How AS causes infertility or miscarriages

Asherman’s syndrome (AS) can lead infertility in a number of ways. No two cases are identical and it can manifest as infertility according to how and which parts of the reproductive anatomy is affected. AS is characterized by intrauterine adhesions (IUA) and/or fibrosis (non-functional scar tissue).

Infertility may be caused by adhesions occluding the tubal ostia, uterine cavity, or the cervix, thereby interfering with the migration of sperm or implantation of the embryo (1). The presence of defective endometrium in the fundus and ostia which are partially obliterated by the adhesions may also predispose women to tubal and cervical pregnancies (2,3). Partial obstruction of tubes can lead to pregnancy complications such as ectopic pregnancy because the fertilized egg may be physically impeded from migrating to the uterus for implantation. If ostial obstruction is so extensive that it cannot be corrected through hysteroscopic adhesiolysis, in vitro fertilization is the only possibility for a biological offspring (providing that the rest of the uterus is functional and adhesion free). Cervical pregnancy (another form of ectopic pregnancy) may occur if the embryo implants in the cervix. Adhesions involving the cervix may result in the cervix being closed (outlet obstruction). This obviously prevents the sperm from encountering the egg. It has also been noted that in women with outlet obstruction due to adhesions blocking the lower uterus or cervix, endometrial measures are thinner than in women where adhesions are limited to the upper uterus (4). It is thought that the underlying cause of this is a feedback loop to prevent haematometra from occurring. Haematometra is the formation of a large clot of blood from trapped menstrual debris and it very rarely occurs in the former subgroup of women.

Another possible way Asherman’s syndrome can result in infertility is by causing endometriosis. Some authors have noted that women with extensive adhesions either in the uterus or cervix, blocking menstrual flow, later develop endometriosis (5). This was discovered because laparoscopic (keyhole) surgery is sometimes carried out at the same time as hysteroscopy when performing adhesiolysis of IUA. Laparoscopy helps to prevent uterine perforation in severe cases where it may be difficult to judge the limits of the uterine cavity. Endometriosis is the growth of endometrial lining outside of the uterus. It can occur anywhere in the body, though most commonly occurs in the abdomen. Although the cause(s) of endometriosis remain unknown, one of the theories put forth by John A. Sampson is known as the theory of retrograde menstruation. It speculates that a back flow of blood and debris through the fallopian tubes and into the abdomen enables its implantation to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. (As an aside to those who practice yoga, this is why inverted positions such as headstands are avoided during menstruation). Endometriosis itself can lead to infertility by causing pelvic adhesions (Note: not to be confused with intrauterine adhesions which occur INSIDE the uterus). Pelvic adhesions (or extrauterine adhesions) can twist and distort the fallopian tubes and prevent fertilization or implantation.

Many women who have had Asherman’s syndrome develop a thin endometrium even after surgical correction and hormonal therapy to stimulate endometrial regeneration. An optimal thickness of the endometrium (>8mm) is considered to be one of the prerequisites for successful implantation of the embryo. Thin endometrium can be caused by either too much of the endometrium having been removed during D&C (or other uterine surgery) or cervical obstruction (as described above). A thin endometrium may be unresponsive to hormones (6) and may lead to infertility in the form of implantation failure or early miscarriages known as ‘chemical pregnancies’ due to a lack of blood supply and poor placental perfusion. Thin endometrium can also occur in women who have had D&Cs, even if they did not develop Asherman’s syndrome. In fact, a recent study found that the endometrium of women is thinner for about 6 months after a D&C (7). A recent study suggests that treatment with tocopherol (ie. vitamin E) and pentoxifylline may help to thicken the endometrium (8), improving implantation. Of course IUA must be removed before pregnancy can be attempted.

The exact mechanisms by which IUA predispose to miscarriages are unknown, however, it is suspected that constrictions of the uterine cavity by adhesions, lack of adequate functional endometrium to support implantation and defective vascularisation of the residual endometrial tissue due to fibrosis may account for repeated pregnancy loss (9). If an embryo implants in an adhesion or a fibrotic region, it will not grow successfully because it will not have an adequate blood supply, essential for providing the growing embryo with oxygen and nutrients. This can lead to miscarriage. Interestingly, this is analogous to the situation where women with Mullerian malformations such as septate uterus often undergo miscarriage when the embryo implants in the septum (10). If IUAs obstruct the openings of one or both of the fallopian tubes (known as ostia) this prevents the sperm from fertilizing the egg (which normally happens in the fallopian tubes after ovulation).

There is another potential cause of second trimester miscarriage which has been often reported in women with a past history of Asherman’s syndrome: cervical incompetence, also known and cervical insufficiency, however, I will write about this under a future blog topic, post-Asherman’s syndrome obstetric complications, since these miscarriages are not due to adhesions or fibrosis per se but to previous dilations of the cervix during surgeries.


As a consequence of the above, many women who have untreated Asherman’s syndrome are either unable to conceive, or suffer from repeated miscarriages. However, depending on the location, extent and severity of IUA/fibrosis, patients may conceive and carry a pregnancy without treatment. This is not recommended and is usually a chance finding on ultrasound when an adhesion or synechia is detected. There have been isolated case reports of successful and uncomplicated pregnancies in the presence of IUA (11). In the best case scenario, the adhesions are minimal and thin, stretching with the pregnancy such that it does not impinge on the growth of the fetus or uterus. However, women are strongly advised to use contraception to avoid pregnancy until surgical correction of adhesions to avoid pregnancy complications. In women who conceive without removal of adhesions, the reproductive outcome is usually poor: in one well known study, it was reported that of the 46% of patients with untreated IUA who conceived, 40% of the pregnancies ended in spontaneous miscarriage, 12% of which were ectopic. Of the viable pregnancies, 23% delivered prematurely and 13% had placenta accreta with only 53% delivering viable infants (12). Obviously, the more severe the classification of AS, the more likely complications are to occur if a pregnancy occurs. On the other hand, pregnancy itself is probably less likely to occur in more severe cases. Note that these complications may also occur in women after treatment of Asherman’s syndrome, however not as frequently. This will be covered in a future blog.

The moral of the story is: get treated by a trusted Asherman’s specialist if you have Asherman’s syndrome and make sure the uterine cavity is clear (via a follow up hysteroscopy or HSG) and that adhesions have not recurred before trying to conceive. Even better, avoid getting Asherman’s syndrome by using alternatives to D&C.


References


1.Yu, D, Wong, YM, Cheong, Y, Xia, E, and Li, TC. Asherman syndrome--one century later. Fertil Steril 2008;89(4):759-79.

2. Dicker, D, Feldberg, D, Samuel, N, and Goldman, JA. Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome. J Reprod Med 1985;30(1):25-7.

3. Forssman, L. Posttraumatic intrauterine synechiae and pregnancy. Obstet Gynecol 1965;26(5):710-3.

4. Lo ST, Ramsay P, Pierson R, Manconi F, Munro MG, Fraser IS. Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions.Hum Reprod. 2008 ;23(2):306-9. Link

5. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. Link

6. Shufaro, Y, Simon, A, Laufer, N, and Fatum, M. Thin unresponsive endometrium--a possible complication of surgical curettage compromising ART outcome. J Assist Reprod Genet 2008;25(8):421-5.

7. Moon KS, Richter KS, Levy MJ, Widra EA. Does dilation and curettage versus expectant management for spontaneous abortion in patients undergoing in vitro fertilization affect subsequent endometrial development? Fertil Steril. 2009;92(5):1776-9. PMID 19560759

8. Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases. Hum Fertil (Camb). 2009;12(4):198-203. Link

9. Polishuk, WZ and Sadovsky, E. A syndrome of recurrent intrauterine adhesions. Am J Obstet Gynecol 1975;123(2):151-8.

10. Golan, A, Schneider, D, Avrech, O, Raziel, A, Bukovsky, I, and Caspi, E.
Hysteroscopic findings after missed abortion. Fertil Steril 1992;58(3):508-10.

11. Klatsky PC, Tran ND, Strachowski L. A pregnancy complicated by endometrial scarring. Fertil Steril. 2009;91(6):2707-8.

12. Schenker, JG and Margalioth, EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril 1982;37(5):593-610.