Comparison of stimulation protocols for dose determination of gonadotropins: A systematic review and Bayesian network meta‐analysis based on randomized controlled trials

Abstract

BackgroundTo date, evidence regarding the effectiveness and safety of individualized controlled ovarian stimulation (COS) compared with standard dose COS has been inadequate.ObjectivesTo evaluate the updated evidence from published randomized controlled trials (RCTs) about the efficacy and safety of individualized COS with different ovarian reserve test biomarkers or clinical experience versus standard dose COS.Search StrategyTerms and descriptors related to COS, individualized or standard, and RCT were combined to search, and only English language studies were included. Conference abstracts and comments were excluded.Selection CriteriaRCTs with comparison between different individualized COS strategies and standard starting dose strategy were included.Data Collection and AnalysisTwo reviews independently assessed the eligibility of retrieved citations in a predefined standardized manner. Relative risk (RRs) and the weighted mean difference (WMD) with 95% confidence intervals (CIs) were pooled using a random‐effects model on R software version 4.2.2.Main ResultsCompared with the standard dose COS strategy in pairwise meta‐analysis, the individualized COS strategy was associated with a notable lower risk of ovarian hyperstimulation syndrome (OHSS; 174/2384 [7.30%] vs 114/2412 [4.73%], RR 0.66, 95% CI: 0.47–0.93, I2 = 46%), a significantly lower risk of hyperresponse to stimulation (hyperresponse; 476/2402 [19.82%] vs 331/2437 [13.58%], RR 0.71, 95% CI: 0.57–0.90, I2 = 61%), and a slightly longer ovarian stimulation days (duration of stimulation; WMD 0.20, 95% CI: 0.01–0.40, I2 = 66%). Bayesian network meta‐analysis also found that biomarker‐tailored strategy had a significantly lower risk of OHSS than standard dose strategy (OHSS; RR 0.63, 95% CI: 0.41–0.97, I2 = 47.5%).ConclusionCompared with standard dose COS strategy, individualized COS strategy could significantly reduce the risks of OHSS and hyperresponse to stimulation, but the duration of stimulation was slightly longer.Trial RegistrationPROSPERO: CRD42023358439.