Pregnancy related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology A meta analysis of cohort studies

We present an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology versus spontaneous conception.

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Jiabi Qin, M.D., Ph.D., Hua Wang, M.D., Xiaoqi Sheng, M.D., Desheng Liang, M.D., Hongzhuan Tan, M.D., Jiahui Xia, M.D.

Volume 103, Issue 6, Pages 1492-1508



To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception.




University-affiliated teaching hospital.


Multiple pregnancies conceived by ART or naturally.


Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.

Main Outcome Measure(s):

Pregnancy-related complications and adverse pregnancy outcomes.


Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05–1.37; I2 = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04–1.19; I2 = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25–2.55; I2 = 42%); preterm birth (RR = 1.08, 95% CI: 1.03–1.14; I2 = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04–1.34; I2 = 79%); low birth weight (RR = 1.04, 95% CI: 1.01–1.07; I2 = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01–1.25; I2 = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02–1.22; I2 = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.


Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.