Breaking Down Fertility Barriers: Study evaluates Role of High Dose Hormones in ART and Ovarian Function

Recent study examines the implications of multiple cycles of controlled ovarian stimulation (COS) using supraphysiologic hormone doses on ovarian reserve functions and clinical pregnancy outcomes in infertile women undergoing assisted reproductive technology (ART). With a focus on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the research interrogates the extent to which repeated COS cycles affect both ovarian function and pregnancy rates.

Research Methodology

Utilizing a retrospective analysis of 45,555 COS-IVF/ICSI cycles from 39,641 patients, the research sample was stratified based on the number of COS cycles (1 to 5). The primary indicators assessed included antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, as well as clinical pregnancy rates (CPR), live birth rates (LBR), and early miscarriage rates (EMR). Factors such as baseline hormone levels and patient characteristics including age and BMI were controlled to ensure clarity in the outcomes. Findings revealed that multiple COS cycles did not significantly detriment ovarian reserve function. Statistical comparisons indicated that while increasing cycle numbers correlated with variable CPR and LBR trends, age, BMI, endometrial thickness, and embryo-related factors exhibited a more pronounced influence on pregnancy outcomes. Specifically, the study highlighted that CPR and LBR tended to decline with more cycles, while EMR showed a corresponding increase; however, these changes were often inconclusive when controlling for age and other variables.

Implications of Results

The results of intra-group comparisons suggested that undergoing up to four COS cycles was associated with increased CPR and LBR, contradicting fears regarding the negative impact of such procedures on reproductive health. Conclusively, the study posits that while repeated COS may not inherently compromise overall fertility potential, clinicians should carefully consider the implications beyond the fifth cycle, encouraging patients to be informed about individual treatment paths. Despite the robust sample size and controlled conditions that enhance the validity of the findings, the study acknowledges potential biases such as selection and information bias inherent in retrospective designs. It emphasizes the need for further large-scale, prospective studies to fully elucidate the long-term effects of repeated COS on fertility and to refine clinical recommendations based on varied treatment experiences. These insights serve to support practitioners in devising effective ART strategies while ensuring patient safety and optimizing reproductive outcomes.

Key Points

- -Objective of the Study-: This research investigates the implications of multiple cycles of controlled ovarian stimulation (COS) on ovarian reserve functions and clinical pregnancy outcomes in women undergoing assisted reproductive technologies (ART), specifically through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

- -Methodology-: A retrospective analysis was conducted on 45,555 COS-IVF/ICSI cycles from 39,641 patients, stratifying the sample based on the number of COS cycles (ranging from 1 to 5). Key indicators measured include antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, clinical pregnancy rates (CPR), live birth rates (LBR), and early miscarriage rates (EMR), while controlling for factors like baseline hormone levels, patient age, and BMI.

- -Impact on Ovarian Reserve-: Findings reveal that multiple COS cycles do not significantly impair ovarian reserve function. Statistical analyses show limited detriment to AFC and AMH levels despite an increasing number of COS cycles.

- -Trends in Clinical Outcomes-: Although clinical pregnancy rates and live birth rates tended to decline with an increasing number of cycles, early miscarriage rates showed a corresponding increase. However, these trends were often inconclusive when accounting for variables such as age and other patient-specific factors.

- -Recommendations for Clinical Practice-: The study suggests that undergoing up to four COS cycles might be associated with improved CPR and LBR, countering concerns regarding the adversarial effects of COS on reproductive health. Clinicians are advised to weigh the implications of proceeding beyond five cycles and to engage patients in discussions regarding individualized treatment strategies.

- -Need for Further Research-: The study recognizes potential biases, including selection and information biases, characteristic of retrospective designs. It calls for further large-scale, prospective research to comprehensively investigate the long-term effects of repeated COS on fertility and to inform clinical guidelines effectively.

Reference –

Shiming Wang et al. (2025). Effect Of Repeated Controlled Ovarian Stimulation On Pregnancy Outcomes In Fresh Embryo Transfer Cycles: A Retrospective Cohort Study. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07613-0.