Does Daily Co-Administration of Gonadotropins and Letrozole during the Ovarian Stimulation Improve IVF Outcome for Normal, Poor, and Sub-Optimal Responders?

Abstract – Objectives: Address and identify the sub-group of patients that might benefit from letrozole co-treatment throughout the entire ovarian stimulation (OS). Design: A retrospective cohort study. Patients: Patients who underwent two successive IVF cycle attempts, where the 2nd included the co-administration of 5 mg Letrozole from OS day 1 until trigger day. Setting: IVF institute of a tertiary medical center. Methods: First and second cycle attemtps were compared with regard to cycle characteristics and results. Different subroups according to ovarian response were considered. Results: Two hundred patients met the inclusion criteria and were included in the study. Of whom, 65 were poor responders (oocytes ≤3) during the first IVF cycle attempt, 85 were sub-optimal responders (4–9 oocytes), and 50 were normal responders (≥10 oocytes). The total dose of gonadotropins (4, 525 ± 1, 553 vs. 4, 293 ± 2, 166, p = NS) and length of stimulation (11.3 ± 2.2 vs. 11.1 ± 2.3, p = NS) were comparable between the two cycle attempts. Numbers of follicles ≥13 mm (7.2 ± 4.7 vs. 6.2 ± 4.3, p < 0.001), retrieved oocytes (8.6 ± 6.1 vs. 6.9 ± 5.5, p < 0.001), zygotes (5.7 ± 4.5 vs. 4.5 ± 3.7, p < 0.001) and number of top quality embryos (TQE) (2.5 ± 2.5 vs. 1.8 ± 1.9, p < 0.001) were significantly higher in letrozole cycles. Sub-analysis according to patients’ ovarian response during the first attempt revealed that the poor and sub-optimal responders significantly benefit from the letrozole co-administration, while the normal responders did not. Conclusions: Letrozole co-administration during OS for IVF increases the number of retrieved oocytes, zygotes, and TQE in poor and sub-optimal responders but not in normal responders.