THE SAFETY AND EFFECTIVENESS OF MILD GONADOTROPIN STIMULATION/INTRAUTERINE INSEMINATION IN IDIOPATHIC INFERTILITY. DO SHOTS WORK BETTER THAN PILLS?

Abstract

Ovulation induction (OI) with gonadotropins (Gn) has been associated with higher overall success than oral medication (oral med), albeit higher rate of multiples. Our objective was to compare the success and safety of a mild Gn stimulation/IUI regimen to oral med [clomiphene citrate (CC) or letrozole]/IUI regimen among patients with idiopathic infertility (IdI). Retrospective cohort study. Setting: Academic fertility center. Patients: Women with IdI undergoing OI/IUI from 12/2003 - 09/2019. Interventions: Retrospectively reviewed data from 3,155 OI/IUI cycles (1,193 patients). Gn/IUI cycles (n=2,113) were compared to oral med/IUI ones (n =1,042). Outcomes: Primary: Clinical pregnancy rate (CPR)/cycle. Secondary: Spontaneous abortion, non-viable pregnancy (ectopic, biochemical, unknown location), and multiple pregnancy rates (SABR, NVPR, and MPR, respectively), and cycle characteristics: length of stimulation (days), pre-ovulatory follicle number (≥ 13 mm), endometrial thickness (ET), and cycle cancellation due to over-response. Statistics: Wilcoxon rank sum, x2-tests, and logistic regression were used. Odds ratios (OR) were calculated utilizing generalized linear mixed effects models, adjusted for age and multiple cycles per patient. Gn/IUI patients compared to oral med/IUI patients were older, had higher FSH and lower AMH levels [mean (SD): 35.2 (3.6) vs. 33.5 (3.3) years, p<0.001; 7.1 (2.1) vs. 6.9 (1.8) IU/mL, p: 0.005; 3.0 (2.1) vs. 3.5 (2.4) ng/mL, p<0.001; respectively]. Mean (SD) daily FSH dose was 58.9 (45) IU producing a mean (SD): 2.2 (1.4) follicles in the Gn/IUI group. When comparing Gn/IUI to oral med/IUI cycles, CPR was significantly higher in the former group (CPR: 14.5% vs 11.7%, p: 0.03, respectively), which had higher odds of clinical pregnancy [OR (95%CI): 1.28 (1.0, 1.6), p: 0.03; aOR (95%CI): 1.32 (1.0, 1.7), p: 0.036]. Results did not change when restricting the comparison of Gn/IUI to CC/IUI cycles only [14.5% vs 11.6%, p: 0.026; aOR (95%CI): 1.29 (1.0, 1.6), p: 0.03, respectively]. Gn/IUI compared to oral med/IUI cycles, had significantly shorter stimulation duration, lower cancellation risk, and thicker endometrium [mean (SD): 10.6 (2.2) vs 12.0 (1.8) days, p<0.001; 3.6% vs 6.0%, p: 0.003; 8.6 (2.1) vs 7.2 (2.1) mm, p<0.001; respectively). Mean number of follicles differed between groups but not in a clinically meaningful way [mean (SD): 2.2 (1.4) vs. 2.0 (1.5), p: 0.001, Gn/IUI vs oral med/IUI). Age-adjusted MPR and SAB rate did not differ between groups [MPR: 12.5% vs 11.5%, p: 0.82, aOR (95%CI): 0.8 (0.4, 1.9, p: 0.63; SAB: 20.8% vs 10.7%, p: 0.013, aOR (95%CI): 1.7 (0.9, 3.4), p: 0.11, Gn/IUI vs oral med/IUI]. NVPR was lower for Gn/IUI cycles [8.8% vs 15.1%, p: 0.042, aOR (95%CI): 0.47 (0.3, 0.9), p: 0.02, respectively]. Our data suggests that among IdI patients, mild stimulation with Gn is associated with a significantly higher CPR and a lower NVPR, without an increased risk of a multiple pregnancy. Mild stimulation with gonadotropins coupled with IUI is a safe and effective treatment of IdI.