Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial

Daimin Wei, Jia Yin Liu, Yun Sun, Yuhua Shi, Bo Zhang, Jian Qiao Liu, Jichun Tan, Xiaoyan Liang, Yunxia Cao, Ze Wang, Yingying Qin, Han Zhao, Yi Zhou, Haiqin Ren, Guimin Hao, Xiufeng Ling, Junzhao Zhao, Yunshan Zhang, Xiujuan Qi, Lin ZhangXiaohui Deng, Xiaoli Chen, Yimin Zhu, Xiaohong Wang, Li Feng Tian, Qun Lv, Xiang Ma, Heping Zhang, Richard Legro, Zi Jiang Chen

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1310-1318
Number of pages9
JournalThe Lancet
Volume393
Issue number10178
DOIs
StatePublished - Mar 30 2019

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Embryo Transfer
Randomized Controlled Trials
Single Embryo Transfer
Embryonic Structures
Pregnancy Rate
Pre-Eclampsia
China
Ovarian Hyperstimulation Syndrome
Intention to Treat Analysis
Blastocyst
Fertilization in Vitro
Menstrual Cycle
Random Allocation
Freezing
Obstetrics
Fertility
Registries

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Wei, D., Liu, J. Y., Sun, Y., Shi, Y., Zhang, B., Liu, J. Q., ... Chen, Z. J. (2019). Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. The Lancet, 393(10178), 1310-1318. https://doi.org/10.1016/S0140-6736(18)32843-5
Wei, Daimin ; Liu, Jia Yin ; Sun, Yun ; Shi, Yuhua ; Zhang, Bo ; Liu, Jian Qiao ; Tan, Jichun ; Liang, Xiaoyan ; Cao, Yunxia ; Wang, Ze ; Qin, Yingying ; Zhao, Han ; Zhou, Yi ; Ren, Haiqin ; Hao, Guimin ; Ling, Xiufeng ; Zhao, Junzhao ; Zhang, Yunshan ; Qi, Xiujuan ; Zhang, Lin ; Deng, Xiaohui ; Chen, Xiaoli ; Zhu, Yimin ; Wang, Xiaohong ; Tian, Li Feng ; Lv, Qun ; Ma, Xiang ; Zhang, Heping ; Legro, Richard ; Chen, Zi Jiang. / Frozen versus fresh single blastocyst transfer in ovulatory women : a multicentre, randomised controlled trial. In: The Lancet. 2019 ; Vol. 393, No. 10178. pp. 1310-1318.
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title = "Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial",
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.",
author = "Daimin Wei and Liu, {Jia Yin} and Yun Sun and Yuhua Shi and Bo Zhang and Liu, {Jian Qiao} and Jichun Tan and Xiaoyan Liang and Yunxia Cao and Ze Wang and Yingying Qin and Han Zhao and Yi Zhou and Haiqin Ren and Guimin Hao and Xiufeng Ling and Junzhao Zhao and Yunshan Zhang and Xiujuan Qi and Lin Zhang and Xiaohui Deng and Xiaoli Chen and Yimin Zhu and Xiaohong Wang and Tian, {Li Feng} and Qun Lv and Xiang Ma and Heping Zhang and Richard Legro and Chen, {Zi Jiang}",
year = "2019",
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doi = "10.1016/S0140-6736(18)32843-5",
language = "English (US)",
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Wei, D, Liu, JY, Sun, Y, Shi, Y, Zhang, B, Liu, JQ, Tan, J, Liang, X, Cao, Y, Wang, Z, Qin, Y, Zhao, H, Zhou, Y, Ren, H, Hao, G, Ling, X, Zhao, J, Zhang, Y, Qi, X, Zhang, L, Deng, X, Chen, X, Zhu, Y, Wang, X, Tian, LF, Lv, Q, Ma, X, Zhang, H, Legro, R & Chen, ZJ 2019, 'Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial', The Lancet, vol. 393, no. 10178, pp. 1310-1318. https://doi.org/10.1016/S0140-6736(18)32843-5

Frozen versus fresh single blastocyst transfer in ovulatory women : a multicentre, randomised controlled trial. / Wei, Daimin; Liu, Jia Yin; Sun, Yun; Shi, Yuhua; Zhang, Bo; Liu, Jian Qiao; Tan, Jichun; Liang, Xiaoyan; Cao, Yunxia; Wang, Ze; Qin, Yingying; Zhao, Han; Zhou, Yi; Ren, Haiqin; Hao, Guimin; Ling, Xiufeng; Zhao, Junzhao; Zhang, Yunshan; Qi, Xiujuan; Zhang, Lin; Deng, Xiaohui; Chen, Xiaoli; Zhu, Yimin; Wang, Xiaohong; Tian, Li Feng; Lv, Qun; Ma, Xiang; Zhang, Heping; Legro, Richard; Chen, Zi Jiang.

In: The Lancet, Vol. 393, No. 10178, 30.03.2019, p. 1310-1318.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Frozen versus fresh single blastocyst transfer in ovulatory women

T2 - a multicentre, randomised controlled trial

AU - Wei, Daimin

AU - Liu, Jia Yin

AU - Sun, Yun

AU - Shi, Yuhua

AU - Zhang, Bo

AU - Liu, Jian Qiao

AU - Tan, Jichun

AU - Liang, Xiaoyan

AU - Cao, Yunxia

AU - Wang, Ze

AU - Qin, Yingying

AU - Zhao, Han

AU - Zhou, Yi

AU - Ren, Haiqin

AU - Hao, Guimin

AU - Ling, Xiufeng

AU - Zhao, Junzhao

AU - Zhang, Yunshan

AU - Qi, Xiujuan

AU - Zhang, Lin

AU - Deng, Xiaohui

AU - Chen, Xiaoli

AU - Zhu, Yimin

AU - Wang, Xiaohong

AU - Tian, Li Feng

AU - Lv, Qun

AU - Ma, Xiang

AU - Zhang, Heping

AU - Legro, Richard

AU - Chen, Zi Jiang

PY - 2019/3/30

Y1 - 2019/3/30

N2 - 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.

AB - 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.

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