The American Society for Reproductive Medicine’s classification system for müllerian anomalies was the standard until the revision in 2021 by ASRM, which updated and expanded the classification presenting nine classes and imaging criteria: müllerian agenesis, cervical agenesis, unicornuate, uterus didelphys, bicornuate, septate, longitudinal vaginal septum, transverse vaginal septum, and complex anomalies. This month’s article addresses müllerian anomalies from embryology to treatment options.
The early embryo has the capability of developing a wolffian (internal male) or müllerian (internal female) system. Unless anti-müllerian hormone (formerly müllerian-inhibiting substance) is produced, the embryo develops a female reproductive system beginning with two lateral uterine anlagen that fuse in the midline and canalize. Müllerian anomalies occur because of accidents during fusion and canalization (see Table).
Dr. Mark P. Trolice
The incidence of müllerian anomalies is difficult to discern, given the potential for a normal reproductive outcome precluding an evaluation and based on the population studied. Müllerian anomalies are found in approximately 4.3% of fertile women, 3.5%-8% of infertile patients, 12.3%-13% of those with recurrent pregnancy losses, and 24.5% of patients with miscarriage and infertility. Of the müllerian anomalies, the most common is septate (35%), followed by bicornuate (26%), arcuate (18%), unicornuate (10%), didelphys (8%), and agenesis (3%) (Hum Reprod Update. 2001;7[2]:161; Hum Reprod Update. 2011;17[6]:761-71).
In 20%-30% of patients with müllerian anomalies, particularly in women with a unicornuate uterus, renal anomalies exist that are typically ipsilateral to the absent or rudimentary contralateral uterine horn (J Pediatr Adolesc Gynecol. 2021;34[2]:154-60). As there is no definitive evidence to suggest an association between a septate uterus and renal anomalies, the renal system evaluation can be deferred in this population (Fertil Steril. 2021 Nov;116[5]:1238-52).
Diagnosis
2-D ultrasound can be a screen for müllerian anomalies and genitourinary anatomic variants. The diagnostic accuracy of 3-D ultrasound with müllerian anomalies is reported to be 97.6% with sensitivity and specificity of 98.3% and 99.4%, respectively (Hum. Reprod. 2016;31[1]:2-7). As a result, office 3-D has essentially replaced MRI in the diagnosis of müllerian anomalies (Ultrasound Obstet Gynecol. 2015 Nov;46[5]:616-22), with one exception because of the avoidance of a transvaginal probe in the non–sexually active adult and younger adolescent/child. MRI is reserved for diagnosing complex müllerian anomalies or if there is a diagnostic challenge.
Criteria to diagnose müllerian anomalies by radiology begins with the “reference line,” i.e., a line joining both tubal ostia (interostial line). A septate uterus is diagnosed if the distance from the interostial line to the cephalad endometrium is more than 1 cm, otherwise it is considered normal or arcuate based on its appearance. An arcuate uterus has not been associated with impaired reproduction and can be viewed as a normal variant. Alternatively, a bicornuate uterus is diagnosed when the external fundal indentation is more than 1 cm (Fertil Steril. 2021 Nov;116[5]:1238-52).
Clinical course
Women with müllerian anomalies may experience pelvic pain and prolonged and/or abnormal bleeding at the time of menarche. While the ability to conceive may not be impaired from müllerian anomalies with the possible exception of the septate uterus, the pregnancy course can be affected, i.e., recurrent pregnancy loss, preterm birth, perinatal mortality, and malpresentation in labor (Reprod Biomed Online. 2014;29[6]:665). In women with septate, bicornuate, and uterine didelphys, fetal growth restriction appears to be increased. Spontaneous abortion rates of 32% and preterm birth rates of 28% have been reported in patients with uterus didelphys (Obstet Gynecol. 1990;75[6]:906).
Special consideration of the unicornuate is given because of the potential for a rudimentary horn that may communicate with the main uterine cavity and/or have functional endometrium which places the woman at risk of an ectopic pregnancy in the smaller horn. Patients with a unicornuate uterus are at higher risk for preterm labor and breech presentation. An obstructed (noncommunicating) functional rudimentary horn is a risk for endometriosis with cyclic pain because of outflow tract obstruction and an ectopic pregnancy prompting consideration for hemihysterectomy based on symptoms.
The septate uterus – old dogma revisited
The incidence of uterine septa is approximately 1-15 per 1,000. As the most common müllerian anomaly, the septate uterus has traditionally been associated with an increased risk for spontaneous abortion (21%-44%) and preterm birth (12%-33%). The live birth rate ranges from 50% to 72% (Hum Reprod Update. 2001;7[2]:161-74). A uterine septum is believed to develop as a result of failure of resorption of the tissue connecting the two paramesonephric (müllerian) ducts prior to the 20th embryonic week.
Incising the uterine septum (metroplasty) dates back to 1884 when Ruge described a blind transcervical metroplasty in a woman with two previous miscarriages who, postoperatively, delivered a healthy baby. In the early 1900s, Tompkins reported an abdominal metroplasty (Fertil Stertil. 2021;115:1140-2). The decision to proceed with metroplasty is based on only established observational studies (Fertil Steril. 2016;106:530-40). Until recently, the majority of studies suggested that metroplasty is associated with decreased spontaneous abortion rates and improved obstetrical outcomes. A retrospective case series of 361 patients with a septate uterus who had primary infertility of >2 years’ duration, a history of 1-2 spontaneous abortions, or recurrent pregnancy loss suggested a significant improvement in the live birth rate and reduction in miscarriage (Arch Gynecol Obstet. 2003;268:289-92). A meta-analysis found that the overall pregnancy rate after septum incision was 67.8% and the live-birth rate was 53.5% (J Minim Invas Gynecol. 2013;20:22-42).
Recently, two multinational studies question the prevailing dogma (Fertil Steril. 2021 Sep;116[3]:693-4). Both studies could not demonstrate any increase in live birth rate, reduction in preterm birth, or in pregnancy loss after metroplasty. A significant limitation was the lack of a uniform consensus on the definition of the septate uterus and allowing the discretion of the physician to diagnosis a septum (Hum Reprod. 2020;35:1578-88; Hum Reprod. 2021;36:1260-7).
Hysteroscopic metroplasty is not without complications. Uterine rupture during pregnancy or delivery, while rare, may be linked to significant entry into the myometrium and/or overzealous cauterization and perforation, which emphasizes the importance of appropriate techniques.
Conclusion
A diagnosis of müllerian anomalies justifies a comprehensive consultation with the patient given the risk of pregnancy complications. Management of the septate uterus has become controversial. In a patient with infertility, prior pregnancy loss, or poor obstetrical outcome, it is reasonable to consider metroplasty; otherwise, expectant management is an option.
Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at obnews@mdedge.com.