Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies.
OBJECTIVE
To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among multiple births conceived with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).


METHODS
PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2016 for cohort studies assessing adverse pregnancy outcomes associated with IVF/ICSI multiple births. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses.


RESULTS
Sixty-four studies, with 60,210 IVF/ICSI multiple births and 146,737 spontaneously conceived multiple births, were selected for analysis. Among IVF/ICSI multiple births, the pooled estimates were 51.5% [95% confidence interval (CI): 48.7-54.3] for preterm birth, 12.1% (95% CI: 10.4-14.1) for very preterm birth, 49.8% (95% CI: 47.6-52.0) for low birth weight, 8.4% (95% CI: 7.1-9.9) for very low birth weight, 16.2% (95% CI: 12.9-20.1) for small for gestational age, 3.0% (95% CI: 2.5-3.7) for perinatal mortality and 4.7% (95% CI: 4.0-5.6) for congenital malformations. When the data were restricted to twins, the pooled estimates also showed a high prevalence of adverse outcomes. There was a similar prevalence of poor outcomes among multiple births conceived with IVF/ICSI and naturally (all P ≥ 0.0792). Significant differences in different continents, countries, and income groups were found.


CONCLUSIONS
The IVF/ICSI multiple pregnancies have a high prevalence of adverse pregnancy outcomes. However, population-wide prospective adverse outcomes registries covering the entire world population for IVF/ICSI pregnancies are needed to determine the exact perinatal prevalence.
Information Management Division, Hunan Provincial Maternal and Child Health Care Hospital, 53 Xiangchun Road, Changsha, 410008, Hunan, China. qinjiabi123@163.com.
Jia-Bi
JB
Qin
Division of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, 53 Xiangchun Road, Changsha, 410008, Hunan, China. shengxq999@163.com.
Xiao-Qi
XQ
Sheng
Division of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, 53 Xiangchun Road, Changsha, 410008, Hunan, China.
Hua
H
Wang
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Guo-Chong
GC
Chen
Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
Jing
J
Yang
Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
Hong
H
Yu
Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan, China.
Tu-Bao
TB
Yang
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D009099:Multiple Birth Offspring / Q000706:statistics & numerical data; D054238:Perinatal Mortality; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D047928:Premature Birth / Q000453:epidemiology*; D015995:Prevalence; D011446:Prospective Studies; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects*
Adverse pregnancy outcomes; In vitro fertilization; Intracytoplasmic sperm injection; Multiple births; Prevalence estimates