Determining the optimal follicle size at trigger in patients undergoing ovarian stimulation with a clomiphene citrate plus gonadotropin and GnRH antagonist protocol for in-vitro fertilization.

Abstract

The aim of this paper was to determine the optimal follicle size at trigger in clomiphene citrate-based in vitro fertilization (IVF) protocols. This is a retrospective cohort study performed in at a single academic institution that included first IVF cycles with clomiphene citrate-based protocols at our center between 01/01/2013 and 03/31/2019. Patients were dichotomized by whether they had ≥2 follicles >20 mm on trigger day. Group A consisted of patients with <2 follicles >20 mm on trigger day and Group B consisted of patients with ≥2 follicles >20 mm on trigger day. The primary outcome was the number of mature oocytes retrieved. Secondary outcomes included pregnancy and live birth rates. A total of 635 patients were included: (Group A=399 patients and Group B=236 patients). The median (IQR) diameter of the largest follicle was 20.0 mm (19.0-21.0) in Group A and 22.7 mm (21.8-24.0) in Group B (P<0.001). Among the entire cohort, mean number of oocytes retrieved was significantly higher in Group B (9.9±6.5; RR 1.08 [95% CI 1.03-1.14]) compared to Group A (9.2±6.3). In a subgroup analysis of patients in the upper quartile for age (≥41.7 years), Group B had significantly more oocytes retrieved (8.1±5.9 vs. 6.7±4.5; RR 1.23 (95% CI 1.10-1.38]), more mature oocytes retrieved (6.0±4.0 vs. 5.2±3.4; RR 1.16 [95% CI 1.02-1.33]), and more zygotes (4.7±3.5 vs. 3.6±2.8; RR 1.32 [95% CI 1.13-1.55]). In the secondary analysis, pregnancy and live birth rates after fresh transfer were similar between groups. In clomiphene citrate-based IVF protocols, administering the ovulatory trigger at larger follicle sizes yielded more total oocytes retrieved without a significant difference in mature oocyte number. In older patients, larger follicle sizes at trigger yielded more mature oocytes and zygotes per retrieval. Based on these results, in older patients it may be advantageous to administer the ovulatory trigger in clomiphene-based IVF cycles when two or more follicles measures >20 mm. However, this benefit was not observed when assessed among all ages combined.