Amy Sullivan

Recurrent fetal aneuploidy and Recurrent miscarriage

OBJECTIVE: Some investigators have found a high frequency of abortus aneuploidy in women with recurrent miscarriage, suggesting the possibility of recurrent aneuploidy as a cause of recurrent miscarriage. Others contend that aneuploidy is not a cause of recurrent miscarriage. The purpose of this study was to investigate the relationship between fetal aneuploidy and recurrent miscarriage by estimating whether fetal aneuploidy is more common in patients with recurrent miscarriage than in patients with sporadic miscarriage METHODS: Recurrent miscarriage cases (n = 135) included women who had a subsequent miscarriage in which an abortus karyotype was obtained. Controls (n = 150) were patients experiencing a sporadic miscarriage who had fetal karyotypes performed as part of a study to assess the utility of abortus tissue for transplantation. Karyotype analysis was performed using standard G-banding techniques. RESULTS: Abortuses from 122 cases and 133 controls were successfully karyotyped. Thirty-one (25.4%) abortuses from cases and 56 (42.1%) from controls were aneuploid (odds ratio 0.47, 95% confidence interval 0.27–0.80). Aneuploid abortuses occurred in 20% of cases and 25% of controls, aged 20–29 years, 19% of cases and 24% of controls, aged 30–34 years, 35% of cases and 47% of controls, aged 35–39 years, and 50% of both cases and controls, aged 40 years or older (not significant). Of 30 cases in whom 2 or more miscarriages were karyotyped, 3 (10%) had aneuploidy in each abortus. CONCLUSION: In our population of recurrent miscarriage patients, abortus aneuploidy occurred significantly less often than in sporadic miscarriages. The rate of aneuploidy in this study was considerably lower than reported in other studies. If recurrent aneuploidy contributes to recurrent miscarriage, it does so in only a small number of patients. LEVEL OF EVIDENCE: II-2

Poor obstetric outcome in subsequent pregnancies in women with prior fetal death.

OBJECTIVE: Patients with recurrent first-trimester spontaneous abortion have been the subject of intensive investigation. However, relatively little is known about second- and third-trimester pregnancy loss. Thus, it is difficult for clinicians to optimally counsel, evaluate, and manage women with previous unexplained fetal death. Our objective was to ascertain the outcome of subsequent pregnancies in patients with prior fetal death. METHODS: Subjects were identified from patients referred for evaluation of fetal death (occurring at ≥ 10 weeks of gestation) and having at least one subsequent pregnancy. Patients with antiphospholipid antibodies were excluded. Logistic regression analysis was performed to determine the association of clinical variables with pregnancy outcome. RESULTS: Two hundred thirty subjects met inclusion criteria. Up through the time of their first fetal death, these women had a total of 721 pregnancies, resulting in 268 (37%) live births, 230 (32%) fetal deaths, and 200 (28%) spontaneous abortions. In total, these women had 839 subsequent pregnancies, resulting in 202 (24%) live births, 209 (25%) fetal deaths, and 372 (44%) spontaneous abortions. Univariate logistic regression analysis identified older age at pregnancy (P = .009, odds ratio 0.63, 95% confidence interval 0.42–1.03) and treatment with low-dose aspirin (P = .001, odds ratio 0.41, 95% confidence interval 0.25–0.68) to be associated with a decreased risk for subsequent pregnancy loss. CONCLUSION: Women with prior fetal death are at high risk for subsequent pregnancy loss and recurrent fetal death, with fewer than 25% of pregnancies resulting in surviving infants. These data underscore the need for additional research into the pathophysiology and prevention of recurrent fetal death. LEVEL OF EVIDENCE: II-2

Pregnancy outcome in recurrent miscarriage patients with skewed X chromosome inactivation.

OBJECTIVE To analyze X inactivation in women with recurrent miscarriage to estimate whether skewed X inactivation is associated with recurrent miscarriage and whether it predicts next pregnancy outcomes. METHODS A multicenter study was performed. A power calculation determined that 101 patients were needed to detect a difference in skewed X inactivation between patients and controls. Patients were entered into a prospective trial of mononuclear-cell immunotherapy and subsequently tested for skewed X inactivation. Age-matched controls had one live birth and no prior miscarriages. Results from our X inactivation assay were compared with those from an independent genetics laboratory. RESULTS Greater than 75% skewing was seen in 22.6% of patients and 26.5% controls (P = .52). Greater than 90% skewing was seen in 6.6% of patients and 3.9% of controls (P = .77). There were 19.8% of primary aborters and 32% of secondary aborters with greater than 75% skewed X inactivation (P = .38). There were 4.9% of primary aborters and 12.0% of secondary aborters with greater than 90% skewed X inactivation (P = .27) Neither greater than 75% nor greater than 90% skewed X inactivation impacted next pregnancy outcomes (odds ratios = 0.87 [95% confidence interval (CI) 0.34, 2.3] and 1.4 [95% CI 0.27, 7.5], respectively). Results of the exchange of samples with an independent laboratory were highly correlated (α = 0.987, P < .001, coefficient of variation = 5.5%). CONCLUSION Skewed X chromosome inactivation is not associated with recurrent miscarriage. A patients X chromosome inactivation status does not predict next pregnancy outcome. Our assay correlates with another experienced laboratory.

Delivery of monochorionic twins in the absence of complications: analysis of neonatal outcomes and costs

OBJECTIVE We sought to estimate the optimal time to deliver uncomplicated monochorionic-diamnionic (MCDA) twins. STUDY DESIGN Data were retrospectively obtained from twin pregnancies from 2000 through 2009. The gestational week-specific prospective perinatal mortality risk was calculated. A cohort of MCDA twins with nonindicated deliveries was analyzed separately. Neonatal outcomes and costs were compared between MCDA twins with nonindicated deliveries born at specific weeks of gestation, and those born the subsequent week. RESULTS There were 5894 dichorionic-diamnionic twins and 1704 MCDA twins. After 28 weeks, the gestational week-specific prospective risk of perinatal mortality did not differ between groups. There were 948 MCDA twins with nonindicated deliveries. Until 37 weeks, the risk of severe neonatal morbidity, perinatal mortality, and hospital costs were greater for fetuses delivered compared to fetuses born in a subsequent week. CONCLUSION To optimize neonatal outcome and decrease hospital costs, MCDA twins should not be delivered <37 weeks unless medically indicated.

The Factor V Leiden and the G20210A Prothrombin Gene Mutations are Rare in Women with Fetal Death

Problem:  To determine if there is an association between two commonly inherited thrombophilias, the factor V Leiden and the G20210A prothrombin mutations, and fetal death.

The Aryl Hydrocarbon Receptor Nuclear Translocator Gene Polymorphism in Patients With Recurrent Miscarriage

Objective  The human aryl hydrocarbon receptor nuclear translocator gene (ARNT) is crucial for embryonic development. Knockout of ARNT is embryonic lethal. We thus hypothesized that some cases of recurrent miscarriage (RM) may be due to a polymorphism in the ARNT gene.

Thyroid Hormone Replacement During Pregnancy

Thyroid metabolism plays an important role in reproductive processes and fetal development. Aberrant thyroid function can have profound effects on both maternal and fetal health. Hypothyoroidism is relatively common during pregnancy, but the diagnosis may be missed and treatment often problematic for several reasons. First, many of the classic signs and symptoms are considered typical of pregnancy. Second, the usually straightforward interpretation of thyroid function laboratory tests is made difficult by the physiologic effects of pregnancy on thyroid metabolism Finally, obstetric abnormalities, such as gestational trophoblasic disease and hyperemesis gravidarum, may have profound effects on thyroid function.