Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles

Abstract We assessed the effects of endometrial injection of embryo culture supernatants on assisted reproductive technology (ART) outcomes in frozen-thawed embryo transfer (FET) cycles. Hormone replacement therapy cycles with blastocyst transfer on day 5 after fertilization were included, excluding...

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Main Authors: Ayumu Ito, Yukiko Katagiri, Kentaro Nakaoka, Mami Unagami, Koichiro Ichizawa, Kenji Amano, Yukiko Tokuda, Satoko Oigawa, Masato Yoneyama, Takahiro Tsuchiya, Mami Sekiguchi, Mayuko Furui, Nahomi Umemura, Yuko Tamaki, Koichi Nagao, Masahiko Nakata
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-96138-9
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author Ayumu Ito
Yukiko Katagiri
Kentaro Nakaoka
Mami Unagami
Koichiro Ichizawa
Kenji Amano
Yukiko Tokuda
Satoko Oigawa
Masato Yoneyama
Takahiro Tsuchiya
Mami Sekiguchi
Mayuko Furui
Nahomi Umemura
Yuko Tamaki
Koichi Nagao
Masahiko Nakata
author_facet Ayumu Ito
Yukiko Katagiri
Kentaro Nakaoka
Mami Unagami
Koichiro Ichizawa
Kenji Amano
Yukiko Tokuda
Satoko Oigawa
Masato Yoneyama
Takahiro Tsuchiya
Mami Sekiguchi
Mayuko Furui
Nahomi Umemura
Yuko Tamaki
Koichi Nagao
Masahiko Nakata
author_sort Ayumu Ito
collection DOAJ
description Abstract We assessed the effects of endometrial injection of embryo culture supernatants on assisted reproductive technology (ART) outcomes in frozen-thawed embryo transfer (FET) cycles. Hormone replacement therapy cycles with blastocyst transfer on day 5 after fertilization were included, excluding cycles potentially affecting implantation. The stimulation of endometrial embryo transfer (SEET) group (118 cycles) received endometrial injections of the embryo culture supernatant, while the blastocyst transfer (BT) group (878 cycles) did not. Maternal age was significantly higher in the SEET than in the BT group (p < 0.05). The implantation, ongoing pregnancy, and live birth rates were significantly lower (all p < 0.05) in the SEET than in the BT group. Clinical pregnancy and miscarriage rates were not significantly different between the groups. Age-adjusted odds ratios (ORs) (95% confidence interval [CI]) for implantation and miscarriage were 1.02(0.69–1.52) and 1.97 (1.04–3.72), respectively, in the SEET group. Multivariate analysis was performed, including female age, BMI, AMH, and other potential factors influencing ART outcomes. The adjusted odds ratios (95% CI) for clinical pregnancy and miscarriage in the SEET group were 1.00 (0.63–1.58) and 2.08 (1.02–4.24), respectively. Additionally, the adjusted odds ratio for miscarriage was 0.732 (0.22–2.47) in patients aged < 37 years and 4.63 (1.61–13.3) in those aged ≥ 37 years. In conclusion, endometrial injection of the embryo culture supernatant may adversely affect ART outcomes in FET cycles, especially in maternal age ≥ 37 years.
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spelling doaj-art-779269bc97fb4a318b7a3fe9db1c2ec62025-08-20T02:10:23ZengNature PortfolioScientific Reports2045-23222025-03-011511810.1038/s41598-025-96138-9Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cyclesAyumu Ito0Yukiko Katagiri1Kentaro Nakaoka2Mami Unagami3Koichiro Ichizawa4Kenji Amano5Yukiko Tokuda6Satoko Oigawa7Masato Yoneyama8Takahiro Tsuchiya9Mami Sekiguchi10Mayuko Furui11Nahomi Umemura12Yuko Tamaki13Koichi Nagao14Masahiko Nakata15Department of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityReproduction Center, Toho University Omori Medical CenterReproduction Center, Toho University Omori Medical CenterReproduction Center, Toho University Omori Medical CenterReproduction Center, Toho University Omori Medical CenterReproduction Center, Toho University Omori Medical CenterDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityReproduction Center, Toho University Omori Medical CenterDepartment of Obstetrics and Gynecology, Faculty of Medicine, Toho UniversityAbstract We assessed the effects of endometrial injection of embryo culture supernatants on assisted reproductive technology (ART) outcomes in frozen-thawed embryo transfer (FET) cycles. Hormone replacement therapy cycles with blastocyst transfer on day 5 after fertilization were included, excluding cycles potentially affecting implantation. The stimulation of endometrial embryo transfer (SEET) group (118 cycles) received endometrial injections of the embryo culture supernatant, while the blastocyst transfer (BT) group (878 cycles) did not. Maternal age was significantly higher in the SEET than in the BT group (p < 0.05). The implantation, ongoing pregnancy, and live birth rates were significantly lower (all p < 0.05) in the SEET than in the BT group. Clinical pregnancy and miscarriage rates were not significantly different between the groups. Age-adjusted odds ratios (ORs) (95% confidence interval [CI]) for implantation and miscarriage were 1.02(0.69–1.52) and 1.97 (1.04–3.72), respectively, in the SEET group. Multivariate analysis was performed, including female age, BMI, AMH, and other potential factors influencing ART outcomes. The adjusted odds ratios (95% CI) for clinical pregnancy and miscarriage in the SEET group were 1.00 (0.63–1.58) and 2.08 (1.02–4.24), respectively. Additionally, the adjusted odds ratio for miscarriage was 0.732 (0.22–2.47) in patients aged < 37 years and 4.63 (1.61–13.3) in those aged ≥ 37 years. In conclusion, endometrial injection of the embryo culture supernatant may adversely affect ART outcomes in FET cycles, especially in maternal age ≥ 37 years.https://doi.org/10.1038/s41598-025-96138-9Repeated implantation failureStimulation of endometrium embryo transferEndometrial injectionEmbryo culture supernatantFrozen-thawed embryo transferAssisted reproductive technology
spellingShingle Ayumu Ito
Yukiko Katagiri
Kentaro Nakaoka
Mami Unagami
Koichiro Ichizawa
Kenji Amano
Yukiko Tokuda
Satoko Oigawa
Masato Yoneyama
Takahiro Tsuchiya
Mami Sekiguchi
Mayuko Furui
Nahomi Umemura
Yuko Tamaki
Koichi Nagao
Masahiko Nakata
Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
Scientific Reports
Repeated implantation failure
Stimulation of endometrium embryo transfer
Endometrial injection
Embryo culture supernatant
Frozen-thawed embryo transfer
Assisted reproductive technology
title Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
title_full Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
title_fullStr Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
title_full_unstemmed Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
title_short Endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
title_sort endometrial injection of embryo culture supernatant adversely affects assisted reproductive technology outcomes in frozen thawed embryo transfer cycles
topic Repeated implantation failure
Stimulation of endometrium embryo transfer
Endometrial injection
Embryo culture supernatant
Frozen-thawed embryo transfer
Assisted reproductive technology
url https://doi.org/10.1038/s41598-025-96138-9
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