Association between duration of controlled ovarian stimulation and live birth rate in women undergoing In Vitro Fertilization: a SART CORS analysis

Abstract

Background: In-Vitro Fertilization (IVF) treatment involves synchronization of multiple time-sensitive events, most of which are rate-limiting too. Controlled ovarian stimulation (COS) is one such event. The reproductive outcomes based on the duration of COS (d-COS) in a fresh, IVF embryo transfer (ET) are not well established and therefore, remains largely uncertain. Objective: To evaluate the association between d-COS and live birth rate (LBR) in women undergoing a fresh IVF-ET using autologous oocytes. Methods: A retrospective cohort study was conducted using a US nationwide IVF register – SARTCORS (Society for Assisted Reproductive Technology Clinic Outcomes Reporting System). From a total of 93,889 cycles, we included 56,666 fresh, autologous, IVF - ET treatment cycles from January 2014 through December 2015, with follow-up until October 2016. Adjusted odds and risk ratio with 95% confidence intervals were estimated while controlling for multiple demographic factors and other potential confounders. Variables and outcomes: The primary exposure variable was d-COS defined as the difference in days between gonadotrophin administration and oocyte retrieval. The primary outcome measure was live birth following a fresh IVF-ET. Secondary outcome measures included biochemical pregnancy rate, miscarriage rate, implantation rate and clinical pregnancy rate. Results: A total of 56,666 treatment cycles (mean [SD] age of 33.9 [4.47], BMI of 26.1 [6.02], AMH value of 2.19 [3.37]), and a baseline FSH value of 7.62 [3.49]) underwent a fresh IVF-ET. The LBR after a combined analysis for all ages and all protocols was 44.2 % (n = 25043). In the combined analysis, there was a statistically significant decrease in the live birth rate with LBR with d-COS beyond 10 days. The adjusted OR (95% CI) of LBR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to optimal duration of 10 days was 0.97 (0.87-0.99), 0.94 (0.8-1), 0.83 (0.77-0.89) and 0.73 (0.68-0.79) respectively. The AOR (95% CI) of miscarriage rates for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 1.12 (1-1.26), 0.99 (0.87-1.12), 1.03 (0.90 -1.17) and 1.04 (0.90 - 1.2) respectively. With increasing d-COS, the implantation rate (IR) and clinical pregnancy rate (CPR) also showed a decreasing trend, as with other reproductive outcomes. The RR (95% CI) for implantation rate in a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.97 (0.93-1), 0.97 (0.93-1.01), 0.91 (0.87-0.95) and 0.86 (0.82-0.9). The adjusted OR (95% CI) of CPR for a woman who had 11, 12, 13 and ≥14 days of COS, compared to referent was 0.95 (0.89-1.01), 0.93 (0.87-0.99), 0.8 (0.75-0.86) and 0.7 (0.65-0.75) respectively. Conclusions and Relevance: In this nationwide cohort study of women undergoing fresh IVF-ET using autologous oocytes, controlled ovarian stimulation lasting approximately 10-days was associated with an optimal live birth rate.