Ovarian stimulation and intrauterine insemination at the quarter centennial: implications for the multiple births epidemic

Ovarian stimulation and intrauterine insemination (OS/IUI), a mainstay of current infertility therapy and a common antecedent to IVF, is a significant driver of the multiple births epidemic. Redress of this challenge, now marking its quarter centennial, will require a rethinking of current practice patterns. Herein we explore prospects for prevention, mitigation, and eventual resolution. We conclude that the multiple births attributable to OS/IUI may not be entirely preventable but that the outlook for their mitigation is promising, if in need of solidification. Specifically, we observe that low-dose (≤75 IU) gondotropin, clomiphene, and especially off-label letrozole regimens outperform high-dose (≥150 IU) gonadotropin counterparts in the gestational plurality category while maintaining comparable per-cycle pregnancy rates. Accordingly we recommend that, subject to appropriate exceptions, high-dose gonadotropin regimens be used sparingly and that whenever possible they be replaced with emerging alternatives. Finally, we posit that OS/IUI is not likely to be superseded by IVF absent further commoditization and thus greater affordability.