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Perinatal Outcomes in Singletons Following In Vitro Fertilization: A Meta-Analysis

Jackson, Rebecca A. MD*; Gibson, Kimberly A. MD, MPH; Wu, Yvonne W. MD, MPH; Croughan, Mary S. PhD

doi: 10.1097/01.AOG.0000114989.84822.51

OBJECTIVE: To estimate whether singleton pregnancies following in vitro fertilization (IVF) are at higher risk of perinatal mortality, preterm delivery, small for gestational age, and low or very low birth weight compared with spontaneous conceptions in studies that adjusted for age and parity.

DATA SOURCES: We searched MEDLINE, BIOSIS, Doctoral Dissertations On-Line, bibliographies, and conference proceedings for studies from 1978–2002 using the terms “in vitro fertilization,” “female infertility therapy,” and “reproductive techniques” combined with “fetal death,” “mortality,” “fetal growth restriction,” “small for gestational age,” “birth weight,” “premature labor,” “preterm delivery,” “infant,” “obstetric,” “perinatal,” and “neonatal.”

METHODS OF STUDY SELECTION: Inclusion criteria were singleton pregnancies following IVF compared with spontaneous conceptions, control for maternal age and parity; 1 of the above outcomes; and risk ratios or data to determine them. Study selection and data abstraction were performed in duplicate after removing identifying information.

TABULATION, INTEGRATION, AND RESULTS: Fifteen studies comprising 12,283 IVF and 1.9 million spontaneously conceived singletons were identified. Random-effects meta-analysis was performed. Compared with spontaneous conceptions, IVF singleton pregnancies were associated with significantly higher odds of each of the perinatal outcomes examined: perinatal mortality (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.6, 3.0), preterm delivery (OR 2.0; 95% CI 1.7, 2.2), low birth weight (OR 1.8; 95% CI 1.4, 2.2), very low birth weight (OR 2.7; 95% CI 2.3, 3.1), and small for gestational age (OR 1.6; 95% CI 1.3, 2.0). Statistical heterogeneity was noted only for preterm delivery and low birth weight. Sensitivity analyses revealed no significant changes in results. Early preterm delivery, spontaneous preterm delivery, placenta previa, gestational diabetes, preeclampsia, and neonatal intensive care admission were also significantly more prevalent in the IVF group.

CONCLUSION: In vitro fertilization patients should be advised of the increased risk for adverse perinatal outcomes. Obstetricians should not only manage these pregnancies as high risk but also avoid iatrogenic harm caused by elective preterm labor induction or cesarean.

In vitro fertilization singletons have higher odds of perinatal mortality, preterm delivery, low and very low birth weight, small for gestational age, and other adverse outcomes than spontaneous conceptions.

From the *Departments of Obstetrics, Gynecology and Reproductive Sciences and Epidemiology and Biostatistics, University of California, San Francisco; †Department of Obstetrics and Gynecology, Kaiser Permanente, San Francisco; ‡Departments of Neurology and Pediatrics, University of California, San Francisco; and §Departments of Family and Community Medicine, University of California, San Francisco, California.

Received September 6, 2003. Received in revised form November 20, 2003. Accepted December 4, 2003.

Address reprint requests to: Rebecca Jackson, MD, Department of Obstetrics and Gynecology, #6D, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110; e-mail:

Supported by a grant from the National Institute of Child Health and Human Development (1 PO1 HD 37074–05).

Presented in an earlier version at the meeting of the American Society for Reproductive Medicine, October 20–25, 2001, Orlando, Florida.

© 2004 The American College of Obstetricians and Gynecologists