Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression

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This study compared outcomes of medical or surgical treatment versus no treatment before embryo transfer in women with abnormal endometrial BCL6 expression and suspected endometriosis.

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This prospective cohort study in a university infertility clinic evaluated whether medical suppression with a GnRH agonist (depot leuprolide for 2 months) or diagnostic/therapeutic laparoscopy prior to embryo transfer improves outcomes in women with elevated endometrial BCL6 expression (HSCORE ≥1.4) and suspected endometriosis, compared with no pre-treatment. After biopsy and BCL6 immunostaining, implantation rate, clinical pregnancy rate, live birth rate, cycle characteristics, and miscarriage rate were compared between treated groups (including laparoscopy or medical suppression) and untreated controls, with groups reported as similar in baseline characteristics. Treated women had substantially higher live birth rates (50% for medical suppression and 52.4% for laparoscopy) than controls (7.4%), alongside more miscarriages in the control group. This paper is centrally about endometriosis — it assesses suspected endometriosis-related aberrant endometrial BCL6 expression and compares pre-embryo-transfer medical or surgical treatment effects on reproductive outcomes.

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Abstract

PurposeTo evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic.MethodsAll subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group.ResultsWomen in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group.ConclusionsWomen with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management.
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Abstract

Purpose To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic.

Methods

All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group.

Results

Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group.

Conclusions

Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management. Similar content being viewed by others

References

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Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377:28–40. Funding This study was supported by NICHD/NIH R01 HD067721 Grant 99999.003035/2015-08 (BAL) and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: CAPES/PROAP (RFS). Author information Authors and Affiliations Corresponding author Ethics declarations The Institutional Review Board approval was obtained from the Committee for the Protection of Human Subjects (GHS #00013885). Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Supplemental Figure 1 (download DOCX ) (DOCX 160 kb) Rights and permissions About this article Cite this article Likes, C.E., Cooper, L.J., Efird, J. et al. Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression. J Assist Reprod Genet 36, 483–490 (2019). https://doi.org/10.1007/s10815-018-1388-x Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-018-1388-x

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Condition tags

endometriosis

MeSH descriptors

Embryo Implantation Embryo Transfer Endometrium Proto-Oncogene Proteins c-bcl-6 Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Adult Embryo Implantation Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Gene Expression Regulation, Developmental Gene Expression Regulation, Developmental Gonadotropin-Releasing Hormone

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