General Obstetrics and Gynecology: Obstetrics
Perinatal outcomes of in vitro fertilization twins: A systematic review and meta-analyses

https://doi.org/10.1016/j.ajog.2004.11.064Get rights and content

Objective

Uncontrolled studies suggest that in vitro fertilization twins have increased rates of preterm birth and low birth weight and would warrant increased antenatal monitoring. The objective of this meta-analysis was to determine whether the incidence of poor obstetric outcomes is higher for in vitro fertilization twins than for spontaneously conceived twins who were matched for maternal age.

Study design

Medline and EMBASE were searched with comprehensive search strategies. Case-control and cohort studies of twins who were conceived by in vitro fertilization or in vitro fertilization/intracytoplasmic sperm injection, with the transfer of fresh embryos or cryopreserved (frozen) in women with infertility, and/or whose partners were subfertile or infertile, compared with naturally (spontaneously) conceived twins who were matched for maternal age (case-control studies) or which were controlled for it (cohort studies). Two reviewers independently assessed titles, abstracts, and study quality and extracted the data. Statistical analysis was performed with commercial statistical software. Dichotomous data were meta-analyzed with odds ratios as measures of effect size, and continuous data was meta-analyzed with mean differences. Interstudy variation was incorporated with the assumption of a random effects model for the treatment effect.

Results

Compared with spontaneously conceived twins who were matched for maternal age, in vitro fertilization twins have an increased risk of preterm birth between 32 and 36 weeks of gestation (odds ratio, 1.48; 95% CI, 1.05-2.10), and an elevated risk of preterm birth at <37 weeks of gestation when parity is also matched for an odds ratio of 1.57 (95% CI, 1.01-2.44). There was an increased rate of cesarean delivery among in vitro fertilization twins (odds ratio, 1.33; 95% CI, 1.06-1.67). There were no significant differences in incidences of perinatal death, low birth weight infants, or congenital malformations.

Conclusion

In vitro fertilization twins have increased rates of preterm birth compared with spontaneously conceived twins who were matched for maternal age, despite the fact that their outcomes would be expected to be better because of the decreased proportion of monochorionic twins.

Section snippets

Methods

The Meta-analysis of Observational Studies in Epidemiology consensus statement was followed.14

Results

A maximum of 8 case-control studies reported on a given outcome, with most outcomes reported on by fewer studies. The 3 studies that examined perinatal death had results that varied widely (OR, 1.40; 95% CI, 0.22-9.11; Figure 1; Note, Table VII includes key outcomes that include fixed and random effects summary statistics)

Seven studies that reported on PTB (defined as delivery at <37 weeks of gestation) resulted in a combined OR of 1.44 (95% CI, 0.94-2.22; Figure 2). The I2 value of 55.6%

Comment

IVF twins have an increase in PTB from 32 to 36 weeks of gestation compared with spontaneously conceived twins who were matched for maternal age (OR, 1.48; 95% CI, 1.05-2.10). The OR for PTB at <37 weeks of gestation in studies that also matched for parity was similar and approached statistical significance at a 5% level of significance (OR, 1.47; 95% CI, 1.01-2.44). The origin of the increase in PTB has yet to be determined. Possible causes include a factor inherent to the IVF technology, a

References (40)

  • O. Torok et al.

    Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples

    Am J Obstet Gynecol

    (1998)
  • M.I. Evans et al.

    Improvement in outcomes of multifetal pregnancy reduction with increased experience

    Am J Obstet Gynecol

    (2001)
  • Anonymous

    Assisted reproduction: results of treatment 1994-1997. Statistics: health and diseases-the National Board of Health and Welfare Centre for Epidemiology

    (2000)
  • Shultz R. Effect of embryo culture on gene expression and behaviour. Proceedings of the Second World Congress on Fetal...
  • P.B. McFaul et al.

    An audit of the obstetric outcome of 148 consecutive pregnancies from assisted conception: implications for neonatal services

    BJOG

    (1993)
  • S.W. D'Souza et al.

    Children conceived by in vitro fertilisation after fresh embryo transfer

    Arch Dis Childhood Fetal Neonat Ed

    (1997)
  • H.C. Johnson

    Report on the health of Albertans

    (1996)
  • M.S. Kramer

    Determinants of low birth weight: methodological assessment and meta-analysis

    Bull World Health Organ

    (1987)
  • M.C. McCormick

    The contribution of low birth weight to infant mortality and childhood morbidity

    N Engl J Med

    (1985)
  • M.C. McCormick et al.

    The health and developmental status of very low-birth-weight children at school age

    JAMA

    (1992)
  • Cited by (168)

    • Risk, safety, and outcome monitoring in the IVF clinic

      2022, Management of Infertility: A Practical Approach
    View all citing articles on Scopus
    View full text