Our cohort had many associated clinical anomalies: 3 confirmed trisomy 21 and 1 probable trisomy 21, 2 genetic disorders, and 10 major adverse outcomes, 5 of which were grave. Although we studied a small cohort, we conclude that an enlarged cavum septi pellucidi or cavum vergae warrants consideration of genetic counseling, which may include noninvasive prenatal testing (cell-free DNA), amniocentesis with microarray testing, or both.

Contemporaneous Zika virus (ZIKV) strains can cause congenital Zika syndrome (CZS). Current ZIKV clinical laboratory testing strategies are limited and include IgM serology (which may wane 12 weeks after initial exposure) and nucleic acid testing (NAT) of maternal serum, urine, and placenta for (+) strand ZIKV RNA (which is often transient). The objectives of this study were to determine if use of additional molecular tools, such as quantitative PCR and microscopy, would add to the diagnostic value of current standard placental ZIKV testing in cases with maternal endemic exposure and indeterminate testing. ZIKV RNA was quantified from dissected sections of placental villi, chorioamnion sections, and full cross-sections of umbilical cord in all cases examined. Quantitation with high-resolution automated electrophoresis determined relative amounts of precisely verified ZIKV (74-nt amplicons). In order to localize and visualize stable and actively replicating placental ZIKV in situ, labeling of flaviviridae glycoprotein, RNA ISH against both (+) and (–) ZIKV-specific ssRNA strands, and independent histologic examination for significant pathologic changes were employed. We demonstrate that the use of these molecular tools added to the diagnostic value of placental ZIKV testing among suspected cases of congenital Zika syndrome with poorly ascribed maternal endemic exposure.

OBJECTIVE: There is growing evidence that microbial dysbiosis plays a role in obesity, insulin resistance, chronic inflammation and adverse perinatal outcomes. Polycystic ovary syndrome (PCOS) is a condition of hyperandrogenism, oligomenorrhea and polycystic ovarian morphology. The etiology of PCOS is not yet discerned, and there is potential for the microbiome to play a role in the pathogenesis of the disorder. In this study, we sought to characterize how androgens and diet could modulate the microbiome and associate this with fertility outcomes in our model of PCOS. STUDY DESIGN: Prior studies in rhesus macaques demonstrate exposure to testosterone (T) at adolescence followed by a westernstyle diet (WSD) recapitulates features of PCOS. In this study, juvenile females were treated with subcutaneous cholesterol (control) or T implants beginning at menarche, and fed either a standard (14% of calories from fat) or WSD (36% of calories from fat). This created 4 cohorts: (1) control (C), (2) T alone, (3) WSD alone and (4) T+WSD (n¼10/group). Anal samples were collected at baseline plus after 3,6,12 and 18 months of treatment. Additionally, samples were collected from the vagina and cervix during menses, follicular and luteal phases of the uterine cycle. DNA was extracted and subjected to 16S sequencing. The animals were then mated and fertility and fecundity were recorded. RESULTS: Beta diversity analysis demonstrated that the microbiome of the GI tract is altered by WSD (p¼0.001), but not T (p0.52). Additionally, we demonstrate that the cervicovaginal microbiomes vary over the menstrual cycle in C animals (p¼0.012). This menstrual cycle variation was pattern was abrogated with T (p¼0.24). Beta diversity analysis of reveals a statistically different microbiome in the genital tract of each cohort (p¼0.001). Furthermore, when females were mated, the control animals and WSD animals achieved a 70% pregnancy rate. Conversely, the T treated animals achieved a 40% pregnancy rate and the T+WSD animals had a 33% pregnancy rate with 2/3 pregnancies atypical. CONCLUSION: We show that both WSD and T distinctly affect the cervicovaginal microbiome. Dysbiosis is distinct in a group that is subfertile and has increased atypical pregnancy rates. We hypothesize that the dysbiosis of the genital tract microbiome may play a role in adverse fertility and pregnancy outcomes seen with PCOS.