When genetics are ruled out
Issues that are top of mind when we lack genetic information or when genetic causes are ruled out include maternal metabolic disorders (uncontrolled diabetes, obesity, uncontrolled thyroid disease), environmental exposures (smoking), uterine abnormalities, and antiphospholipid syndrome.
Thorough evaluation of the uterine cavity after recurrent first trimester miscarriage – or after any second trimester loss – is too often a missing element of investigation. It is a vital component of the evaluation, and information about uterine structure is easily obtained.
A saline infusion sonogram (SIS) allows us to look at the external contour of the uterus, assess the myometrium for muscular abnormalities, visualize the uterine lining, and assess uterine orientation. Performed in the nonpregnant state, and ideally coupled with 3D technology, this relatively simple test can identify congenital uterine anomalies, intracavitary abnormalities (such as fibroids, polyps, or synechiae) which can surgically be removed prior to another pregnancy, a retroverted uterus that may be predisposed to incarceration during pregnancy, and other potentially impactful conditions, such as adenomyosis.
Structural anomalies
Congenital uterine anomalies are associated with first trimester miscarriage, second trimester pregnancy loss, and preterm birth. A uterine septum is of particular concern for early miscarriage, as the early embryo can implant on the relatively avascular septum.
Other congenital uterine anomalies (bicornuate, didelphys, unicornuate) can be associated with concomitant cervical structural abnormalities leading to cervical insufficiency and/or result in pathologic uterine stretch of a space-limited cavity, leading to midtrimester loss or preterm birth. The diagnosis of these anomalies is an important part of the evaluation of pregnancy loss, as it can guide monitoring in future pregnancies, or can be surgically corrected, as in the case of a uterine septum, significantly improving pregnancy outcomes.
A short cervix can result either congenitally or from injury or trauma and may also be associated with cervical insufficiency and miscarriage. It can be evaluated and monitored by ultrasound and, in some cases, treated by surgical cerclage. Pregnancy losses due to cervical insufficiency usually occur after 16 weeks of gestation and frequently are associated with intra-amniotic infections.
Incarcerated uterus and adenomyosis
Other uterine factors that can contribute to pregnancy loss and that are largely underdiagnosed or undiagnosed are an incarcerated retroverted uterus and adenomyosis.
Martin R. Chavez, MD. NYU Long Island School of Medicine
(Left image) Incarcerated retroverted uterus at 14 weeks gestation. Note the anteriorly displaced and compressed cervix and cervical canal (dotted yellow line) and the fundus wedged posteriorly (white arrow). The first impression is that the placenta is posterior (blue arrow) and the fetus is cephalic. (Right image) The same pregnancy after correction of the incarcerated uterus. Note the placenta is actually anterior (blue arrow) and the fetus is breech.
Most of the time, a retroverted uterus naturally assumes an anteverted position by the late first trimester or early second trimester, allowing for continued growth of the uterus and developing fetus. In approximately 10% of cases, however, the retroverted uterus becomes “stuck” or incarcerated in the posterior pelvis. This is more likely if there are large uterine fibroids or in the presence of pelvic adhesions due to endometriosis or previous pelvic surgery.
When this occurs, the fundus is wedged on the sacral promontory (may cause pelvic discomfort and constipation) and the cervix is markedly displaced anteriorly under the pubic symphysis (causing bladder outlet obstruction and urinary retention).
It is critical that ob.gyns. and emergency medicine providers are aware of this condition, which typically presents between 12 and 16 weeks’ gestation. The most frequent complaint is lower abdominal discomfort due to distended bladder and inability to void, which usually leads to bladder catheterization with drainage of large amounts of urine. An incarcerated uterus can predispose to pregnancy loss during this time (few other conditions cause loss during this time window), presumably due to impaired uterine artery blood flow.
Once the diagnosis is made, uterine incarceration may be corrected by elevating the gravid uterus out of the pelvis either manually, or by using a transvaginal ultrasound probe. (The latter minimally invasive approach was described in March at the American Institute of Ultrasound in Medicine’s annual conference by Martin Chavez, MD, and coinvestigators. More invasive approaches are rarely required but include CO2 intraperitoneal insufflation, as used prior to laparoscopy, or laparotomy.
The later in gestation the condition is allowed to persist, the less likely correction will be possible due to the enlarging fundus. Correction between 14 and 16 weeks, or earlier if symptoms develop, is recommended.
Martin R. Chavez, MD. NYU Long Island School of Medicine
Retroverted uterus demonstrating marked asymmetry of anterior (A) and posterior (P) uterine walls, in addition to heterogeneous uterine architecture, consistent with adenomyosis.
Adenomyosis, another poorly understood condition impacting pregnancy outcomes, has been associated with increased rates of miscarriage after in vitro fertilization (in addition to lower implantation rates); a meta-analysis published almost a decade ago found a risk ratio of miscarriage of 2.12 (95% confidence interval, 1.2-3.75) in women with adenomyosis versus those without (Hum Reprod. 2014 May;29[5]:964-77). However, outside of reproductive endocrinology, its impact on pregnancy outcomes in the obstetrical literature is not well recognized.
Although more research is necessary, we believe that adenomyosis should be considered a risk factor for pregnancy loss in the second trimester. The presence of endometrial glands within the myometrium, predisposing for an inflammatory environment, can lead to abnormal implantation, poor uterine distensibility, sterile inflammation, and early cervical insufficiency. As the prevalence of adenomyosis increases with age and maternal ages are increasing, this is an important condition to consider.
Diagnosis is typically made with MRI (although pathology of a hysterectomy specimen is the gold standard). Ultrasound findings consistent with adenomyosis are not routinely assessed and have not been studied in a gravid uterus. Nonetheless, a heightened sense of awareness about this possible contributor to pregnancy loss is very important.