Placental pathology and weight following Intrauterine Insemination (IUI) with or without ovarian stimulation (OS)

Ovarian stimulation (OS) alters the peri-implantation environment and may affect placentation. Therefore, our study aimed to compare placental pathology and PW among singleton live births conceived after IUI with gonadotropins (Gn), oral medications (OM; clomiphene/letrozole), or unstimulated/natural (Nat) cycles.

Retrospective review of 386 IUI(±OS) singleton live births with placental examination: Gn (n = 222), OM (n = 129), and Nat (n = 35). Outcomes were placental lesions (classified as anatomic, inflammatory, infectious, or vascular) and PW. Generalized estimating equations (GEE) estimated adjusted risk ratios (adjRR) for pathology, adjusted beta (adjβ), for PW, and their respective 95% confidence interval (95%CI), controlling for maternal age, BMI, race, PCOS diagnosis, gestational age at delivery, infant sex, and pregnancy complications (hypertensive disorders and diabetes). Sensitivity analyses included uncomplicated term livebirths and inverse probability weighting (IPW).

After multivariable GEE adjustment, OM was associated with higher odds of anatomic abnormalities compared with both Gn and Nat [adjRR (95% CI): 1.15 (1.02, 1.31) and 1.28 (1.05, 1.56), respectively], whereas Gn did not differ compared to Nat. In our sensitivity analyses, adjRR (95%CI) for anatomic lesions remained similarly more prevalent in OM compared to Nat [Uncomplicated: 1.21 (0.96, 1.52); IPW: 1.29 (1.02, 1.63)], while it was not significant compared to Gn [Uncomplicated: 1.09 (0.93, 1.29); IPW: 1.12 (0.97, 1.30)]. Inflammatory, infectious, vascular placental abnormalities, and PW remained comparable between groups in the main analysis and after the same restrictions.

Among IUI-conceived singleton births with placental evaluation, oral medications were associated with more anatomic placental abnormalities than gonadotropins or natural cycles, whereas PW did not differ by protocol.