P-679 The impact of polycystic ovary syndrome (PCOS) on placental pathology among singleton livebirths conceived following in-vitro fertilization (IVF) or ovulation induction/intrauterine insemination (OI/IUI) treatments
Authors: Kavelidou M , Minis E , Jiang V  S , Cherouveim P , Dimitriadis I , James K , Bormann C  L , Roberts D  J , Souter I 
Published: July 2024

Abstract

Study question
Are there differences in placenta pathology between PCOS and non-PCOS infertility diagnosis among singleton livebirths conceived following either IVF or OI/IUI treatments?

Summary answer
PCOS diagnosis when compared to non-PCOS exhibits distinctive associations within the anatomic and vascular spectrum of placental pathology.

What is known already
Pregnancies of women with PCOS are at higher risk for maternal and neonatal morbidity. Available studies suggest a possible association of PCOS with hypoxia-induced placental findings among natural conceptions, and a possible role of chronic, low-grade inflammation on decidualization, trophoblast invasion, and placental vascularization. Given the high prevalence of PCOS among women seeking fertility treatments there is significant interest in human placental research. Nevertheless, the impact of PCOS on placental pathology among singleton livebirths conceived with fertility treatments remains unclear.

Study design, size, duration
Retrospective review of data from 1398 singleton livebirths with available placenta pathology. All pregnancies were conceived following fertility treatments (IVF:1004, OI/IUI: 394) at an academic fertility center and were delivered at the same hospital between 01/2004 and 04/2022. 1196 patients had an infertility diagnosis other than PCOS (uterine factor excluded) and 193 had been diagnosed with PCOS (based on Rotterdam criteria). Placenta pathology (classified as below) was compared between PCOS and non-PCOS patients.

Participants/materials, setting, methods
Placental findings were reviewed by one expert pathologist and classified further as anatomic, inflammatory, infectious, and vascular [including any features of fetal(FVM) or maternal(MVM) vascular malperfusion], using the Amsterdam Workshop Consensus definitions.
Primary outcomes: anatomic, inflammatory, infectious, and vascular.
Parametric/non-parametric tests were used as appropriate. Adjusted odds ratios(adjOR) with 95% confidence intervals (95%CI) were calculated utilizing logistic regression, controlling for potential confounders. Subanalyses were performed separating IVF from OI/IUI-conceptions, and fresh from frozen embryo transfers(FET).

Main results and the role of chance
PCOS compared to non-PCOS patients were younger, with higher BMI and AMH [mean (SD): 32.9(3.5) vs 35.1(3.8) years, p &lt; 0.001; 26.1(5.5) vs 24.8(5.5)kg/m2, p = 0.003; 9.1(5.8) vs 3.5(3.4)ng/ml, p &lt; 0.001, respectively].
Overall, neither unadjusted rates (35.2% vs 28.8%, p:0.072; 15.9% vs 11.8%, p = 0.115; 21.8% vs 20.0%, p = 0.568; 51.0% vs 57.3%, p = 0.103, PCOS vs. non-PCOS, respectively), nor adjOR (95%CI) [1.02(0.94-1.1), 1.01(0.95-1.08), 1.02(0.94-1.09), 0.96(0.88-1.05), non-PCOS: ref] showed any differences between groups in anatomic, inflammatory, infectious, and vascular abnormalities, respectively.
When separating IVF from OI/IUI-conceptions, and fresh transfers from FETs, adjOR(95%CI) revealed no differences between groups in anatomic, inflammatory, and infectious abnormalities [OI/IUI: 1.01(0.87-1.16), 1.0(0.88-1.13), 1.0(0.88-1.13); Fresh ET: 1.01(0.9-1.14), 1.02(0.95-1.1), and 0.95(0.85-1.05); FET: 1.16(0.96-1.4), 1.0(0.87-1.16), and 1.11(0.93-1.33), for anatomic, inflammatory, and infectious abnormalities, respectively, non-PCOS: ref].
Interestingly, a lower rate of vascular abnormalities was noted among PCOS patients in OI/IUI [adjOR(95%CI): 0.83(0.73-0.96)], but not among fresh or FET cycles [adjOR(95%CI): 1.05(0.91-1.19), and 0.97(0.8-1.18), respectively]. In FET cycles, within vascular abnormalities, lower rates of high grade FVM among PCOS patients were noted [adjOR(95%CI): 0.96(0.93-0.99)]. Furthermore, and although anatomic abnormalities did not differ between groups, a lower incidence of single umbilical artery [adjOR(95%CI): 0.98(0.96-0.99)] was noted among PCOS patients in IVF cycles.

Limitations, reasons for caution
The study is limited by its retrospective design and focuses on an infertile population undergoing treatments, limiting generalizability. Comparisons with PCOS patients conceiving naturally may provide meaningful insights. Variability among PCOS phenotypes, and other environmental, and lifestyle factors might also alter a patient’s individual pregnancy risk for placental abnormalities.

Wider implications of the findings
PCOS may impact placental pathology in a distinct way, within the anatomic and vascular spectrum, which might differ from that of other infertility causes and might be further altered by the treatment protocol. Our study adds to the limited human placental research specific to pregnancy of women with PCOS.

Trial registration number
Not Applicable