Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor
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(2020) 13:66
RESEARCH
Open Access
Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders? Moran Shapira, Raoul Orvieto, Oshrit Lebovitz, Ravit Nahum, Adva Aizer, Aliza Segev-Zahav and Jigal Haas*
Abstract Background: Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course. Methods: We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed. Results: Twenty-four patients were included. Mean patients’ age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%. Conclusion: Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders. Keywords: Letrozole, Aromatase inhibitors, Poor responders, Androgens, IVF
Background The role of androgens in female reproduction has been extensively studied in the past two decades. It is now clear that androgens, although traditionally thought to be male sex steroids, are significantly involved in regulating normal and pathological female reproductive states. Androgens serve as a substrate for estradiol production, promote the * Correspondence: [email protected] IVF unit, Division of Obstetrics and Gynecology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv Israel
proliferation of granulosa and theca cells, stimulate the growth of small follicles and increase FSH receptor gene expression as well as IGF-I and IGF-I receptors [1–3] . This knowledge has prompted the incorporation of androgens and androgen-modulating agents into the clinical practice of assisted reproduction technologies (ART). One such androgen modulating agent is Letrozole, a selective, non-steroidal aromatase inhibitor. It competitively binds to the heme of the cytochrome P450 subunit of the aromatase enzyme, thereby blocking the conversion of
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