Gonadotropins versus oral ovarian stimulation agents for unexplained infertility: a systematic review and meta-analysis.

OBJECTIVE:To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins. DESIGN:Systemic review and meta-analysis. SETTING:Not applicable. PATIENT(S):Patients undergoing OS-IUI for treatment of unexplained infertility. INTERVENTION(S):Clomiphene, letrozole, or gonadotropins for OS-IUI. MAIN OUTCOME MEASURE(S):Live birth and multiple gestation. RESULT(S):Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses. CONCLUSION(S):For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility. CLINICAL TRIAL REGISTRATION NUMBER:Prospero CRD4201911998.