Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers

Abstract Background Fertility 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,...

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Main Authors: Oranite Goldrat, Geraldine Van Den Steen, Eric Gonzalez-Merino, Julie Dechène, Christine Gervy, Anne Delbaere, Fabienne Devreker, Viviane De Maertelaer, Isabelle Demeestere
Format: Article
Language:English
Published: BMC 2019-01-01
Series:Reproductive Biology and Endocrinology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12958-018-0443-x
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author Oranite Goldrat
Geraldine Van Den Steen
Eric Gonzalez-Merino
Julie Dechène
Christine Gervy
Anne Delbaere
Fabienne Devreker
Viviane De Maertelaer
Isabelle Demeestere
author_facet Oranite Goldrat
Geraldine Van Den Steen
Eric Gonzalez-Merino
Julie Dechène
Christine Gervy
Anne Delbaere
Fabienne Devreker
Viviane De Maertelaer
Isabelle Demeestere
author_sort Oranite Goldrat
collection DOAJ
description Abstract Background Fertility 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. Methods In 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. Results FF 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. Conclusions Let-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 registration Clinicaltrials.gov -NCT02661932, registered 25 January 2016, retrospectively registered.
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spelling doaj.art-e7b796bf57ca41369eb54b9aae89e6de2022-12-21T20:32:37ZengBMCReproductive Biology and Endocrinology1477-78272019-01-011711910.1186/s12958-018-0443-xLetrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkersOranite Goldrat0Geraldine Van Den Steen1Eric Gonzalez-Merino2Julie Dechène3Christine Gervy4Anne Delbaere5Fabienne Devreker6Viviane De Maertelaer7Isabelle Demeestere8Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)Research Laboratory on Human Reproduction, Université Libre de Bruxelles (ULB)Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)Research Laboratory on Human Reproduction, Université Libre de Bruxelles (ULB)Laboratory of Chemistry, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)IRIBHM and SBIM, Université Libre de Bruxelles (ULB)Fertility Clinic, Department of Obstetrics and Gynecology, CUB-Hôpital Erasme, Université Libre de Bruxelles (ULB)Abstract Background Fertility 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. Methods In 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. Results FF 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. Conclusions Let-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 registration Clinicaltrials.gov -NCT02661932, registered 25 January 2016, retrospectively registered.http://link.springer.com/article/10.1186/s12958-018-0443-xBreast cancerControlled ovarian hyperstimulationLetrozoleOocyte qualityFollicular fluidCumulus cells
spellingShingle Oranite Goldrat
Geraldine Van Den Steen
Eric Gonzalez-Merino
Julie Dechène
Christine Gervy
Anne Delbaere
Fabienne Devreker
Viviane De Maertelaer
Isabelle Demeestere
Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
Reproductive Biology and Endocrinology
Breast cancer
Controlled ovarian hyperstimulation
Letrozole
Oocyte quality
Follicular fluid
Cumulus cells
title Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
title_full Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
title_fullStr Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
title_full_unstemmed Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
title_short Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers
title_sort letrozole associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients assessment of oocyte quality related biomarkers
topic Breast cancer
Controlled ovarian hyperstimulation
Letrozole
Oocyte quality
Follicular fluid
Cumulus cells
url http://link.springer.com/article/10.1186/s12958-018-0443-x
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