Four principal deformities arise from defective müllerian duct embryological steps: (1) agenesis of both ducts, either focally or along the entire duct length; (2) unilateral maturation of one müllerian duct with incomplete or absent development of the opposite side; (3) absent or faulty midline fusion of the ducts; or (4) defective canalization. Various classifications have been proposed, and Table 3-3 shows the one from the American Fertility Society (1988). It separates anomalies into groups with similar clinical characteristics, prognosis for pregnancy, and treatment. It also includes one for abnormalities associated with fetal exposure to diethylstilbestrol (DES). Several other classification systems have been crafted, but this one is the most widely used (Acién, 2011; Di Spiezio Sardo, 2015; Oppelt, 2005).
TABLE 3-3Classification of Müllerian Anomalies ||Download (.pdf) TABLE 3-3 Classification of Müllerian Anomalies
|I. ||Segmental müllerian hypoplasia or agenesis |
|II. ||Unicornuate uterus |
Communicating rudimentary horn
No endometrial cavity
No rudimentary horn
|III. ||Uterine didelphys |
|IV. ||Bicornuate uterus |
Complete—division to internal os
|V. ||Septate uterus |
Complete—septum to internal os
|VI. ||Arcuate |
|VII. ||Diethylstilbestrol related |
Müllerian anomalies may be suspected by symptoms or physical findings such as vaginal septa, blind-ending vagina, or duplicated cervix. Amenorrhea may be an initial complaint for those with agenesis of a müllerian component. In those with outlet obstruction, pelvic pain from occult blood that accumulates and distends the vagina, uterus, or fallopian tubes may arise from functioning endometrium. Endometriosis and its associated dysmenorrhea, dyspareunia, and chronic pain are also frequent with outlet obstruction.
Class I segmental defects are caused by müllerian hypoplasia or agenesis as shown in Figure 3-5. These developmental defects can affect the vagina, cervix, uterus, or fallopian tubes and may be isolated or may coexist with other müllerian defects.
Classification of müllerian anomalies. DES = diethylstilbestrol. (Modified with permission from American Fertility Society: The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian anomalies and intrauterine adhesions, Fertil Steril 1988 Jun;49(6):944–55.)
Of all vaginal anomalies, vaginal agenesis is the most profound and may be isolated or associated with other müllerian anomalies. One example is the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, in which upper vaginal agenesis is typically associated with uterine hypoplasia or agenesis. Less often, this syndrome also displays abnormalities of the renal, skeletal, and auditory systems. This triad is known by the acronym MURCS, which reflects müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia (Rall, 2015).
The obstetrical significance of vaginal anomalies depends greatly on the degree of obstruction. Complete vaginal agenesis, unless corrected operatively, precludes pregnancy by vaginal intercourse. With MRKH syndrome, a functional vagina can be created, but uterine agenesis proscribes childbearing. In these women, however, ova can be retrieved for in vitro fertilization (IVF) in a surrogate mother (Friedler, 2016). Uterine transplantation is currently experimental but holds future promise for these women (Johannesson, 2016).
Of other vaginal anomalies, congenital septa may form longitudinally or transversely, and each can arise from a fusion or resorption defect. Longitudinal septa divide the vagina into right and left portions. They may be complete and extend the entire vaginal length. Partial septa usually form high in the vagina but may develop at lower levels. Septa are typically associated with other müllerian anomalies (Haddad, 1997). During labor, a complete longitudinal vaginal septum usually does not cause dystocia because the vaginal side through which the fetus descends dilates satisfactorily. An incomplete or partially obstructed longitudinal septum, however, may interfere with descent. Occasionally, a woman with a distal longitudinal septum presents in labor. During second-stage labor, this septum usually becomes attenuated by pressure from the fetal head. After ensuring adequate analgesia, the inferior attachment of the septum is isolated, clamped, transected, and ligated. Following placenta delivery, the superior attachment can be transected while carefully avoiding urethral injury.
A transverse septum poses an obstruction of variable thickness. It may develop at any depth within the vagina, but most are in the lower third (Williams, 2014). These may or may not be perforate, and thus obstruction or infertility is variably present. In labor, perforate strictures may be mistaken for the upper limit of the vaginal vault, and the septal opening is misidentified as an undilated cervical os (Kumar, 2014). If encountered during labor, and after the external os has dilated completely, the head impinges on the septum and causes it to bulge downward. If the septum does not yield, slight stretching pressure on its opening usually leads to further dilatation, but occasionally cruciate incisions are required to permit delivery (Blanton, 2003). If there is a thick transverse septum, however, cesarean delivery may be necessary.
Developmental abnormalities of the cervix include partial or complete agenesis, duplication, and longitudinal septa. Uncorrected complete agenesis is incompatible with pregnancy, and in vitro fertilization with gestational surrogacy is an option. Surgical correction by uterovaginal anastomosis has resulted in successful pregnancy (Kriplani, 2012). Significant complications accompany this corrective surgery, and the need for clear preoperative anatomy delineation has been emphasized by Rock (2010) and Roberts (2011) and their colleagues. For this reason, they recommend hysterectomy for complete cervical agenesis and reserve reconstruction attempts for carefully selected patients with cervical dysgenesis.
From a large variety, a few of the more common congenital uterine malformations are shown in Table 3-3. An accurate population prevalence of these is difficult to assess because the best diagnostic techniques are invasive. That said, the prevalence found with imaging ranges from 0.4 to 10 percent, and rates in women with recurrent miscarriage are significantly higher (Byrne, 2000; Dreisler, 2014; Saravelos, 2008). In a general population, the most common finding is arcuate uterus, followed in descending order by septate, bicornuate, didelphic, and unicornuate classes (Chan, 2011b).
Müllerian anomalies may be discovered during pelvic examination, cesarean delivery, tubal sterilization, or infertility evaluation. Depending on clinical presentation, diagnostic tools may include sonography, hysterosalpingography, magnetic-resonance imaging, laparoscopy, and hysteroscopy. Each has limitations, and these may be used in combination to completely define anatomy. In women undergoing fertility evaluation, hysterosalpingography (HSG) is commonly selected for uterine cavity and tubal patency assessment. It is contraindicated during pregnancy. HSG poorly defines the external uterine contour and can delineate only patent cavities. Regarding patency, remember that some unicornuate rudimentary horns lack a cavity. Also, outlet obstructions will preclude dye filling.
In most clinical settings, two-dimensional transvaginal sonography (2-D TVS) is initially performed. For this indication, the pooled accuracy for TVS is 90 to 92 percent (Pellerito, 1992). Saline infusion sonography (SIS) improves delineation of the endometrium and internal uterine morphology, but only with a patent endometrial cavity. It also is contraindicated in pregnancy. Three-dimensional (3-D) sonography is more accurate than 2-D sonography because it provides uterine images from virtually any angle. Thus, coronal images can be constructed as shown in Figure 3-6, and these are essential in evaluating both internal and external uterine contours (Grimbizis, 2016). Both 2-D and 3-D sonography are suitable for use in pregnancy.
Three-dimensional transvaginal sonographic images. A. Bicornuate uterus with an 8-week gestation. The external fundal contour (red dotted line) dips centrally below the intercornual line, and the endometrial cavities communicate. B. Septate uterus with a 5-week gestation. The external fundal contour is normal and convex (yellow dotted line), and the long septum (asterisk) extends caudad in the midline. C. Arcuate uterus with an 8-week gestation. The external fundal contour is normal and convex (red dotted line), but the fundal endometrial cavity is slightly indented (arrow).
Several studies have reported very good concordance between 3-D TVS and MR imaging of müllerian anomalies (Deutch, 2008; Graupera, 2015). MR imaging is often preferred for complex anatomy, especially cases for which corrective surgery is planned. MR imaging provides clear delineation of both the internal and external uterine anatomy and has a reported accuracy of up to 100 percent for müllerian anomaly evaluation (Bermejo, 2010; Pellerito, 1992). In addition, complex anomalies and commonly associated secondary diagnoses such as renal or skeletal anomalies can be concurrently evaluated. Precautions with MR imaging in pregnancy are discussed in Chapter 46 (Safety).
In some women undergoing an infertility evaluation, hysteroscopy and laparoscopy may be selected to assess for müllerian anomalies; screen for endometriosis, which is often coexistent; and exclude other tubal or uterine cavity pathologies (Puscheck, 2008; Saravelos, 2008). In pregnancy, these approaches are rarely used to diagnose müllerian anomalies, and hysteroscopy is contraindicated.
Unicornuate Uterus (Class II)
With this abnormality, the underdeveloped or rudimentary horn may be absent. If present, it may or may not communicate with the dominant horn and may or may not contain an endometrium-lined cavity (see Fig. 3-5). General population estimates cite an incidence of 1 in 4000 women (Reichman, 2009). This anomaly may be detected during fertility evaluation by HSG. But as noted, noncommunicating or noncavitary rudimentary horns may not fill with dye. If this anomaly is suspected, 3-D sonography increases diagnostic accuracy, but again MR imaging may be preferred. Importantly, 40 percent of affected women will have renal anomalies (Fedele, 1996).
This müllerian anomaly carries significant obstetrical risks, including first- and second-trimester miscarriage, malpresentation, fetal-growth restriction, fetal demise, prematurely ruptured membranes, and preterm delivery (Chan, 2011a; Hua, 2011; Reichman, 2009). Abnormal uterine blood flow, cervical incompetence, and diminished cavity size and muscle mass of the hemiuterus are postulated to underlie these risks (Donderwinkel, 1992).
Rudimentary horns also increase the risk for an ectopic pregnancy within the remnant, which may be disastrous. This risk includes noncommunicating cavitary rudiments, for which transperitoneal sperm migration permits ovum fertilization and pregnancy (Nahum, 2004). In a report of 70 such pregnancies, Rolen and associates (1966) found that the rudimentary uterine horn ruptured prior to 20 weeks in most. Nahum (2002) reviewed the literature from 1900 to 1999 and identified 588 rudimentary horn pregnancies. Half had uterine rupture, and 80 percent did so before the third trimester. Of the total 588, the neonatal survival rate was only 6 percent.
Imaging allows an earlier diagnosis of rudimentary horn pregnancy so that it can be treated either medically with methotrexate or surgically before rupture (Dove, 2017; Edelman, 2003; Khati, 2012; Worley, 2008). Although not emphasized in Figure 3-5, the attachment site between the rudimentary horn at times can be broad and vascular.
If diagnosed in a nonpregnant woman, most recommend prophylactic excision of a horn that has a cavity (Fedele, 2005; Rackow, 2007). Data regarding subsequent pregnancy after excision are scarce. In one series of eight women, all had a preterm cesarean delivery (Pados, 2014).
Uterine Didelphys (Class III)
This müllerian anomaly arises from a complete lack of fusion that results in two entirely separate hemiuteri, cervices, and usually two vaginas (see Fig. 3-5). It is common among marsupials, for example, the American possum—Didelphys virginiana. Most women have a double vagina or a longitudinal vaginal septum. Uterine didelphys may be isolated. Or, it may compose a triad with an obstructed hemivagina and with ipsilateral renal agenesis (OHVIRA), also known as Herlyn- Werner-Wunderlich syndrome (Tong, 2013).
These anomalies are suspected on pelvic examination by identification of a longitudinal vaginal septum and two cervices. During HSG for fertility evaluation, contrast shows two separate endocervical canals. These open into separate noncommunicating fusiform endometrial cavities that each ends with a solitary fallopian tube. In women without fertility issues, 2- or 3-D TVS is a logical initial imaging tool, and separate divergent uterine horns with a large intervening fundal cleft are seen. Endometrial cavities are uniformly separate. MR imaging may be valuable in cases without classic findings.
Adverse obstetrical outcomes associated with uterine didelphys are similar but less frequent than those seen with unicornuate uterus. Increased risks include miscarriage, preterm birth, and malpresentation (Chan, 2011a; Grimbizis, 2001; Hua, 2011).
Metroplasty for either uterine didelphys or bicornuate uterus involves resection of intervening myometrium and fundal recombination (Alborzi, 2015). These rarely performed surgeries are chosen for highly selected patients with otherwise unexplained miscarriages. Moreover, no evidence-based data confirm the efficacy of such surgical repair.
Bicornuate Uterus (Class IV)
This fusion anomaly results in two hemiuteri. As shown in Figure 3-5, the central myometrium runs either partially or completely to the cervix. A complete bicornuate uterus may extend to the internal cervical os and have a single cervix (bicornuate unicollis) or reach the external os (bicornuate bicollis). As with uterine didelphys, a coexistent longitudinal vaginal septum is not uncommon.
Radiological discrimination of a bicornuate uterus from a septate uterus can be challenging. This distinction, however, is important because septate uterus can be treated with hysteroscopic septal resection. HSG or 2-D TVS may initially suggest an anomaly, but further distinction is provided by 3-D TVS or MR imaging (see Fig. 3-6). With these, an intercornual angle greater than 105 degrees typifies a bicornuate uterus, whereas one less than 75 degrees indicates a septate uterus. Fundal contour also assists, and a straight line drawn between the imaged tubal ostia serves as the defining threshold. Referent to this, an intrafundal downward cleft measuring ≥1 cm or more is indicative of bicornuate uterus. A septate uterus shows a cleft depth <1 cm, or it may have a normal fundal contour.
Bicornuate uterus carries increased risks for adverse obstetrical outcomes that include miscarriage, preterm birth, and malpresentation. As discussed in the prior section, rare surgical correction by metroplasty is reserved for highly selected patients.
With this anomaly, a resorption defect leads to a persistent complete or partial longitudinal uterine septum (see Fig. 3-5). Less often, a complete vaginocervicouterine septum is found (Ludwin, 2013). Many septate uteri are identified during evaluation of infertility or recurrent pregnancy loss. Although an abnormality may be identified with HSG or 2-D TVS, typically 3-D TVS or MR imaging is required to differentiate this from a bicornuate uterus (see Fig. 3-6).
Septate anomalies are associated with diminished fertility and increased risks for adverse pregnancy outcomes that include miscarriage, preterm delivery, and malpresentation (Chan, 2011a; Ghi, 2012). Hysteroscopic septal resection has been shown to improve pregnancy rates and outcomes (Mollo, 2009; Pabuçcu, 2004). From their metaanalysis, Valle and colleagues (2013) reported a 63-percent pregnancy rate and 50-percent live birth rate following resection.
Arcuate Uterus (Class VI)
This malformation is a mild deviation from the normally developed uterus. Although some studies report no increased adverse associated outcomes, others have found excessive second-trimester losses, preterm labor, and malpresentation (Chan, 2011a; Mucowski, 2010; Woelfer, 2001).
Some women with uterine anomalies and repetitive pregnancy losses may benefit from transvaginal or transabdominal cervical cerclage (Golan, 1992; Groom, 2004). Others with partial cervical atresia or hypoplasia may also benefit (Hampton, 1990; Ludmir, 1991). Candidacy for cerclage is determined by the same criteria used for women without such defects, which is discussed in Chapter 18 (Management).
Diethylstilbestrol Reproductive Tract Abnormalities (Class VII)
During the 1960s, a synthetic nonsteroidal estrogen—diethylstilbestrol (DES)—was used to treat pregnant women for threatened abortion, preterm labor, preeclampsia, and diabetes. The treatment was remarkably ineffective. Later, it was also discovered that women exposed as fetuses had increased risks of developing several specific reproductive-tract abnormalities. These included vaginal clear cell adenocarcinoma, cervical intraepithelial neoplasia, small-cell cervical carcinoma, and vaginal adenosis. Affected women had identifiable structural variations in the cervix and vagina that include transverse septa, circumferential ridges, and cervical collars. Uteri potentially had smaller cavities, shortened upper uterine segments, or T-shaped and other irregular cavities (see Fig. 3-5) (Kaufman, 1984).
These women suffer impaired conception rates and higher rates of miscarriage, ectopic pregnancy, and preterm delivery, especially in those with structural abnormalities (Kaufman, 2000; Palmer, 2001). Now, more than 50 years after DES use was proscribed, most affected women are past childbearing age, but higher rates of earlier menopause, cervical intraepithelial neoplasia, and breast cancer are reported in exposed women (Hatch, 2006; Hoover, 2011; Troisi, 2016).
Fallopian Tube Abnormalities
The fallopian tubes develop from the unpaired distal ends of the müllerian ducts. Congenital anomalies include accessory ostia, complete or segmental tubal agenesis, and several embryonic cystic remnants. The most common is a small, benign cyst attached by a pedicle to the distal end of the fallopian tube—the hydatid of Morgagni. In other cases, benign paratubal cysts may be of mesonephric or mesothelial origin. Last, in utero exposure to DES is associated with various tubal abnormalities. Of these, short, tortuous tubes or ones with shriveled fimbria and small ostia are linked to infertility (DeCherney, 1981).