IVF and Congenital Anomalies: How Much of the Increased Risk Is Linked to Twins?

A Canadian study examined 274,893 births to women diagnosed with infertility.

Multiple birth statistically explained about one-fifth of the excess risk associated with IVF or ICSI.

Congenital anomaly risk was relatively higher after IVF or ICSI than among births to women diagnosed with infertility who received no fertility treatment, according to a Canadian population study. Twins and other multiple births explained only part of that association.

Among almost 275,000 births, the adjusted relative risk was 28% higher in the IVF/ICSI group. Multiple birth statistically accounted for approximately 20% of that excess risk.

Published in the October 2026 issue of Human Reproduction, the study attempted to distinguish the contribution of multiple birth from other factors linking fertility treatment and congenital anomalies.

A study of 274,893 births in Ontario

The researchers analyzed Ontario birth records from 2006–2021 for women with an infertility diagnosis, including live births and stillbirths after 22 weeks of pregnancy.

There were 229,932 births without fertility treatment, 20,525 following ovulation induction or intrauterine insemination, and 24,536 following IVF or ICSI.

Multiple-birth rates were 2.3%, 7.2% and 13.3%, respectively. The IVF/ICSI rate was approximately 5.8 times that of the untreated infertility group.

Multiple pregnancy is associated with complications such as preterm birth, low birth weight and preeclampsia. The researchers examined how much it might also contribute to the observed excess risk of congenital anomalies.

A 28% relative increase does not mean 28 affected babies in 100

After adjusting for relevant maternal and infant characteristics, congenital anomaly risk was 11% higher following ovulation induction or insemination and 28% higher following IVF/ICSI than in the untreated group.

These are relative increases, not the actual proportions of babies with anomalies.

For illustration only, if the comparison group's risk were 2%, a 28% relative increase would correspond to approximately 2.56%. Those values illustrate the arithmetic; they are not the study's observed absolute rates.

The comparison population is also important. It consisted of births to women diagnosed with infertility who did not receive treatment, rather than all naturally conceived births. This helps examine treatment-related factors against a shared background of infertility.

Multiple birth explained 19.7% of the excess risk

The researchers used mediation analysis to estimate the pathway in which fertility treatment increases multiple birth, which in turn may affect congenital anomaly risk.

Multiple birth statistically explained approximately 19.7% of the excess risk observed after IVF/ICSI—about one-fifth.

Reducing twins therefore cannot explain or necessarily eliminate the entire association. Other possible contributors include conditions underlying infertility, parental reproductive health, genetic characteristics and treatment-related factors.

The remaining approximately 80% should not be interpreted as damage caused directly by IVF. This observational analysis cannot completely separate unmeasured influences or establish direct causation.

The contribution differed by type of anomaly

The estimated mediated proportion was 44.4% for pulmonary artery stenosis, a congenital narrowing affecting blood flow from the heart toward the lungs.

The corresponding estimates were 32.2% for central nervous system anomalies, 28.6% for circulatory system anomalies and 16.7% for musculoskeletal anomalies.

Multiple birth may therefore contribute differently across conditions.

Again, these percentages are not the conditions' occurrence rates. They are estimated proportions of the excess risk statistically mediated by multiple birth. Individual-condition analyses also require attention to small case numbers and uncertainty.

Why single-embryo transfer matters—and what it cannot resolve

Transferring more than one embryo can increase the chance of twins and other multiple pregnancies, with consequences for both maternal and infant health.

Where appropriate, single-embryo transfer is an important strategy for reducing multiple-pregnancy complications, taking account of age, embryo characteristics and previous treatment outcomes.

The study also suggests that avoiding multiple pregnancy will not remove every factor associated with congenital anomalies. Conditions underlying infertility, parental health and genetic influences may precede treatment.

An observed association does not prove that IVF itself directly causes congenital anomalies. Relative increases must also be distinguished from the actual probability of an affected birth.

For couples planning treatment, the relevant discussion includes the cause of infertility, maternal health, an appropriate embryo-transfer strategy and prenatal assessment—not the isolated figure of 28%.

The study supports looking across the whole pathway from underlying infertility through treatment, pregnancy and birth when evaluating offspring health.

Study source

Bailey Milne, Maria Velez, J. Shellenberger, S. B. Brogly and colleagues, including Queen's University and McGill University: “Increased risk of congenital anomalies after fertility treatment is partially mediated by multiple birth: a population-based cohort study.” Human Reproduction, October 2026 issue; published online July 31, 2026. DOI: 10.1093/humrep/deag124.

The illustration was generated using ChatGPT (OpenAI). Any people depicted are fictional.