ART outcomes following ovarian stimulation in the luteal phase:a systematic review and meta-analysis

Purpose: This study aimed to evaluate the impact of luteal phase ovarian stimulation (LPS) on the outcomes of assisted reproductive technology (ART) for infertile couples and patients desiring non-urgent egg cryopreservation. Methods: We included all studies reported patients who received LPS and that used follicular phase ovarian stimulation (FPS) as a comparison group until January 2021. Prior meta-analysis regarding the outcomes of LPS in double stimulation and fertility preservation have already been published, so these studies were excluded. Risk of Bias in Non-randomized Studies of Interventions was used to assess the study quality. The study was registered in the International Prospective Register of Systematic Reviews database (CRD42020183946). Results: Twelve studies with a total of 4433 patients were included. The regimen employed can be categorized into two groups, but there is currently no evidence to support one over the other. After we excluded the largest study, the clinical pregnancy rate and live birth rate were similar after FPS and LPS. There were significantly more stimulation days and total gonadotropins used in the LPS group. After subgroup analysis, we found that poor responders received significantly more cumulus oocyte complexes (+0.64) in the LPS group. Conclusion: Current evidence indicates that patients in the LPS group could achieve pregnancy outcomes non-inferior to those in the FPS group. Because of current debate over freeze-all policy and the limited data about live birth rate, the universal use of LPS is considered controversial. In the future, more well-designed studies are necessary to investigate the indications for LPS and its cost-effectiveness.