Assisted Reproductive Technology and Congenital Anomalies

Assisted reproductive technology (ART) encompasses a spectrum of medical interventions designed to aid conception, most notably in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Since its clinical introduction over four decades ago, ART has enabled the birth of millions of children worldwide, yet it has also been associated with an elevated risk of obstetric complications and congenital anomalies. Compared with spontaneous conceptions, ART pregnancies carry higher rates of preterm delivery, low birth weight and hypertensive disorders. A consistent finding across diverse populations is an increased incidence of structural birth defects, particularly those affecting the cardiovascular, musculoskeletal and urogenital systems. Multiple gestation remains an important mediator of adverse outcomes, but even singleton ART births demonstrate a modestly increased risk. Disentangling the direct effects of ART procedures from underlying parental factors—such as advanced maternal age or male subfertility—has been a central challenge. Emerging technologies and refinements in embryo culture, cryopreservation and single‐embryo transfer are shifting the risk profile, underscoring the need for long‐term surveillance of ART offspring. Globally, these developments carry implications for clinical practice, patient counselling and public‐health policy.

Research from Nature Portfolio

A large retrospective cohort study of over 110 000 pregnancies reported that infants conceived by ART experience more than double the odds of any birth defect compared with naturally conceived peers. The excess risk spanned cardiovascular, musculoskeletal, urogenital, gastrointestinal and respiratory malformations. Mediation analysis indicated that about 38% of the overall effect was attributable to multiple pregnancies, while the majority arose from direct ART‐related mechanisms. Notably, when comparing ART twins with naturally conceived singletons the compounded risk was lower than the additive sum of the two individual effects, supporting strategies that prioritise single‐embryo transfer.

Assisted Reproductive Technology and Congenital Anomalies publication trend

The graph below shows the total number of articles in assisted reproductive technology and congenital anomalies across all publications each year (not limited to Nature Index journals).

Technical terms

Assisted Reproductive Technology (ART): A range of medical methods to achieve pregnancy, including IVF and ICSI.

In Vitro Fertilisation (IVF): Laboratory fertilisation of an egg by sperm followed by embryo transfer to the uterus.

Intracytoplasmic Sperm Injection (ICSI): Direct injection of a single sperm into an oocyte to facilitate fertilisation.

Congenital Anomaly: A structural or functional birth defect present at or before birth.

Multiple Pregnancy: Gestation of two or more embryos, often leading to higher obstetric risk.

References

1. Perinatal outcome in children born after assisted reproductive technologies. Upsala Journal of Medical Sciences (2020).
2. Association of assisted reproductive technology and multiple pregnancies with the risks of birth defects and stillbirth: A retrospective cohort study. Scientific Reports (2018).
3. Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis. Reproductive Sciences (2023).
4. Evaluation of the Risk of Birth Defects Related to the Use of Assisted Reproductive Technology: An Updated Systematic Review. International Journal of Environmental Research and Public Health (2022).
5. Prevalence of Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: A Cohort Study. Journal of Clinical Medicine (2021).
6. Male subfertility and the risk of major birth defects in children born after in vitro fertilization and intracytoplasmic sperm injection: a retrospective cohort study. BMC Pregnancy and Childbirth (2019).