The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drug-dosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292325, identifier CRD42021292325.