Repeated Superovulation Accelerates Primordial Follicle Activation and Atresia

Area of Science:

• Reproductive Endocrinology
• Ovarian Physiology
• Assisted Reproductive Technologies (ARTs)

Background:

• Assisted reproductive technologies (ARTs) are crucial for treating infertility, often requiring ovarian stimulation.
• While ARTs are effective, the impact of multiple ovarian stimulation cycles on ovarian reserve remains understudied.
• Existing research highlights ARTs' adverse effects on women and offspring, but specific impacts on ovarian reserve are less clear.

Purpose of the Study:

• To investigate the effects of repeated ovarian superovulation on ovarian reserve.
• To analyze the molecular and cellular changes in the ovary following multiple stimulation cycles.
• To determine the impact on folliculogenesis and granulosa cell apoptosis.

Main Methods:

• Evaluation of ovarian reserve markers, including primordial follicle count and serum Anti-Müllerian hormone (AMH) levels.
• Gene expression analysis of primordial follicle activation (e.g., Foxo3, Akt, Rptor) and apoptosis (e.g., Bax, Caspase-3) in granulosa cells.
• Measurement of plasma levels of FSH, LH, and estradiol in response to repeated superovulation.

Main Results:

• Repeated superovulation significantly reduced primordial follicle numbers and serum AMH levels.
• Antral follicle count decreased, while genes related to primordial follicle activation and atretic follicle numbers increased.
• Plasma FSH, LH, and estradiol levels decreased, and apoptosis-related gene expression in granulosa cells increased.

Conclusions:

• Repeated ovarian superovulation negatively impacts ovarian reserve and folliculogenesis.
• The process disrupts the balance between granulosa cell survival and death, potentially through increased apoptosis.
• Findings suggest careful consideration of ovarian stimulation protocols in ART to mitigate long-term effects on fertility.