Ovulation triggers in unassisted reproduction, an old question still unanswered: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether ovulation triggers improve pregnancy and/or ovulation rates in women with unexplained or anovulatory infertility undergoing ovulation induction and natural intercourse or intrauterine insemination (IUI), without increasing complications. METHODS: We searched nine databases and grey literature from inception to August 29, 2023. Parallel-group randomized controlled trials (RCTs) including women with unexplained or anovulatory infertility undergoing ovulation induction and natural intercourse or IUI, comparing ovulation trigger versus placebo or no treatment, were included. Outcomes included pregnancy, ovulation, and complications. Risk of bias was assessed using the RoB 2 tool, and GRADE was applied for certainty of evidence. The Hartung-Knapp random-effects model was used to calculate odds ratio (ORs) (α=0.05). R packages "metafor", "meta", and "metasens" were used. RESULTS: Six studies (1,218 women) were included; all studies used hCG as the trigger. For clinical pregnancy (n=855, 4 studies), OR=1.23 (95% CI: 0.91-1.66); for live birth (n=45, 2 studies), OR=0.92 (95% CI: 0.14-6.02); for miscarriage (n=89, 3 studies), OR=0.68 (95% CI: 0.20-2.35); for ovulation (n=311, 2 studies), OR=1.70 (95% CI: 0.84-3.43); and for multiple pregnancy (n=523, 2 studies), OR=2.56 (95% CI: 0.43-15.11). No subgroup analysis altered certainty of evidence and risk of bias was low. CONCLUSIONS: Current evidence is insufficient to recommend or refute ovulation triggers. hCG may increase ovulation, but effects on pregnancy outcomes remain uncertain.