Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome

Zi-Jiang Chen, M.D., Ph.D., Yuhua Shi, M.D., Ph.D., Yun Sun, M.D., Ph.D., Bo Zhang, M.D., Xiaoyan Liang, M.D., Ph.D., Yunxia Cao, M.D., Ph.D., Jing Yang, M.D., Ph.D., Jiayin Liu, M.D., Ph.D., Daimin Wei, M.D., Ph.D., Ning Weng, M.D., Lifeng Tian, M.D., Ph.D., Cuifang Hao, M.D., Ph.D., Dongzi Yang, M.D., Ph.D., Feng Zhou, M.S., Juanzi Shi, M.D., Ph.D., Yongle Xu, M.D., Jing Li, M.D., Junhao Yan, M.D., Ph.D., Yingying Qin, M.D., Ph.D., Han Zhao, M.D., Ph.D., Heping Zhang, Ph.D., and Richard S. Legro, M.D.

N Engl J Med 2016; 375:523-533August 11, 2016DOI: 10.1056/NEJMoa1513873

Background

The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.

Methods

In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.

Results

Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).

Conclusions

Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.)

Supported by a grant from the National Basic Research Program of China (973 Program) (2012CB944700), by grants from the National Natural Science Foundation of China (81430029 and 81471428), and by grants from the Thousand Talents Program (to Drs. Legro and H. Zhang).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the Reproductive Medicine Network Steering Committee of the National Institutes of Health for sharing the protocol and case-report forms from the Pregnancy in Polycystic Ovary Syndrome II study.

Source Information

From the Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, and National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan (Z.-J.C., Y. Shi, D.W., J. Li, J. Yan, Y.Q., H. Zhao), Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (Z.-J.C., Y. Sun), and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics (Z.-J.C., Y. Sun), Shanghai, Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, Guangxi (B.Z.), Reproductive Medicine Center, the Sixth Affiliated Hospital of Sun Yat-sen University (X.L.) and Center for Reproductive Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (D.Y.), Guangzhou, Center for Reproductive Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei (Y.C.), Center for Reproductive Medicine, Wuhan University, Wuhan (J. Yang), Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing (J. Liu), Reproductive Medicine Center of Jinghua Hospital, Shenyang (N.W.), Center for Reproductive Medicine, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang (L.T.), Center for Reproductive Medicine of Yantai Yuhuangding Hospital, Yantai (C.H.), Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou (F.Z.), Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shanxi Province, Xi’an (J.S.), and Center for Reproduction and Genetics, Suzhou Municipal Hospital, Suzhou (Y.X.) — all in China; Department of Biostatistics, Yale University School of Public Health, New Haven, CT (H. Zhang); and Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey (R.S.L.).

Address reprint requests to Dr. Chen at the Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, 324 Jingwu Rd., Jinan 250021, China, or at chenzijiang@hotmail.com.

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