Follicular Phase Endocrine Characteristics during Ovarian Stimulation and GnRH Antagonist Cotreatment for IVF: RCT Comparing recFSH Initiated on Cycle Day 2 or 5

Abstract

Abstract Context: Strategies involving mild ovarian stimulation protocols for in vitro fertilization (IVF) might lessen discomfort to the patient and substantially lower complication rates. Objective: The objective of the study was to compare the follicular-phase endocrine characteristics and follicular development in patients who started recombinant FSH (recFSH) on cycle day (CD) 2 or CD5 in IVF treatment, using GnRH antagonist as comedication. Design: This was a prospective randomized controlled trial in two university centers in Belgium and The Netherlands. Patients: Seventy-six IVF/intracytoplasmic sperm injection patients were included in the study. Interventions: The control group (CD2) received a standard treatment with 150 IU recFSH from CD2, whereas in the study group (CD5), stimulation was started on d 5 of the cycle. The GnRH antagonist was administered daily from CD6 onward in both treatment arms. Main Outcome Measure: Endocrine follicular phase profile during ovarian stimulation was measured. Results: Follicular-phase patterns of gonadotropin and steroid concentrations were found to be comparable in both treatment groups, except for serum estradiol being significantly higher in the CD2 group on d 6 of the cycle (295.6 ± 202.5 ng/liter in the CD2 vs. 102.5 ± 47.9 ng/liter in the CD5 group; P < 0.01) and LH being significantly higher in the CD5 group on d 6 of the cycle (1.7 ± 0.7 IU/liter in the CD2 vs. 5.0 ± 2.1 IU/liter in the CD5 group; P < 0.01). With regard to follicular development, there was no difference in the numbers of small follicles (<10 mm), intermediate follicles (10–12 and > 12–14 mm) and large follicles (>14 mm) in both groups. Conclusions: This study shows that the administration of recFSH starting on d 2 or d 5 of the cycle in a GnRH antagonist protocol for IVF/intracytoplasmic sperm injection patients yields a comparable endocrine profile and follicular development. Future studies should focus on the design of more patient-tailored ovarian stimulation protocols.