The best ovarian reserve marker to predict ovarian response following controlled ovarian hyperstimulation: a systematic review and meta-analysis

Background: One of the most challenging aspects of treating patients facing primary ovarian insufficiency, especially those eligible for controlled ovarian hyperstimulation (COH), is the assessment of ovarian function and response to stimulatory protocols in terms of the number of oocytes retrieved. The lack of consistency between studies regarding the best parameter for response evaluation necessitates a comprehensive statistical analysis of the most commonly utilized ovarian reserve markers (ORM). This systematic review and meta-analysis aims to establish the optimal metric for assessing ovarian reserve among COH candidates.

Methods: The PubMed/MEDLINE, Scopus, and ISI Web of Science databases were searched until July 2024, with no date or language limitations. The Newcastle-Ottawa scale was used to evaluate the validity of anti-Mullerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), and estradiol (E2) in patients receiving controlled ovarian hyperstimulation. Studies on the diagnostic accuracy of ovarian reserve markers in predicting ovarian response to controlled ovarian hyperstimulation in assisted reproduction technology (ART) candidates were reviewed. The diagnostic odds ratio (DOR) was determined using the Der Simonian-Laird random effects model meta-analysis to assess the likelihood of detecting low or high ovarian responses in COH candidates. Cochran's Q, and I-squared, were used to analyze between-study heterogeneity.

Results: This systematic review and meta-analysis included 26 studies including 17 cohorts, 4 case controls, and 5 cross-sectional studies. AFC and AMH demonstrated significant diagnostic performance compared to FSH and E2 in poor and high response category. AMH slightly outperformed AMH and had the highest logarithm of DOR for detecting poor [2.68 (95% CI 1.90, 3.45)] and high ovarian response [2.76 (95% CI 1.57, 3.95)]. However, it showed a high between-study heterogeneity (I² = 95.65, Q = 189.65, p < 0.05).

Conclusions: AFC and AMH were the most accurate predictors of poor and high ovarian response to controlled ovarian hyperstimulation. However, further research is needed to develop models assessing the combined impact of AMH and AFC on ovarian response prediction.

Systematic review registration: PROSPERO CRD42021245380.