Premium
Clomiphene citrate and neural tube defects: a meta‐analysis of controlled observational studies
Author(s) -
Auffret M,
Cottin J,
Vial T,
Cucherat M
Publication year - 2019
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/1471-0528.15800
Subject(s) - meta analysis , medicine , funnel plot , odds ratio , pregnancy , obstetrics , confidence interval , study heterogeneity , relative risk , observational study , publication bias , miscarriage , cohort study , gynecology , biology , genetics
Background At the end of the 1980s, several studies suggested a potential increased risk of neural tube defects ( NTD s) with ovulation induction/fertility drugs, especially with clomiphene citrate ( CC ). A previous meta‐analysis of observational studies evaluating the risk of NTD s associated with the use of CC performed in 1995 found a risk ratio of 1.08 (95% CI 0.76–1.51). Since then, additional studies have been published and the risk of NTD s associated with periconceptional CC exposure may have changed. Objective To perform an updated quantitative meta‐analysis of the risk of NTD s associated with periconceptional CC exposure. Search strategy MEDLINE , Web of Science, and Scopus were searched (October 2018). Selection criteria Comparative cohort and case–control studies investigating the risk of NTD s after periconceptional CC exposure. Data collection and analysis Pooled effect sizes with corresponding 95% CIs were calculated using random effects models, comparing the risk of NTD s between pregnancies exposed and not exposed to CC . Main results Thirteen studies met the inclusion criteria, totalling 218 819 pregnancies. Periconceptional exposure to CC was not significantly associated with an increased risk of NTD s (pooled odds ratio 1.21, 95% CI 0.88–1.66). No heterogeneity between studies was observed ( I 2 = 26%). A 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 with a 21% increased risk of NTD in relation to CC exposure; however, this increased risk is not statistically significant. Tweetable abstract A new meta‐analysis finds that clomiphene citrate exposure before or in early pregnancy is not associated with an increased risk of NTD s.