Early versus late follicular phase ovarian stimulation: a randomized controlled trial

Research question Is late follicular phase stimulation equally efficient as early follicular phase stimulation in a GnRH antagonist protocol in oocyte donors in terms of number of oocytes? Design In this open label, phase 3, non-inferiority, RCT using a two-arm design with 1:1 allocation ratio, 84 oocyte donors were allocated to early follicular start (control group, n=41), or late follicular start (study group, n=43). In the control group, patients followed a fixed GnRH antagonist protocol with r-FSH 225IU. In the study group, r-FSH 225IU was initiated in the late follicular phase. Primary outcome was number of oocytes. Secondary endpoints included number of mature oocytes, consumption of gonadotropins and GnRH antagonist, and stimulation cost. Results Number of oocytes did not differ between control group and study group (intention-to-treat analysis 15.5±11.0 vs 14.0±10.7, p=0.52, per-protocol analysis 18.2±9.7 vs 18.8±7.8, p=0.62). Number of mature oocytes did not differ (14.1±8.1 vs 12.7±8.5, p=0.48). Duration of stimulation was shorter in the control group (10.0±1.6 vs 10.9±1.5 days, p=0.01). Total amount of r-FSH used was lower in the control group (2240.7±313.9 IU vs 2453.9±330.1 IU p=0.008). A GnRH antagonist was used for approximately 6 days in the control group, while in the study group, only in one patient a GnRH antagonist was prescribed (6.0±1.4 days vs 0.13±0.7 days p<0.001). There was a significant difference in medication cost per cycle (1147.9±182.8€ in control group, vs 979.9±129.0€ in study group, p<0.001). Conclusions Late follicular phase stimulation is as efficient as early follicular phase stimulation in terms of number of oocytes.