• Christos Venetis, Stephanie K Y Choi, Louisa Jorm, Xian Zhang, William Ledger, Kei Lui, Alys Havard, Michael Chapman, Robert J Norman, and Georgina M Chambers.
• National Perinatal Epidemiology and Statistics Unit (NPESU), Centre for Big Data Research in Health, and School of Clinical Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia, Unit for Human Reproduction, 1 Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, and Virtus Health, Sydney Australia (C.V.).
• Ann. Intern. Med. 2023 Oct 1; 176 (10): 130813201308-1320.

BackgroundMore than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation.ObjectiveTo investigate the role of underlying infertility and fertility treatment on CA risks in the first 2 years of life.DesignPropensity score-weighted population-based cohort study.SettingNew South Wales, Australia.Participants851 984 infants (828 099 singletons and 23 885 plural children) delivered between 2009 and 2017.MeasurementsAdjusted risk difference (aRD) in CAs of infants conceived through fertility treatment compared with 2 naturally conceived (NC) control groups-those with and without a parental history of infertility (NC-infertile and NC-fertile).ResultsThe overall incidence of CAs was 459 per 10 000 singleton births and 757 per 10 000 plural births. Compared with NC-fertile singleton control infants (n = 747 018), ART-conceived singleton infants (n = 31 256) had an elevated risk for major genitourinary abnormalities (aRD, 19.0 cases per 10 000 births [95% CI, 2.3 to 35.6]); the risk remained unchanged (aRD, 22 cases per 10 000 births [CI, 4.6 to 39.4]) when compared with NC-infertile singleton control infants (n = 36 251) (that is, after accounting for parental infertility), indicating that ART remained an independent risk. After accounting for parental infertility, ICSI in couples without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD, 47.8 cases per 10 000 singleton births [CI, 12.6 to 83.1]). There was some suggestion of increased risk for CAs after fresh embryo transfer, although estimates were imprecise and inconsistent. There were no increased risks for CAs among OI/IUI-conceived infants (n = 13 574).LimitationsThis study measured the risk for CAs only in those children who were born at or after 20 weeks' gestation. Observational study design precludes causal inference. Many estimates were imprecise.ConclusionPatients should be counseled on the small increased risk for genitourinary abnormalities after ART, particularly after ICSI, which should be avoided in couples without problems of male infertility.Primary Funding SourceAustralian National Health and Medical Research Council.

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