A comparison of oral versus injectable ovarian stimulation in IUI in women ≥38 years of age with decreased ovarian reserve

Purpose To compare pregnancy rates of oral ovarian hyperstimulation agents (clomiphene citrate (CC) and letrozole) versus injectable agents (gonadotropins) in intrauterine insemination (IUI) in the older reproductive age group with diminished ovarian reserve. Methods A retrospective cohort study was performed among 210 women 38-43 years of age undergoing IUI with controlled ovarian hyperstimulation (COH) at a single academic institution between 2009 and 2018. Results A total of 335 IUI cycles met inclusion criteria. Gonadotropins were the most frequently used ovarian hyperstimulation agent (n = 264), followed by CC (n = 38) and letrozole (n = 33). Mean age of the cohort was 40.5 (+/- 1.6) years (range 38-43) did not differ significantly among groups (p = 0.41). Mean AFC and number of mature follicles on day of ovulation trigger also did not differ among groups (p = 0.98, p = 0.10). Overall clinical pregnancy rate was 7.5% per cycle, and rates for CC, letrozole, and gonadotropins respectively were 5.3%, 9.1%, 7.5% per cycle (p = 0.347). There was one multiple gestation pregnancy (twins), which was in a patient stimulated with gonadotropins. Conclusion This is the first study to compare CC, letrozole, and gonadotropins in older reproductive age women with decreased ovarian reserve. The findings reveal that COH/IUI in older women with decreased ovarian reserve is a viable option (clinical pregnancy rate of 7.5% per cycle), and suggest that oral stimulation agents may be the first-line option, with letrozole having conferred the highest clinical pregnancy rate, 9.1%, which is notable given the typical poor fecundability of this population. However, larger population studies are needed to support this.