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Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies

BMJ 2004; 328 doi: (Published 29 January 2004) Cite this as: BMJ 2004;328:261
  1. Frans M Helmerhorst, associated professor (f.m.helmerhorst{at},
  2. Denise A M Perquin, registrar1,
  3. Diane Donker, medical officer1,
  4. Marc J N C Keirse, professor2
  1. 1Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, NL 2300 Leiden, Netherlands
  2. 2Department of Obstetrics, Gynaecology and Reproductive Medicine, Flinders University and Flinders Medical Centre, Adelaide, South Australia
  1. Correspondence to: F M Helmerhorst
  • Accepted 13 November 2003


Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions.

Design Systematic review of controlled studies published 1985-2002.

Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls.

Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality.

Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm (< 32 weeks) and 2.04 (1.80 to 2.32) for preterm (< 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight (< 1500 g), 1.70 (1.50 to 1.92) for low birth weight (< 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends.

Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.


  • Embedded Image Nine tables of detailed results and a list of excluded studies can be found on

  • Contributors FMH and MJNCK designed the review and its protocol. DAMP, DD, and MJNCK conducted the literature searches. DAMP and DD independently extracted data during separate study leaves at Flinders University. Disagreements were resolved in consultation with FMH and MJNCK, if necessary after clarification from the authors of the original studies. All authors contributed to earlier drafts of the manuscript, which was finalised by MJNCK. FMH and MJNCK are the guarantors.

  • Funding Flinders University and Leiden University Medical Center.

  • Competing interests None declared.

  • Ethical approval Not needed.

    Embedded Image Nine tables of detailed results and a list of excluded studies can be found on

  • Accepted 13 November 2003
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