Uterine Factors and Recurrent Pregnancy Loss
Patients who experience one or more miscarriages seek reasons why they suffered early pregnancy loss and often find resolution and healing in obtaining answers. While genetic abnormalities in embryos are the most common cause of single miscarriages and likely recurrent losses, anatomical defects of the uterus are common and are believed to account for 10%-20% of recurrent pregnancy loss (RPL). Some uterine abnormalities form during embryological development (congenital) and others during a woman’s lifetime (acquired). By the eighth week of pregnancy, the embryo forms a pair of ducts that give rise to the uterus, fallopian tubes and upper vagina. The uterus originates as two separate, solid masses (often referred to as “horns”) that fuse together to form a single solid mass. Once this occurs, tissue within the mass is resorbed (canalization) to form a large inner cavity and the mature uterus.
Multiple congenital abnormalities exist and involve aberrations in fusion or growth of the two uterine horns, or in canalization. A didelphic, or double, uterus results from complete non- fusion of the two horns. A bicornuate uterus is one in which the uterine horns incompletely fuse leaving the horns separate at the top of the uterus. Absent formation of one of the horns results in a small, single-horned uterus (unicornuate uterus). The most common congenital uterine abnormality (septate uterus, or uterine septum ) results from the failure of the fused horns to fully canalize resulting in a wall of solid tissue extending from the top of uterus into the uterine cavity.
Studies suggest that fewer than 0.5% of women have congenital uterine abnormalities, but the prevalence may exceed 15% in women with RPL. Miscarriage rates are increased in women with unicornuate, bicornuate, and septate uteri, but not in women with didelphic uteri. Nearly half of pregnancies in women with unicornuate uteri end in miscarriage, and up to two-thirds of pregnancies in women with septate uteri. The uterine septum has a poorer blood supply than the surrounding uterine tissue, perhaps the primary reason it leads to miscarriages. A woman with a uterine septum has nearly three times the rate of miscarriage as a woman with a normal uterus. Women with uterine septae also have a higher rate of preterm labor and fetal growth restriction than women with normal uteri.
Uterine abnormalities acquired during a woman’s lifetime include benign smooth muscle tumors (leiomyomata, or fibroids), polyps, and scar tissue (adhesions). While all increase the risk of RPL, it is not clear how they do so. Interruptions in blood flow through the uterine vessels, inflammation of the inner uterine lining (endometrium), and a reduction in the capacity of the uterus are all possible causes.
Uterine fibroid tumors are the most common acquired uterine abnormality in women of all races. Fibroids develop in 30%-60% of non-black women and up to 80% of black women during their lifetimes. Fibroids are composed of smooth muscle cells and are benign in more than 99% of cases. They vary from a few millimeters to several centimeters, and can mainly occupy the uterine cavity (submucosal fibroids), the uterine muscle wall (intramural fibroids) or the outer wall and surface of the uterus (subserosal). Submucosal and intramural fibroids, but not subserosal fibroids, have been found in some studies to impact fertility. Some studies have shown a significant association between fibroids and single and recurrent miscarriages.
Polyps are benign growths within the uterine cavity containing both endometrial tissue and blood vessels. It is thought that polyps can induce inflammation in the uterine cavity. Like fibroids, polyps grow in response to reproductive hormones and can range in size from a few millimeters to a few centimeters. Polyps have been detected in up to 30% of women with infertility. The role of polyps in infertility and miscarriage is not clear from current studies.
Intrauterine adhesions, or scar tissue, results from prior infections, miscarriages, abortions, or other types of uterine surgery. Adhesions can affect a small part of the uterus or involve the entire endometrial surface resulting in loss of periods and infertility. While some studies have reported a higher incidence of adhesions in women with RPL than in women with normal reproductive outcomes, the contribution of adhesions to RPL has not been well-established.
Diagnosis of Uterine Abnormalities:
The structure of the uterus can be evaluated with a variety of tools including pelvic ultrasound, saline hysterosonography, hysterosalpingography, and hysteroscopy. During a saline hysterosonogram, saline is injected through the cervix into the uterus in order to separate the uterine walls and better visualize the uterine cavity during ultrasound. A hysterosalpingogram involves the injection of a special dye into the uterus to allow X-ray detection of uterine and fallopian tube abnormalities. Hysteroscopy is an operative procedure in which a thin telescope is inserted through the cervix into the uterus to allow direct visualization of the uterine cavity and for surgical correction of certain uterine abnormalities. MRI scans are helpful to accurately diagnose complex uterine abnormalities, and laparoscopy, direct telescopic visualization of the pelvic organs through small skin incisions, is useful for diagnosis and treatment in certain cases.
High quality studies on the effectiveness of septum removal (septoplasty) to reduce miscarriage rates are lacking. Although some women with uterine septae have full term pregnancies with no intervention, some studies have demonstrated a profound reduction in miscarriages in women with RPL who undergo septoplasty before the next pregnancy. In one study of women with RPL, the miscarriage rate dropped by more than 80% after septoplasty. In another study, fertility rates improved after septoplasty. The removal of uterine septae is performed using a hysteroscope and cutting device. No abdominal incisions are required.
No surgery has been found to reduce miscarriage rates in women with unicornuate uteri. Some women with this abnormality will have healthy live births, although the risk of preterm labor is increased.
In years past, a variety of surgical procedures were used to convert the bicornuate uterus to a normal-appearing uterus. As studies dialed to show a benefit of these procedures for reducing pregnancy loss, surgery is no longer performed to repair bicornuate uteri. Many women with bicornuate uteri will have full-term healthy babies.
As women with didelphic uteri do not appear to have an increased risk of miscarriages, current data do not support surgical correction.
Studies have shown that the removal of submucosal fibroids can significantly improve fertility rates, reduce the incidence of first trimester miscarriages, and improve live birth rates after both spontaneous conception and in vitro fertilization (IVF). There is insufficient evidence that removal of fibroids outside the uterine cavity reduces miscarriage rates – in these cases, surgery should be done only if a woman has pain or bleeding warranting surgical intervention, or if the fibroids are large enough to create obstetrical problems including preterm labor, hemorrhage or obstruction to vaginal delivery. Surgery to remove fibroids is called myomectomy. When fibroids are submucosal, myomectomy can be done by hysteroscopy. For intramural or subserosal fibroids, myomectomy is performed laparoscopically or by larger abdominal incisions.
Limited data show an increased clinical pregnancy rate following the removal of polyps (polypectomy) in infertile women undergoing intrauterine inseminations. Few studies have investigated the benefits of polypectomy in women with RPL. Most have failed to show a significant benefit of polypectomy in women with RPL. The general consensus of fertility experts is to do a polypectomy if polyp(s) is the only abnormal finding in an extensive RPL evaluation. The removal of large polyps (1 cm or greater) in the upper uterine cavity where most implantation occurs might be of more value than removing tiny polyps. Polypectomy is performed by hysteroscopic excision and/or scraping of the endometrial surface (dilatation and curettage).
Adhesions/ Intrauterine Scar Tissue
Few studies have compared miscarriage rates in women who have undergone hysteroscopy and breakage of adhesions (adhesiolysis) to women in whom no surgery was performed. Limited data show a reduction in miscarriage rates after adhesiolysis. This procedure is performed using hysteroscopy and microscissors. Hormone treatment is often given post-operatively to reduce new scar formation.
Overall, abnormalities of the uterus may result in impaired fertility and increased miscarriages. Any woman who has RPL should have a thorough diagnostic evaluation that includes an assessment of the uterine cavity.