Recurrent Early Pregnancy Loss - 4 - Anatomic Causes
Early in the embryonic development of the female genital tract, the uterus begins as separate structures on both side of the pelvis. In normal circumstances, as development progresses, these separate structures move to the midline and fuse, forming a single uterus, cervix and vagina. In 1 out of every 200 to 600 women, this process is interrupted during some point in the developmental process. The congenital malformations that result from this are called ‘Mullerian duct abnormalities.’ These abnormalities can range from complete lack of fusion of the Mullerian duct, resulting in two completely separate uteruses (uterus didelphys) with cervixes (and sometimes two vaginas); a partial lack of fusion, resulting in a uterus with two cavities and a single cervix (bicornuate uterus); or a uterus that has a single cavity that is divided in the midline to varying degrees by a fibromuscular wedge of tissue (septate uterus).
Under some circumstances, only one of the embryological precursors for the genital tract will develop forming a single (usually smaller) uterus (unicornate uterus) and cervix which deviates to the side of its origin. The latter are frequently associated with urinary tract abnormalities, such as an absent kidney, usually on the side which did not have normal development of the Mullerian duct. Mullerian abnormalities result in smaller uterine cavities, fewer suitable implantation sites, and aberrations of vascularization (blood supply) that may contribute to both early and later pregnancy losses. Indeed, these abnormalities are frequently also accompanied by cervical incompetence which has been addressed in other posts. One other condition associated with a small, abnormally-shaped uterine cavity and high rate of unexplained first trimester losses is seen in women who were exposed to DES (diethyl stilbesterol) in utero. Fortunately, since the last DES used in reproductive age women was given in the early 1970’s, this is quickly becoming less of a problem.
The most common neoplasms (‘tumors’) of the uterus are fibroids (leiomyomata). These are characterized by an excessive proliferation of the smooth muscle cells and connective tissues that are normally present in the muscular wall of the uterus. The cause of fibroids is unknown. They are generally ‘benign’ (not cancer) and can be located just beneath the intraabdominal surface of the uterus (subserosal fibroids), within the muscular wall (intramural fibroids), or beneath the inner lining (endometrium) of the ueterus (submucosal). At times they can project either into the abdomen or into the uterine cavity on ‘stalks’ and these are referred to as ‘pedunculated fibroids.’ Uterine fibroids can distort and/or decrease the volume of the uterine cavity, compromise implantation or growth of the placenta by stretching and thinning the endometrium or by stealing blood supply, and if located in proximity to the cervix, may distort the internal cervical opening (os) sufficiently to cause cervical incompetence as well.
Endometrial polyps result from localized overgrowth (proliferation) of the endometrium and also produce a stalked projection into the uterine cavity. Both endometrial polyps and intrauterine fibroids (pedunculated or not), in addition to causing distortion of the uterine cavity, are often sites of chronic inflammation and/or infection and this may be the means by which they contribute to early pregnancy losses. Under these circumstances they may function as a ‘natural’ analog to an intrauterine device (IUD), by preventing proper implantation or disturbing the delicate immunologic balance of early pregnancy, interrupting the growth of the developing embryo.
During our surgical care for patients, we may also induce damage to the endometrium that can lead to recurrent pregnancy loss. These are classified under the ‘iatrogenic’ causes for recurrent pregnancy loss. For example, many patients who have early pregnancy losses (or who have undergone elective termination of pregnancy in the past) will undergo dilatation and curettage (D&C) procedures to complete the evacuation of the pregnancy tissues from the uterus. If a D&C is performed too aggressively, or if an intrauterine infection is present as either the cause or the result of a pregnancy loss at the time a D&C is performed, the result can be scarring of the endometrial cavity, termed Asherman’s syndrome. At times this scarring can be so extensive (especially if infection was present at the time of the procedure), the woman will stop having periods altogether. Damage to the endometrial cavity can also result during the surgical removal of endometrial polyps or intrauterine fibroids, even when these procedures are performed through an operating scope (hysteroscopy). Again, regardless of the cause, when such damage or scarring is present, the common threads of poor implantation sites, decreased blood supply, and inflammation can raise their ugly heads to interrupt early pregnancies on a repetitive basis...