49 Does fetal sex influence placental abnormalities in polycystic ovary syndrome (PCOS) patients conceiving with fertility treatments (FT)?

Abstract Abstract: Introduction Sex-specific differences in fetal-placental signaling are well established. Female (F) fetuses favor glucocorticoid-regulated pathways, enhancing placental reserve but limiting growth. Male (M) fetuses prioritize androgen-driven signaling, promoting growth at the cost of adaptability. In PCOS, an androgen-mediated condition, these adaptations may be exaggerated, potentially altering placental histopathology. Methods We retrospectively reviewed placental pathology data from singleton livebirths (1/2004–4/2022) conceived with FT (n = 1381). PCOS patients (Rotterdam criteria; n = 181) were grouped by fetal sex (M = 90; F = 91). Placental findings were categorized as anatomic, inflammatory, infectious, or vascular by a blinded perinatal pathologist using Amsterdam Workshop Consensus definitions. Comparisons were made using parametric/nonparametric tests. Logistic regression calculated crude and adjusted odds ratios (aOR), controlling for maternal age, BMI, race, gestational age, FT type, and gestational diabetes (GDM). Results Baseline characteristics of PCOS patients who delivered M vs F fetuses did not differ significantly [age, mean (SD)—M: 32.8 (3.1) vs F: 33.0 (3.8), p = 0.75; BMI— M: 26.2 (5.6) vs F: 26.2 (5.7), p = 0.89; nulliparity, n (%)—M: 67 (74.4%) vs F: 75 (83.3%), p = 0.14; FT—Ovulation Induction /Intrauterine Insemination—M: 40(44%) vs F: 48 (53.3%); In Vitro Fertilization—M: 51 (56%) vs F: 42 (46.7%), p = 0.21; GDM—M: 14 (15.4%) vs F: 8 (8.9%), p = 0.18]. There were no differences in anatomic, infectious, or vascular abnormalities by fetal sex in crude or adjusted models. Inflammatory abnormalities—villitis of unknown etiology, deciduitis, and intervillositis—were more frequent in F placentas on crude analysis [F: 20 (23%) vs M: 9 (9.9%), OR 1.14 (95% CI 1.02–1.27); p = 0.01], but not after adjustment [aOR 1.07 (95% CI 0.91–1.26); p = 0.4]. Conclusion This study suggests that fetal sex does not significantly impact placental pathology in PCOS pregnancies. These findings provide reassurance that fetal sex differences may not be a major factor in placenta-mediated pregnancy complications in PCOS patients undergoing FT. Further research should explore the potential influence of androgen exposure on placental function and long-term fetal outcomes in this population.