title: Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: a meta-analysis of cohort studies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Meta-analysis.
  
  
  METHODS
  University-affiliated teaching hospital.
  
  
  METHODS
  Multiple pregnancies conceived by ART or naturally.
  
  
  METHODS
  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.
  
  
  METHODS
  Pregnancy-related complications and adverse pregnancy outcomes.
  
  
  RESULTS
  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; I(2) = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I(2) = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I(2) = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I(2) = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I(2) = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I(2) = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I(2) = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I(2) = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Jiabi
authors.initials: J
authors.lastname: Qin
authors.affiliation: Division of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, Hunan, People's Republic of China. Electronic address: wangh1234@hotmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, Hunan, People's Republic of China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Hunan, People's Republic of China.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Hunan, People's Republic of China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Xia
mesh_terms: D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000401:mortality; D007246:Infertility / Q000453:epidemiology* / Q000628:therapy*; D054238:Perinatal Mortality; D011247:Pregnancy; D011248:Pregnancy Complications / Q000401:mortality*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011272:Pregnancy, Multiple / Q000706:statistics & numerical data*; D027724:Reproductive Techniques, Assisted / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Assisted reproductive technology; adverse pregnancy outcomes; intracytoplasmic sperm injection; in vitro fertilization; meta-analysis