Structural anomalies

Structural anomalies of the uterus, cervix and vagina are the most common abnormalities of sexual differentiation seen in women. They arise from embryologic abnormalities of Müllerian system development (Chapters 5 and 6). The most severe form involves complete absence of the reproductive tract, including the vagina, uterus and fallopian tubes. Such agenesis of the Müllerian system is known as Mayer–Rokitansky–Kuster–Hauser syndrome, and is the second most common cause of primary amenorrhea (Chapter 30).

The remainder of the anomalies result from failure of the Müllerian system to fuse in the midline or to remodel in the midline after fusion to form a single uterine cavity (Fig. 27.1). The most dramatic form of fusion anomalies occurs when the Müllerian ducts fail to fuse along their entire length, resulting in the formation of two vaginas, two cervices and two separate uterine horns (double uterus or uterus didelphys). More commonly, only the upper portion of the uterus fails to fuse. The uterine body may then remain separated as two horns (bicornuate uterus or uterus bicornus) or, in milder cases, a dimple may be noted in the contour of the uterine fundus (arcuate uterus). Occasionally, only one side of the Müllerian system will develop, resulting in a hemi-uterus and a single fallopian tube (unicornuate uterus or uterus unicornus).

Failure to resorb the midline of the Müllerian ducts after fusion typically results in a uterine septum. A septum may be complete, running from the cervix to the fundus, or incomplete, involving only the uterine fundus (subseptate uterus). Occasionally, the vagina canalizes improperly and a vaginal septum will occur. This can occur in isolation or in conjunction with a uterine anomaly. Vaginal septa can be either longitudinal or horizontal. The longitudinal septum is reminiscent of those uterine anomalies resulting from failure of the Müllerian midline to resorb. Horizontal vaginal septa are thought to represent a failure of the vaginal plate to resorb at the site where it fuses with the Müllerian ducts.

Many women with structural anomalies of the reproductive tract are asymptomatic and never diagnosed. Others with Müllerian tract abnormalities may present with primary amenorrhea, recurrent miscarriages, preterm delivery and breech presentation at term. Because the mesonephros is closely involved in directing the development of the internal genitalia, the finding of a uterine anomaly should prompt an evaluation of the urinary system for an accompanying anomaly.

Exposure to diethylstilbestrol

In utero exposure to diethylstilbestrol (DES) occurred in individuals born between 1940 and 1971 whose mothers were given the synthetic estrogen in the hope of preventing a miscarriage. DES was subsequently shown to cause congenital abnormalities in women and, to a lesser degree, in men. The most frequently seen abnormalities in women are abnormally shaped cervices. These cervices have been described as coxcomb, hooded or hypoplastic. The uterine musculature may also be abnormally formed in DES-exposed women such that the uterine cavity assumes a T-shape on hysterosalpingography or saline-infusion sonohysterography. DES appears to cause these abnormalities via inappropriate activation of estrogen-dependent genes involved in differentiating the cervix and upper third of the vagina from the lower vagina. This results not only in the structurally abnormal cervices and uteri, but also in persistence of cervical glandular epithelium in the vagina (vaginal adenosis). In utero DES exposure is associated with an increased risk of reproductive failure, including infertility (likely from failed implantation), recurrent pregnancy loss and preterm delivery. DES daughters are also at increased risk for malignancies, specifically clear cell adenocarcinoma, arising in sites of vaginal adenosis. This is thought to result from exposure of the ectopic cervical glandular-type epithelia in the vagina to neoplastic inducers not usually accessible to the upper reproductive tract.

Occasionally, clinicians will observe cervical and uterine abnormalities that look exactly like those caused by in utero DES exposure in women never exposed to DES.