Reprod. Med., Volume 3, Issue 1 (March 2022) – 6 articles

Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m², 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies. Full article

Tetrasomy 9p is a chromosomal disorder characterized by the presence of a supernumerary chromosome. This rare abnormality exhibits a broad phenotypic variability and is not clearly distinguishable from other more frequent aneuploidies in the prenatal setting. We present two prenatal cases with dissimilar phenotypes, one with solely increased fetal nuchal translucency and one with multiple congenital anomalies, and discuss prior studies. These cases illustrate the difficulty of prenatally diagnosing this condition based on phenotypic information alone. We conclude that invasive prenatal diagnosis with (molecular) karyotyping is the best choice for the prenatal detection of tetrasomy 9p. Full article

Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease caused by transplacental passage of maternal circulating anti-Ro/SSA and anti-La/SSB antibodies which can bind to fetal cardiac tissue, damaging conduction tissues by inflammation and fibrosis. Approximately 2% of pregnancies with positive anti-Ro antibodies will be complicated by fetal atrioventricular block and the risk of recurrence in subsequent pregnancies is 10 times higher. We report a case of a clinically asymptomatic patient diagnosed with anti-Ro antibodies who had two pregnancies complicated by CHB with different outcomes. Despite preventive treatment with hydroxychloroquine (HCQ) from 6 weeks of pregnancy onward, the fetus developed second to third degree CHB. Dexamethasone was added. The pregnancy evolved to near-term with persistent intermittent CHB. It is not clear how pregnancies with recurrent fetal CHB despite prophylaxis with HCQ should be managed and there is a need for controlled studies to answer the remaining questions in relation to this subject. Full article

There is no report on preimplantation phase endometrial transcriptomics in natural conception cycles of primates. In the present study, the whole-genome expression array of endometrium on Days 2, 4, and 6 post-ovulation (pov) in proven natural conception (Group 1; n = 12) and non-mated, ovulatory (Group 2; n = 12) cycles of rhesus monkeys was examined, compared, and validated. Of fifteen (15) genes showing differential expression (>2-fold; pFDR < 0.05), six genes (CHRND, FOXD3, GJD4, MAPK8IP3, MKS1, and NUP50) were upregulated, while eight genes (ADCY5, ADIPOR1, NNMT, PATL1, PIGV, TGFBR2, TOX2, and VWA5B1) were down regulated on Day 6 pov as compared to Day 2 pov in conception cycles. On Day 6 pov, four genes (ADCY5, NNMT, TOX2, and VWA5B1) were down regulated, and AVEN was upregulated in conception cycles compared with the non-conception cycle. These observations were orthogonally validated at protein expression level. Group-specifically expressed unique genes in conception cycles influence the process of induction of immune-tolerance, while the genes expressed in both groups influence processes of protein targeting and metabolism. A triad of timed-actions of progesterone, seminal plasma, and preimplantation embryo putatively regulate several input molecules to CREB, NF-kB, and STAT regulatory networks during secretory phase towards evolution of endometrial receptivity in the rhesus monkey. Full article

Gestational diabetes mellitus (GDM) complicates between 5 and 12% of pregnancies, with associated maternal, fetal, and neonatal complications. The ideal screening and diagnostic criteria to diagnose and treat GDM have not been established and, currently, diagnostic use with an oral glucose tolerance test occurs late in pregnancy and produces poor reproducibility. Therefore, in recent years, significant research has been undertaken to identify a first-trimester biomarker that can predict GDM later in pregnancy, enable early intervention, and reduce GDM-related adverse pregnancy outcomes. Possible biomarkers include glycemic markers (fasting glucose and hemoglobin A1c), adipocyte-derived markers (adiponectin and leptin), pregnancy-related markers (pregnancy-associated plasma protein-A and the placental growth factor), inflammatory markers (C-reactive protein and tumor necrosis factor-α), insulin resistance markers (sex hormone-binding globulin), and others. This review summarizes current data on first-trimester biomarkers, the advantages, and the limitations. Large multi-ethnic clinical trials and cost-effectiveness analyses are needed not only to build effective prediction models but also to validate their clinical use. Full article