Associations of Maternal Polyendocrine Metabolic Ovarian Syndrome with Offspring Ovarian Activity in Minipuberty.

OBJECTIVE

To study whether maternal PMOS is associated with altered ovarian activity in infant daughters during minipuberty.

DESIGN

Prospective, observational pregnancy and birth cohort: The Copenhagen Analgesic Study (COPANA), conducted at Copenhagen University Hospital - Rigshospitalet, Denmark (2020-2022).

SUBJECTS: Singleton pregnant women (n = 685) recruited at a median (IQR) gestational age of 13.7 weeks (12.8-15.0). Overall, 589 infants (302 girls) underwent examination during minipuberty at a mean age of 3.49 ± 0.44 months.

EXPOSURE: Maternal PMOS was self-reported based on a previous medical diagnosis, established by ovarian ultrasound (n = 8) or combined blood tests and ultrasound (n = 14). Overall, 298 girls with available information on maternal self-reported PMOS status (yes = 22, no = 276) were included in this study.

MAIN OUTCOME MEASURES: Ovarian and uterine morphology by transabdominal ultrasound scan and circulating levels of anti-Müllerian hormone (AMH), inhibin B, gonadotropins (immunoassays), steroid hormones (LC/MS-MS). Linear regression models were adjusted for maternal paracetamol and alcohol use during pregnancy, with sensitivity analysesfor maternal nicotine use.

RESULTS

Maternal self-reported PMOS was associated with increased offspring ovarian volume: 43.48% (0.14; 105.58) using adjusted models, p = 0.05. PMOS-exposed daughters also had higher AMH: 0.55 SDS (0.06; 1.04), p = 0.03, higher SHBG: 0.61 SDS (0.15; 1.07), p = 0.01, and reduced endometrial thickness: -0.03 cm (-0.06; -0.00), p = 0.04. Maternal characteristics, including pre-pregnancy body mass index, did not differ between groups.

CONCLUSION

Maternal PMOS was associated with larger ovarian volume and higher AMH levels in infant daughters, indicating that PMOS-related alterations in ovarian morphology and function may be evident already in early life.