Recurrent Miscarriage: Causes, Evaluation, and Treatment
from Medscape General Medicine™
Diethylstilbesterol Exposure in Utero
From 1945 to 1971, diethylstilbesterol (DES), a synthetic estrogen, was prescribed for women with threatened or recurrent spontaneous abortion. The use of this agent in pregnant women was then banned in the US. The first evidence of the drug's adverse effects, which occurred a generation removed from the time of administration, was the report by Herbst and Scully in 1970, indicating an increased incidence of vaginal adenosis and clear cell adenocarcinoma of the vagina. There is often relative absence of the vaginal fornices and a "cockscomb" or "hooded" deformity of the anterior cervix. The female offspring of DES-treated women may also have a diminution in the size and capacity of the uterus. The classical appearance of the constricted endometrial cavity on hysterosalpingogram is a "T" configuration. The severity of the abnormality is variable, depending on the dose and duration of administration of the drug during embryogenesis. Women who underwent DES exposure in utero experience an increased likelihood of ectopic pregnancy as well as first- and second-trimester spontaneous fetal losses and preterm labor.
In some cases, the likelihood of second-trimester pregnancy loss resulting from cervical incompetence may be diminished with cervical cerclage. Vigilant assessment of cervical length with transvaginal sonography allows the clinician to identify patients who may benefit from cerclage. When treating patients with DES-induced abnormalities, the surgeon should be liberal in the performance of cerclage. Other than cervical cerclage, surgical intervention rarely improves anatomic abnormality of the DES-affected uterus.
Painless cervical dilatation during the second trimester, followed by bulging or rupture of the membranes and delivery of an immature fetus, typically suggests cervical incompetence. When cervical dilatation is advanced but membranes remain intact, it may be possible to perform cerclage. In this situation, a tocolytic agent may be necessary; the intervention is technically difficult to perform and frequently fails to salvage the pregnancy.
Often effective, therapeutic leverage may be applied during a subsequent pregnancy. Plans should be made to perform the cerclage by the tenth week of gestation or soon thereafter. Various techniques have been used to close the cervix at the level of the internal os. The most common surgical techniques for cerclage are minor variations of those described by Shirodkar and McDonald. The stitch should be removed by week 37 or upon active labor, to avoid amputation of the cervix. When vaginal fornices are absent and a secure transvaginal cerclage is impossible, a transabdominal cerclage should be considered.
Congenital Müllerian Duct Malformations
The anatomic variations of the müllerian duct malformation are legion. The classic abnormality associated with recurrent second-trimester fetal loss is the septate uterus. The vertical septum extends a variable length from the fundus toward the cervix. The septum may be thick or thin, entirely fibrous or vascular, and partially covered by a layer of endometrium. In addition, the "compartments" into which the uterine cavity is divided by the septum may not be symmetrical. These anatomic variants, as well as the site of embryo implantation, dictate whether the septum might cause first- or second-trimester spontaneous abortion or preterm labor, or whether it will not present a problem.
Symptoms other than fetal loss seldom lead to the detection of müllerian duct malformation. Hysterosalpingogram and sonography usually establish the diagnosis, although on occasion there is difficulty in distinguishing the septate from the bicornuate uterus. Historically, clinicians required that a patient have 2 or 3 miscarriages before offering surgical intervention. In that era, laparotomy was required, and the septum was excised according to the techniques described by Jones or by Tompkins. Both of these surgical procedures necessitated bivalving the uterus. Customary postoperative recommendations included deferring conception for at least several months to ensure complete healing of the uterine incision. It was also suggested that the subsequent delivery be performed by cesarean section.
Today, the management of this malformation is simple incision of the septum with a scissors at hysteroscopy. Routinely, the hysteroscopy is accompanied by laparoscopy to distinguish definitively septate from bicornuate uteri and to ensure that the dissection of the septum is not overzealous. The bicornuate uterus would rarely require surgical intervention to improve obstetric outcome.
In addition to the aforementioned duct malformations, unicornuate and hypoplastic uteri are common. Magnetic resonance imaging (MRI) is most useful in delineating the malformation when the abnormality cannot be precisely discerned by sonogram and hysterosalpingogram.
Many women with fibroids (if not the majority) have normal fertility and pregnancies that are without complication. Spontaneous abortion related to a leiomoyoma is the consequence of either the size or strategic location of the lesion. Submucous intracavitary fibroids are the most likely to interfere with successful progression of an early pregnancy. Large intramural lesions that compress the endometrial cavity, thereby altering the blood supply to the implantation site, may also cause early termination of pregnancy. Even very large subserous fibroids are unlikely to cause early disruption of pregnancy in the absence of an unusual event (acute degeneration resulting in an increase in myometrial contractions). Submucous lesions are almost always associated with a history of menorrhagia.
The hysterosalpingogram has been a traditional test to assess compromise of the endometrial cavity by fibroids. Sonography and, in selected instances, hysterosonography are helpful in determining the relevance of fibroids to pregnancy wastage. In exceptional instances, pelvic MRI may be required to define the pathology. Pretreatment with a gonadotropin-releasing hormone (GnRH) agonist is frequently used to reduce the size of the fibroid before surgical intervention; such treatment also may diminish intraoperative blood loss. Large intramural leiomyomas necessitate myomectomy through laparotomy or laparoscopy, depending on the size/location of the tumor and the operative skills/experience of the surgeon. Submucous fibroids are usually best managed with a resectoscope at hysteroscopy.
Intrauterine synechiae are an infrequent cause of spontaneous abortion. Diagnosis is made by hysterosalpingogram or hysterosonography, and lysis of the intracavitary adhesions may be performed under direct vision during hysteroscopy.
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