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BJOG. 2019 Apr 21. doi: 10.1111/1471-0528.15800. [Epub ahead of print]

Clomiphene citrate and neural tube defects: a meta-analysis of controlled observational studies.

Author information

1
Service Hospitalo-Universitaire de Pharmaco-Toxicologie, Hospices Civils de Lyon, France.
2
CNRS - Université Lyon 1, UMR5558 - Laboratoire de Biométrie& Biologie Evolutive, Département Biostatistiques & Modélisation pour la Santé et l'Environnement; Equipe Evaluation et Modélisation des Effets des Médicaments.

Abstract

BACKGROUND:

At the end of the 80's several studies have suggested a potential increased risk of neural tube defects (NTDs) with ovulation induction/fertility drugs, especially with clomiphene citrate (CC). A previous meta-analysis of observational studies evaluating the risk of NTDs associated with the use of CC performed in 1995 found a risk ratio of 1.08 (95% confidence intervals (CI) 0.76-1.51). Since then, additional studies have been published and the risk of NTDs associated with periconceptional CC exposure may have changed.

OBJECTIVE:

To perform an updated quantitative meta-analysis of the risk of NTDs associated with periconceptional CC exposure.

SEARCH STRATEGY:

MEDLINE, Web of Science and Scopus (October 2018).

SELECTION CRITERIA:

Comparative cohort and case-control studies investigating the risk of NTDs after periconceptional CC exposure.

DATA COLLECTION AND ANALYSIS:

Pooled effect sizes with corresponding 95% CI were calculated using random effects models, comparing the risk of NTDs between CC exposed and non-exposed pregnancies.

MAIN RESULTS:

Thirteen studies met the inclusion criteria totaling 218 819 pregnancies. Periconceptional exposure to CC was not significantly associated with an increased risk of NTDs (pooled odds ratio 1.21, 95% CI 0.88-1.66). No heterogeneity between studies was observed (I2=26%). Funnel plot and asymmetry test were not suggestive of publication bias.

CONCLUSION:

Our meta-analysis confirms that exposure to CC before or in early pregnancy was associated to a 21% increased risk of NTD in relation to CC exposure, however this increased risk is not statistically significant. This article is protected by copyright. All rights reserved.

KEYWORDS:

assisted reproductive technologies; birth defect; clomiphene citrate; meta-analysis; neural tube defects

PMID:
31006176
DOI:
10.1111/1471-0528.15800

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