Abstract
BackgroundFertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality.MethodsIn this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups.ResultsFF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4–438) vs 64.4 (43.8–152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5–466.7) vs 354 (179–511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa.ConclusionsLet-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients.Trial registrationClinicaltrials.gov -NCT02661932, registered 25 January 2016, retrospectively registered.
Highlights
Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH)
High estradiol level observed during controlled ovarian hyperstimulation (COH) before oocyte collection has been subject of debate regarding possible proliferative effects on the tumor
Biomarkers data were analyzed separately for Human chorionic gonadotropin (hCG) and GnRHa triggers, as follicular microenvironment differs according to ovulation trigger method [28,29,30]
Summary
Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). The impact of Let-COH on the follicular microenvironment has been poorly investigated, a high androgen/estrogen ratio was previously associated with low oocyte quality. More than a decade ago, a new COH protocol associated with letrozole, a type II nonsteroidal competitive aromatase inhibitor, was developed (Let-COH) to collect several mature oocytes while potentially avoiding negative effects of estrogens on tumor growth [9, 10]. Through its competitive action on the aromatase enzyme [11, 12], letrozole prevents the aromatization of androgens to estrogens, which may induce significant changes in the endocrine follicular environment and impact oocyte competence. Recent studies have shown significantly improved oocyte yield in BC patients undergoing Let-COH for FP compared to conventional COH for elective oocyte cryopreservation, as well as in infertile patients undergoing IVF with Let-COH or conventional COH [18, 19]
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