Live Birth with or without Preimplantation Genetic Testing for Aneuploidy

Junhao Yan; Yingying Qin; Han Zhao; Yun Sun; Fei Gong; Rong Li; Xiaoxi Sun; Xiufeng Ling; Hong Li; Cuifang Hao; Jichun Tan; Jing Yang; Yimin Zhu; Fenghua Liu; Dawei Chen; Daimin Wei; Juanjuan Lu; Tianxiang Ni; Wei Zhou; Keliang Wu; Yuan Gao; Yuhua Shi; Yao Lu; Ting Zhang; Wei Wu; Xiang Ma; Hailan Ma; Jing Fu; Junqiang Zhang; Qingxia Meng; Heping Zhang; Richard S Legro; Zi-Jiang Chen

doi:10.1056/NEJMoa2103613

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy

N Engl J Med. 2021 Nov 25;385(22):2047-2058. doi: 10.1056/NEJMoa2103613.

Authors

Junhao Yan¹, Yingying Qin¹, Han Zhao¹, Yun Sun¹, Fei Gong¹, Rong Li¹, Xiaoxi Sun¹, Xiufeng Ling¹, Hong Li¹, Cuifang Hao¹, Jichun Tan¹, Jing Yang¹, Yimin Zhu¹, Fenghua Liu¹, Dawei Chen¹, Daimin Wei¹, Juanjuan Lu¹, Tianxiang Ni¹, Wei Zhou¹, Keliang Wu¹, Yuan Gao¹, Yuhua Shi¹, Yao Lu¹, Ting Zhang¹, Wei Wu¹, Xiang Ma¹, Hailan Ma¹, Jing Fu¹, Junqiang Zhang¹, Qingxia Meng¹, Heping Zhang¹, Richard S Legro¹, Zi-Jiang Chen¹

Affiliation

¹ From the Center for Reproductive Medicine, Cheeloo College of Medicine, Key Laboratory of Reproductive Endocrinology of the Ministry of Education, and the National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Shandong Key Laboratory of Reproductive Medicine, and Shandong Provincial Clinical Research Center for Reproductive Health, Jinan (J.Y., Y.Q., H.Z., D.W., J.L., T.N., W.Z., K.W., Y.G., Y.S., Z.-J.C.), the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics (Y.S., Z.-J.C., Y.L., T.Z.), and the Obstetrics and Gynecology Hospital of Fudan University, Shanghai JIAI Genetics and IVF Institute, Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University (X.S., J.F.), Shanghai, the Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, and Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha (F.G., H.M.), the Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, National Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Assisted Reproduction, Ministry of Education, and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing (R.L.), the Department of Reproductive Medicine, the Affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital (X.L., J.Z.), and the Department of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University-Jiangsu Province Hospital (X.M., W.W.), Nanjing, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou (H.L., Q.M.), the Center for Reproductive Medicine of Yantai Yuhuangding Hospital, Yantai (C.H.), the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang (J.T.), the Center for Reproductive Medicine, Wuhan University, Wuhan (J.Y.), the Department of Reproductive Endocrinology, Key Laboratory of Reproductive Genetics, Ministry of Education, Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou (Y.Z.), the Department of Reproductive Health and Infertility, Guangdong Women and Children Hospital, Guangzhou (F.L.), and the Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei (D.C.) - all in China; the Department of Biostatistics, Yale University School of Public Health, New Haven, CT (H.Z.); and the Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA (R.S.L.).

PMID: 34818479
DOI: 10.1056/NEJMoa2103613

Abstract

Background: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).

Methods: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age. Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one. The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization. We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF, which would constitute the noninferiority margin for conventional IVF as compared with PGT-A.

Results: A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval [CI], -9.2 to -0.0; P<0.001). The cumulative frequency of clinical pregnancy loss was 8.7% and 12.6%, respectively (absolute difference, -3.9 percentage points; 95% CI, -7.5 to -0.2). The incidences of obstetrical or neonatal complications and other adverse events were similar in the two groups.

Conclusions: Among women with three or more good-quality blastocysts, conventional IVF resulted in a cumulative live-birth rate that was noninferior to the rate with PGT-A. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03118141.).

Publication types

Equivalence Trial
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aneuploidy*
Blastomeres
Chromosome Disorders / diagnosis
Embryo Transfer
Female
Fertilization in Vitro*
Genetic Testing*
High-Throughput Nucleotide Sequencing
Humans
Intention to Treat Analysis
Live Birth*
Pregnancy
Preimplantation Diagnosis*
Prognosis
Young Adult

Associated data

ClinicalTrials.gov/NCT03118141

Abstract

Publication types

MeSH terms

Associated data

Grants and funding