Which type of congenital malformations is significantly increased in singleton pregnancies following after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis

It is inconclusive nowadays for which type of congenital malformations(CMs) is increased in singleton pregnancies following after in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) compared with those after spontaneous conception; furthermore, a complete overview is missing. We conducted a meta-analysis of cohort studies to assess the risk of specific CMs associated with IVF/ICSI singleton pregnancies. Unrestricted searches were conducted, with an end date parameter of 1 June 2017, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup and sensitivity analyses were performed to explore potential heterogeneity moderators when significant heterogeneity was observed. Sixteen cohort studies with a total of 129,648 IVF/ICSI and 5,491,949 spontaneously conceived singleton births fulfilled the inclusion criteria. The IVF/ICSI singleton pregnancies had a significantly increased risk of cleft lip and/or palate (OR = 1.34 [95% CI: 1.07-1.69]; I2 = 0%), eye, ear, face and neck (odd ratios [OR] = 1.20 [95% CI: 1.04-1.39]; I2 = 15%), chromosomal (OR = 1.23 [95% CI: 1.07-1.40]; I2 = 32%), respiratory (OR = 1.28 [95% CI: 1.01-1.64]; I2 = 37%), digestive (OR = 1.46 [95% CI: 1.29-1.65]; I2 = 0%), musculoskeletal (OR = 1.47 [95% CI: 1.25-1.72]; I2 = 64%), urogenital (OR = 1.43 [95% CI: 1.18-1.72]; I2 = 62%), and circulatory (OR = 1.39 [95% CI: 1.23-1.58]; I2 = 46%) system malformations. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. In conclusion, the IVF/ICSI singleton pregnancies are associated with higher risks for most specific CMs. Clinicians should provide appropriate information to counseling IVF/ICSI patients.