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Asherman's syndrome (AS) is an acquired uterine condition that occurs when scar tissue (
adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can be ...
s) forms inside the uterus and/or the cervix. It is characterized by variable scarring inside the uterine cavity, where in many cases the front and back walls of the uterus stick to one another. AS can be the cause of menstrual disturbances, infertility, and placental abnormalities. Although the first case of intrauterine adhesion was published in 1894 by Heinrich Fritsch, it was only after 54 years that a full description of Asherman syndrome was carried out by Joseph Asherman. A number of other terms have been used to describe the condition and related conditions including: uterine/cervical atresia, traumatic uterine atrophy, sclerotic endometrium, and endometrial sclerosis. There is not any one cause of AS. Risk factors can include
myomectomy Myomectomy, sometimes also called fibroidectomy, refers to the surgical removal of uterine leiomyomas, also known as fibroids. In contrast to a hysterectomy, the uterus remains preserved and the woman retains her reproductive potential. Indicati ...
,
cesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or mo ...
, infections, age, genital tuberculosis, and obesity. Genetic predisposition to AS is being investigated. There are also studies that show that a severe pelvic infection, independent of surgery may cause AS. AS can develop even if the woman has not had any uterine surgeries, trauma, or pregnancies. While rare in North America and European countries, genital tuberculosis is a cause of Asherman's in other countries such as India.


History

The condition was first described in 1894 by
Heinrich Fritsch Heinrich Fritsch (5 December 1844 – 12 May 1915) was a German gynecologist and obstetrician who was a native of Halle an der Saale. He studied medicine at the Universities of Tübingen, Würzburg and Halle. He became a member of Suevia ...
(Fritsch, 1894) and further characterized by the
Israeli Israeli may refer to: * Something of, from, or related to the State of Israel * Israelis, citizens or permanent residents of the State of Israel * Modern Hebrew, a language * ''Israeli'' (newspaper), published from 2006 to 2008 * Guni Israeli ...
gynecologist Joseph Asherman (1889–1968) in 1948. It is also known as Fritsch syndrome, or Fritsch-Asherman syndrome.


Signs and symptoms

It is often characterized by a decrease in flow and duration of bleeding ( absence of menstrual bleeding, little menstrual bleeding, or infrequent menstrual bleeding) and
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 ...
.
Menstrual 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 ...
anomalies are often but not always correlated with severity: adhesions restricted to only the
cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
or lower
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 ...
may block
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
. Pain during
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
and
ovulation 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 ...
is sometimes experienced and can be attributed to blockages. It has been reported that 88% of AS cases occur after a D&C is performed on a recently
pregnant Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
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 ...
, following a missed or incomplete
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 ...
,
birth Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
, or during an elective termination (
abortion Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...
) to remove
retained products of conception Retained placenta is a condition in which all or part of the placenta or membranes remain in the uterus during the third stage of labour. Retained placenta can be broadly divided into: * failed separation of the placenta from the uterine lining * p ...
.


Causes

The cavity of 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 ...
is lined by the
endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
. This lining is composed of two layers, the functional layer (adjacent to the uterine cavity) which is shed during
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
and an underlying basal layer (adjacent to the myometrium), which is necessary for regenerating the functional layer. Trauma to the basal layer, typically after a
dilation and curettage Dilation (or dilatation) and curettage (D&C) refers to the dilation (widening/opening) of the cervix and surgical removal of part of the lining of the uterus and/or contents of the uterus by scraping and scooping (curettage). It is a gynecologic ...
(D&C) performed after a
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 delivery, or
abortion Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...
, can lead to the development of intrauterine scars resulting in
adhesions Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connects tissues not normally connected. Pathophysiology Adhesions form as a natural ...
that can obliterate the cavity to varying degrees. In the extreme, the whole cavity can be scarred and occluded. Even with relatively few scars, the
endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
may fail to respond to
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
. Asherman's syndrome affects women of all races and ages equally, suggesting no underlying genetic predisposition for its development. AS can result from other pelvic surgeries including
cesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or mo ...
s, removal of fibroid tumours (
myomectomy Myomectomy, sometimes also called fibroidectomy, refers to the surgical removal of uterine leiomyomas, also known as fibroids. In contrast to a hysterectomy, the uterus remains preserved and the woman retains her reproductive potential. Indicati ...
) and from other causes such as
IUDs An intrauterine device (IUD), also known as intrauterine contraceptive device (IUCD or ICD) or coil, is a small, often T-shaped birth control device that is inserted into the uterus to prevent pregnancy. IUDs are one form of long-acting revers ...
, pelvic
irradiation Irradiation is the process by which an object is exposed to radiation. The exposure can originate from various sources, including natural sources. Most frequently the term refers to ionizing radiation, and to a level of radiation that will serve ...
,
schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody s ...
and genital tuberculosis. Chronic endometritis from genital tuberculosis is a significant cause of severe intrauterine adhesions (IUA) in the developing world, often resulting in total obliteration of the uterine cavity which is difficult to treat. An artificial form of AS can be surgically induced by
endometrial ablation Endometrial ablation is a surgical procedure that is used to remove (ablate) or destroy the endometrial lining of the uterus in people who have heavy menstrual bleeding. Endometrial ablation is not recommended for people who wish to have childre ...
in women with excessive uterine bleeding, in lieu of
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
.


Diagnosis

The history of a
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 ...
event followed by a D&C leading to secondary amenorrhea or hypomenorrhea is typical. Hysteroscopy is the gold standard for diagnosis. Imaging by
sonohysterography 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 ...
or
hysterosalpingography Hysterosalpingography (HSG), also known as uterosalpingography, is a radiologic procedure to investigate the shape of the uterine cavity and the shape and patency of the Fallopian tubes. It is a special x-ray using dye to look at the womb (uter ...
will reveal the extent of the scar formation. Ultrasound is not a reliable method of diagnosing Asherman's Syndrome. Hormone studies show normal levels consistent with reproductive function.


Classification

Various classification systems were developed to describe Asherman's syndrome (citations to be added), some taking into account the amount of functioning residual endometrium, menstrual pattern, obstetric history and other factors which are thought to play a role in determining the prognoses. With the advent of techniques which allow visualization of the uterus, classification systems were developed to take into account the location and severity of adhesions inside the uterus. This is useful as mild cases with adhesions restricted to the cervix may present with amenorrhea and infertility, showing that symptoms alone do not necessarily reflect severity. Other patients may have no adhesions but amenorrhea and infertility due to a sclerotic atrophic endometrium. The latter form has the worst prognosis.


Prevention

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, ...
concluded that there were no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to surgical management (e.g. D&C), medical management or conservative management (that is,
watchful waiting Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expec ...
). There is an association between surgical intervention in the uterus and the development of intrauterine adhesions, and between intrauterine adhesions and pregnancy outcomes, but there is still no clear evidence of any method of prevention of adverse pregnancy outcomes. In theory, the recently pregnant uterus is particularly soft under the influence of hormones and hence, easily injured. D&C (including dilation and curettage, dilation and evacuation/suction curettage and manual vacuum aspiration) is a blind, invasive procedure, making it difficult to avoid endometrial trauma. Medical alternatives to D&C for evacuation of retained placenta/products of conception exist including
misoprostol Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. Misoprostol is taken by mouth wh ...
and
mifepristone Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of p ...
. Studies show this less invasive and cheaper method to be an efficacious, safe and an acceptable alternative to surgical management for most women. It was suggested as early as in 1993 that the incidence of IUA might be lower following medical evacuation (e.g. Misoprostol) of the uterus, thus avoiding any intrauterine instrumentation. So far, one study supports this proposal, showing that women who were treated for missed miscarriage with misoprostol did not develop IUA, while 7.7% of those undergoing D&C did. The advantage of misoprostol is that it can be used for evacuation not only following miscarriage, but also following birth for retained placenta or hemorrhaging. Alternatively, D&C could be performed under ultrasound guidance rather than as a blind procedure. This would enable the surgeon to end scraping the lining when all retained tissue has been removed, avoiding injury. Early monitoring during pregnancy to identify miscarriage can prevent the development of, or as the case may be, the recurrence of AS, as the longer the period after fetal death following D&C, the more likely adhesions may be to occur. Therefore, immediate evacuation following fetal death may prevent IUA.The use of hysteroscopic surgery instead of D&C to remove retained products of conception or placenta is another alternative that could theoretically improve future pregnancy outcomes, although it could be less effective if tissue is abundant. Also, hysteroscopy is not a widely or routinely used technique and requires expertise. There is no data to indicate that suction D&C is less likely than sharp curette to result in Asherman's. A recent article describes three cases of women who developed intrauterine adhesions following manual vacuum aspiration. Intrauterine adhesions also form after hysteroscopic surgery such as
myomectomy Myomectomy, sometimes also called fibroidectomy, refers to the surgical removal of uterine leiomyomas, also known as fibroids. In contrast to a hysterectomy, the uterus remains preserved and the woman retains her reproductive potential. Indicati ...
, polypectomy or septum removal. Mechanical barriers such as Womed Leaf or hyaluronic acid gels can be used to prevent formation of IUA after such adhesiogenic procedures or after D&C.


Treatment

Fertility may sometimes be restored by removal of adhesions, depending on the severity of the initial trauma and other individual patient factors. Operative
hysteroscopy Hysteroscopy is the inspection of the uterine cavity by endoscopy with access through the cervix. It allows for the diagnosis of intrauterine pathology and serves as a method for surgical intervention (operative hysteroscopy). Hysteroscope A hyst ...
is used for visual inspection of the uterine cavity during adhesion dissection (adhesiolysis). However, hysteroscopy is yet to become a routine gynaecological procedure and only 15% of US gynecologists perform office hysteroscopy. Adhesion dissection can be technically difficult and must be performed with care in order to not create new scars and further exacerbate the condition. In more severe cases, adjunctive measures such as laparoscopy are used in conjunction with hysteroscopy as a protective measure against uterine perforation. Microscissors are usually used to cut adhesions. Electrocauterization is not recommended. As IUA frequently reform after surgery, techniques have been developed to prevent recurrence of adhesions. Methods to prevent adhesion reformation include the use of mechanical barriers (Foley catheter, saline-filled balloon uterine stents, gel barriers (Seprafilm, Spraygel, autocrosslinked hyaluronic acid gel Hyalobarrier) and mechanical barrier film (Womed Leaf) to maintain opposing walls apart during healing, thereby preventing the reformation of adhesions. Antibiotic prophylaxis is necessary in the presence of mechanical barriers to reduce the risk of possible infections. A common pharmacological method for preventing reformation of adhesions is sequential hormonal therapy with
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
followed by a progestin to stimulate endometrial growth and prevent opposing walls from fusing together. However, there have been no
randomized controlled trials 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 te ...
(RCTs) comparing post-surgical adhesion reformation with and without hormonal treatment and the ideal dosing regimen or length of estrogen therapy is not known. A recent meta analysis compared different post surgical prevention barrier strategies and concluded that there was no single clearly superior treatment. Furthermore, diagnostic severity and outcomes are assessed according to different criteria (e.g. menstrual pattern, adhesion reformation rate, conception rate, live birth rate). Clearly, more comparable studies are needed in which reproductive outcome can be analysed systematically. Follow-up tests (HSG, hysteroscopy or SHG) are necessary to ensure that adhesions have not reformed. Further surgery may be necessary to restore a normal uterine cavity. According to a recent study among 61 patients, the overall rate of adhesion recurrence was 27.9% and in severe cases this was 41.9%. Another study found that postoperative adhesions reoccur in close to 50% of severe AS and in 21.6% of moderate cases. Mild IUA, unlike moderate to severe synechiae, do not appear to reform.


Prognosis

The extent of adhesion formation is critical. Mild to moderate adhesions can usually be treated with success. Extensive obliteration of the uterine cavity or fallopian tube openings ( ostia) and deep endometrial or myometrial trauma may require several surgical interventions and/or hormone therapy or even be uncorrectable. If the uterine cavity is adhesion free but the ostia remain obliterated,
IVF 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) fr ...
remains an option. If the uterus has been irreparably damaged,
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 ...
or
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 ...
may be the only options. Depending on the degree of severity, AS may result in
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 ...
, repeated
miscarriages 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 ...
, pain from trapped blood, and future obstetric complications If left untreated, the obstruction of
menstrual 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 ...
flow resulting from
adhesions Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connects tissues not normally connected. Pathophysiology Adhesions form as a natural ...
can lead to
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
in some cases. Patients who carry a
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 ...
even after treatment of IUA may have an increased risk of having abnormal placentation including
placenta accreta Placenta accreta occurs when all or part of the placenta attaches abnormally to the ''myometrium'' (the muscular layer of the uterine wall). Three grades of abnormal placental attachment are defined according to the depth of attachment and invasio ...
where the placenta invades 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 ...
more deeply, leading to complications in placental separation after delivery. Premature delivery, second-trimester pregnancy loss, and uterine rupture are other reported complications. They may also develop incompetent cervix where the cervix can no longer support the growing weight of the fetus, the pressure causes the placenta to rupture and the mother goes into premature labour. Cerclage is a surgical stitch which helps support the cervix if needed. Pregnancy and live birth rate has been reported to be related to the initial severity of the adhesions with 93, 78, and 57% pregnancies achieved after treatment of mild, moderate and severe adhesions, respectively and resulting in 81, 66, and 32% live birth rates, respectively. The overall pregnancy rate after adhesiolysis was 60% and the live birth rate was 38.9% according to one study. Age is another factor contributing to fertility outcomes after treatment of AS. For women under 35 years of age treated for severe adhesions, pregnancy rates were 66.6% compared to 23.5% in women older than 35.


Epidemiology

AS has a reported incidence of 25% of D&Cs performed 1–4 weeks post-partum, up to 30.9% of D&Cs performed for missed miscarriages and 6.4% of D&Cs performed for incomplete miscarriages. In another study, 40% of patients who underwent repeated D&C for retained products of conception after missed miscarriage or retained placenta developed AS. In the case of missed miscarriages, the time period between fetal demise and curettage may increase the likelihood of adhesion formation due to fibroblastic activity of the remaining tissue. The risk of AS also increases with the number of procedures: one study estimated the risk to be 16% after one D&C and 32% after three or more D&Cs. However, a single curettage often underlies the condition. In an attempts to estimate the
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
of AS in the general population, it was found in 1.5% of women undergoing
hysterosalpingography Hysterosalpingography (HSG), also known as uterosalpingography, is a radiologic procedure to investigate the shape of the uterine cavity and the shape and patency of the Fallopian tubes. It is a special x-ray using dye to look at the womb (uter ...
HSG, and between 5 and 39% of women with recurrent miscarriage. After miscarriage, a
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, ...
estimated the prevalence of AS to be approximately 20% (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 ...
: 13% to 28%).


References


External links

*
Sophie Blake Sophie Blake (born 9 November 1972), is an English television presenter and former model. Career Blake studied drama, and then travelled working in bars and restaurants for a few years. She did some modelling, and put a home-made show-reel tog ...
talks about being diagnosed with Asherman's syndrome. * * * (awareness, education, prevention) * {{DEFAULTSORT:Asherman's Syndrome Fertility Noninflammatory disorders of female genital tract Health issues in pregnancy Gynaecologic disorders Pregnancy with abortive outcome Disorders related to length of gestation and fetal growth Syndromes affecting female reproductive system