in a substantial decrease in the 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). 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 ...
estimated that using GnRH agonist instead of hCG in IVF decreases the risk of mild, moderate or severe OHSS 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 approximately 0.15. The review estimated that, for a woman with a 5% risk of mild, moderate or severe OHSS with the use of HCG, the risk of OHSS with the use of a GnRH agonist would be between 0 and 2%.
However, using GnRH agonist has a lower
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 ...
than when using hCG in
autologous oocyte transfers (rather than ones using
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 ...
). A Cochrane review of autologous oocyte transfers estimated that GnRH agonist, compared to hCG, gives 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 0.47. It estimated that, for a woman with a 31% chance of achieving live birth with the use of hCG, the chance of a live birth with the use of an GnRH agonist would be between 12% and 24%.
Likewise, using GnRH agonist instead of hCG was associated with a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) than was seen with HCG (odds ratio 0.70) and a higher rate of early (less than 12 weeks)
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 ...
(odds ratio 1.74). However, a higher pregnancy rate when using hCG is only found in those receiving
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 ...
without
luteinizing hormone activity (such as
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 ...
or
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 ...
).
Final maturation induction using a GnRH agonist is recommended in women with cancer undergoing
fertility preservation, because ovarian hyperstimulation syndrome is associated with an increased risk of arterial thrombotic events such as
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
and peripheral
arterial embolism
Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmona ...
, and this risk can add to an already increased risk caused by the cancer.
Using hCG versus GnRH agonist has no effect on the risk of
multiple pregnancy.
Also, no difference has been found between the regimens regarding
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 ongoing
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 ...
when the controlled ovarian hyperstimulation was followed by
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 ...
.
References
{{reflist
Fertility
Female genital procedures
Fertility medicine
Obstetrics
Human pregnancy
Reproduction