Daimin Wei1, Jia-Yin Liu2, Yun Sun3, Yuhua Shi1, Bo Zhang4, Jian-Qiao Liu5, Jichun Tan6, Xiaoyan Liang7, Yunxia Cao8, Ze Wang1, Yingying Qin1, Han Zhao1, Yi Zhou9, Haiqin Ren10, Guimin Hao11, Xiufeng Ling12, Junzhao Zhao13, Yunshan Zhang14, Xiujuan Qi15, Lin Zhang16, Xiaohui Deng17, Xiaoli Chen18, Yimin Zhu19, Xiaohong Wang20, Li-Feng Tian21, Qun Lv22, Xiang Ma2, Heping Zhang23, Richard S Legro24, Zi-Jiang Chen25. 1. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China. 2. Department of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing, China. 3. Center for Reproductive Medicine, Ren Ji Hospital, Shanghai, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, China. 4. Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, Guangxi, China. 5. Department of Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, and Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 6. Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, China. 7. Reproductive Medicine Research Centre, the 6th Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 8. Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital, Anhui Medical University, Hefei, China. 9. Center for Reproductive Medicine, Qingdao Women's and Children's Hospital, Qingdao University, Qingdao, China. 10. Department of Reproductive Medicine, Shenyang Dongfang Jinghua Hospital, Shenyang, China. 11. Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, China. 12. Department of Reproductive Medicine, the affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. 13. Reproductive Medical Center, the Second Affiliated Hospital of Wenzhou Medical College and Yuying Children's hospital, Wenzhou, China. 14. Center for Reproductive Medicine, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China. 15. Center for Reproductive Medicine, the Affiliated Hospital of Qingdao University, Qingdao, China. 16. Department of Occupational Hygiene, School of Public Health and Management, Weifang Medical University, Weifang, China. 17. Center for Reproductive Medicine, Qilu Hospital of Shandong University, Jinan, China. 18. Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 19. Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 20. Reproductive Medical Center, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China. 21. Reproductive Medical Center, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China. 22. Center for Reproductive Medicine, Sichuan Provincial People's Hospital, Chengdu, China. 23. Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA. 24. Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA, USA. 25. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China; Center for Reproductive Medicine, Ren Ji Hospital, Shanghai, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, China. Electronic address: chenzijiang@hotmail.com.
Abstract
BACKGROUND:Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer. METHODS: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405. FINDINGS:825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029). INTERPRETATION:Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies. FUNDING: The National Key Research and Development Program of China.
RCT Entities:
BACKGROUND: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer. METHODS: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405. FINDINGS: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029). INTERPRETATION: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies. FUNDING: The National Key Research and Development Program of China.