Impact of repeated ovulation induction and superovulation on ovarian reserve and early embryo development in obese and PCOS-like mouse models.

Abstract

CONTEXT: Women with obesity or polycystic ovary syndrome (PCOS) often require repeated ovulation induction (OI) due to ovulatory dysfunction and infertility. However, the cumulative effects of repeated stimulation on ovarian function and embryo development remain poorly understood. AIMS: The present study aimed to understand the consequences of repeated OI and/or repeated superovulation (SO) on preimplantation embryonic development in obese (high-fat diet-induced) and PCOS (high-fat diet and dehydroepiandrosterone-induced) mouse models. METHODS: Control (without any metabolic disorder), obese, and PCOS mice were divided into three experimental groups. The mice in one round of superovulation (SO1) were injected with 5 IU intraperitoneal (i.p.) injection of pregnant mare serum gonadotropin, followed by 10 IU of human chorionic gonadotropin 48 h later. In the repeated superovulation (SO3) group, mice were subjected to three rounds of superovulation with a gap of 9 days between each superovulation. Mice in the OI3 + SO3 group were administered with three doses of CC (50 mg/kg body weight, i.p., gap of 9 days between each CC injection), followed by three rounds of superovulation. KEY RESULTS: Both single and three rounds of superovulation resulted in decrease in primordial follicles and a moderate increase in atretic follicles in obese and PCOS mice. Reduction in the number of ovulated oocytes, increased rate of abnormal fertilization, decrease in blastocyst rate and elevated DNA damage in blastocysts were observed in in vitro fertilization-derived embryos. CONCLUSIONS: These findings demonstrate compromised embryonic development following repeated ovarian stimulation. IMPLICATIONS: The study highlights need for mild ovarian stimulation strategies in metabolically compromised patients undergoing infertility treatments.