Assessing the impact of the number of letrozole-stimulated follicles on multiple gestation rates in patients undergoing intrauterine insemination

Abstract Study Question: Limits on the number of stimulated follicles (SF) after ovarian stimulation (OS), to minimize the multiple gestation rate (MGR), has public health importance. Studies have focused on gonadotropins or clomiphene citrate. We aimed to assess the relationship between letrozole-stimulated follicles (SF) before IUI and the MGR. Design: We completed a retrospective cohort study of 418 cycles at an academic centre. Women undergoing OS with letrozole plus IUI were included. Statistical analysis was completed with correlation coefficients and multivariate logistic regression analysis. Results: The clinical pregnancy rate (CPR) was 10.5%, whereas MGR was 1% per cycle start, and 9% of pregnancies. The number of SF ≥ 10mm, SF ≥ 14mm or SF ≥ 16mm at trigger were assessed for a relationship to CPR. No statistical relationship was seen. The number of SF ≥ 10mm was unrelated to CPR (r= -0.04, p = 0.40), fetal sacs (FS) (r=-0.32, p = 0.51) and fetal heartbeats (FHB) (r=-0.17, p = 0.73). For SF ≥ 14mm the results for CPR, FS, and FHB were (r=-0.009, p = 0.86), (r=-0.003, p = 0.94) and (r = 0.007, p = 0.88) respectively. Non-significance was seen with SF ≥ 16mm CP (r = 0.036, p = 0.47), FS (r = 0.037, p = 0.45) and FHB (r = 0.054, p = 0.27). Multivariate logistic regression revealed no cases where the number of SF ≥ 10mm, ≥ 14mm, or ≥ 16mm, were predictors of CP when controlling for age, diagnosis, prior IUI or semen parameters. Conclusions: We did not show an association between the number of SF, up to 3, and the number of FS or FHB. Letrozole-stimulated females with up to 3 SF before IUI do not require cancellation. What does this study add to the clinical work? We have been able to reaffirm the safety of using letrozole for IUI up to the presence of 3 dominant follicles. Further research is required to determine the multiple gestation rate associated with 4 or more dominant follicles.