Continuous Combined Letrozole-FSH Stimulation Requires Less FSH With Similar Outcomes Compared To Standard Ovarian Stimulation Regimens for IVF

Abstract

We have previously described a combined letrozole-FSH stimulation protocol (letFSH) for breast cancer patients undergoing IVF for embryo cryopreservation. Our current objective was to compare this protocol to standard IVF protocols. Prospective study with age matched controls. Twenty-five breast cancer patients were treated by letFSH protocol in which letrozole 5 mg was started on cycle day 2 and FSH 150 IU was added on cycle day 4. Both medications continued until the day of hCG. GnRH antagonist was administered when E2>250pg/mL. Standard protocol group consisted of leuprolide suppression followed by gonadotropins (n=68) or gonadotropins with GnRH antagonists (n=27). Day-3 FSH levels were similar between the letFSH and the age-matched standard IVF protocol patients (table). Despite the significantly lower peak estradiol levels in the letFSH group, endometrial thickness, percent mature oocytes, fertilization rates and number of 2-pronuclei embryos were similar to standard-IVF patients (table). However, hCG had to be administered at a significantly larger follicle diameter to achieve these results. The loess fit analysis showed that an average diameter of approximately 20 mm of the two leading follicles resulted in the best fertilization rates with letFSH. The length of stimulation was not different between letFSH and standard IVF stimulation cycles (table). While letFSH resulted in higher number of ≥17 follicles, 46 % less FSH was required to achieve these results compared to all standard-IVF cycles. When this was compared to the results of the stimulation with gonadotropins+GnRH antagonist, a protocol more comparable to the stimulation in letFSH, the FSH requirement was reduced further by 65%. Tabled 1 Continuous administration of letrozole with FSH results in similar fertilization rates, number of two pronuclear embryos per cycle, and endometrial thickness while significantly reducing the requirement for gonadotropin administration compared to standard ovarian stimulation protocols. The hCG administration criteria has to be modified but since length of stimulation with letFSH is similar to that of with standard IVF, this is likely to be due to altered antral fluid dynamics. In addition to its use for embryo cryopreservation in breast cancer patients prior to chemotherapy, this combined continous letrozole-FSH protocol may be a cost saving alternative to standard ovarian stimulation protocols.