O Goldrat1, C Gervy2, Y Englert3, A Delbaere3, I Demeestere3. 1. Fertility Clinic, Department of Obstetrics and Gynecology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium oranite.goldrat@erasme.ulb.ac.be. 2. Laboratory of Chemistry, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 3. Fertility Clinic, Department of Obstetrics and Gynecology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium.
Abstract
STUDY QUESTION: Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancer patients, lower than after standard in vitro fertilization (IVF) cycles? SUMMARY ANSWER: During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. WHAT IS KNOWN ALREADY: Current fertility preservation strategies for breast cancer patients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. STUDY DESIGN, SIZE, DURATION: This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancer patients undergoing letrozole-associated COS with 21 infertile patients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertility patients. MAIN RESULTS AND THE ROLE OF CHANCE: While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. LIMITATIONS, REASONS FOR CAUTION: The studied populations (breast cancer and infertile patients) are different, which may induce selection bias. The small sample size limits the study's statistical power and the possibility to perform multivariate analysis. Recruitment of the study and control patients was completed at the same time; however, enrollment of controls started at a later time. WIDER IMPLICATIONS OF THE FINDINGS: While the use of letrozole in fertility preservation patients has a favorable effect on estrogen levels, no benefit is seen for progesterone levels which are high and comparable with progesterone levels after standard COS in IVF patients. As progesterone has been associated with tumor cell proliferation, caution is mandatory. Modified protocols including GnRH agonist triggering should be investigated.
STUDY QUESTION: Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancerpatients, lower than after standard in vitro fertilization (IVF) cycles? SUMMARY ANSWER: During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. WHAT IS KNOWN ALREADY: Current fertility preservation strategies for breast cancerpatients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. STUDY DESIGN, SIZE, DURATION: This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancerpatients undergoing letrozole-associated COS with 21 infertilepatients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertilitypatients. MAIN RESULTS AND THE ROLE OF CHANCE: While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. LIMITATIONS, REASONS FOR CAUTION: The studied populations (breast cancer and infertilepatients) are different, which may induce selection bias. The small sample size limits the study's statistical power and the possibility to perform multivariate analysis. Recruitment of the study and control patients was completed at the same time; however, enrollment of controls started at a later time. WIDER IMPLICATIONS OF THE FINDINGS: While the use of letrozole in fertility preservation patients has a favorable effect on estrogen levels, no benefit is seen for progesterone levels which are high and comparable with progesterone levels after standard COS in IVFpatients. As progesterone has been associated with tumor cell proliferation, caution is mandatory. Modified protocols including GnRH agonist triggering should be investigated.
Authors: Molly B Moravek; Rafael Confino; Angela K Lawson; Kristin N Smith; Ralph R Kazer; Susan C Klock; William J Gradishar; Jacqueline S Jeruss; Mary Ellen Pavone Journal: Breast Cancer Res Treat Date: 2021-01-04 Impact factor: 4.872