IVF and Birth Defects: Why the Small Extra Risk Is Not Just About Twins, and What It Means for Your Baby

What three large 2026 studies, by Milne, Tark and Richard and their colleagues, tell families about twins, a rare pattern called VACTERL, and checking the heart in boys with hypospadias

Babies conceived through in vitro fertilization (IVF) are slightly more likely to have a birth defect, but most are born without one. Three large studies from 2026 found that twins explain only part of this small extra risk, which is concentrated in rare patterns affecting several body parts at once. IVF-conceived boys born with hypospadias, where the opening of the urine tube is on the underside of the penis, may benefit from a closer check of the heart.

Why families and doctors have been asking this question for years

If your baby was conceived with IVF, you may have wondered whether the treatment could affect their health. This is one of the most natural questions parents ask, and researchers have studied it for more than 20 years. IVF means that eggs and sperm are brought together in a laboratory and an embryo is placed in the womb. A related technique, intracytoplasmic sperm injection (ICSI), injects a single sperm directly into each egg.

The three new studies come from two research groups. In the United States, Tark and colleagues looked at a rare pattern of birth defects called VACTERL [1], and Richard and colleagues, using the same information, looked at boys with hypospadias and heart defects [2]. In Canada, Milne and colleagues asked how much twins explain [3].

One of the first large warnings came from Western Australia. A study of babies born in the 1990s found that about 9 in every 100 babies conceived with IVF or ICSI had a major birth defect diagnosed by their first birthday, compared with about 4 in 100 babies conceived naturally [4]. Later, a South Australian study made an important observation: parents who had difficulty conceiving had more babies with birth defects even when they had no treatment at all [5]. That raised a hard question. Was the extra risk caused by the treatment, or by whatever made it hard to conceive in the first place? When researchers combined 45 studies, the overall picture was a risk about one-third higher than after natural conception [6].

Twins became part of the story too. Twins have more birth defects than babies born on their own, about 1.7 times as many in one English study [7]. In the past, IVF clinics often placed two or more embryos in the womb, which made twins much more common [8]. A study in Massachusetts estimated that about a third of the extra risk after fertility treatment was explained by twins and other multiple births [9]. In Ontario, Canada, once the publicly funded IVF programme required one embryo at a time, twin and triplet pregnancies after IVF fell from about 29 in 100 to about 7 in 100 [10]. But it remained unclear how much of the extra risk would disappear if twins were taken out of the picture. That is one of the questions the new studies set out to answer.

How the three studies were done

None of these studies gave anyone a treatment. Instead, researchers looked back at official records of births that had already happened. In the United States, the team linked birth certificates and birth-defect records from four states (Massachusetts, New York, North Carolina and Texas) to a national database of IVF treatment cycles, covering births from 2004 to 2018. The VACTERL study included about 1.56 million babies: 175 161 conceived by IVF and 1 380 775 conceived naturally [1]. The hypospadias study included 731 838 boys from the same records [2]. Because both studies use the same data and largely the same researchers, they support each other but do not count as two separate confirmations.

The Canadian study, from Ontario, took a different and clever approach [3]. Every one of its 274 893 births was to a woman who had seen a doctor about infertility. Some then had no fertility treatment. Some had milder treatments, such as medicines to help release eggs or insemination, where sperm is placed in the womb. Others had IVF or ICSI. Comparing these groups with each other makes it easier to tell what the treatment itself might be doing, apart from the infertility.

What the researchers found about twins

In Ontario, a birth defect was recorded in 5.9 in every 100 babies whose mothers had infertility but no treatment, 6.7 in 100 after milder treatments, and 7.6 in 100 after IVF or ICSI [3]. So most babies, in every group, had none. Using careful statistics, the team estimated that twins and other multiple births explained only about one-fifth of the extra risk after IVF or ICSI. Most of the difference remained even after twins were accounted for. The extra risk showed up in several body systems, including the heart, the brain and spinal cord, the muscles and bones, and the genitals, but not in cleft lip or palate.

A rare pattern called VACTERL

VACTERL is a name built from the first letters of six body parts that can be affected: the vertebrae (bones of the spine), the anus, the heart (cardiac), the windpipe and food pipe (tracheo-esophageal), the kidneys (renal) and the limbs. A child is said to have VACTERL when at least three of these are affected. It is rare, and in most children no single cause is found [11].

In the American study, 200 children had VACTERL [1]. It occurred in about 2.3 of every 10 000 IVF-conceived babies, compared with about 1.2 of every 10 000 naturally conceived babies. Put another way, for every 10 000 babies born after IVF, about one more had VACTERL than would be expected after natural conception. After allowing for parents' ages, health conditions and other differences, the researchers' measure of likelihood (called the odds) was still about 1.9 times higher. The difference was still clear when only babies born on their own, not twins, were studied. Other complex patterns of several defects were also more common, while simpler patterns showed smaller differences.

If your child has VACTERL, it may help to know that treatment usually centres on surgery soon after birth to repair the specific problems. Children with VACTERL do not tend to have problems with thinking and learning [11].

Hypospadias and the heart

Hypospadias and heart defects are two of the most common birth defects in boys [2]. Researchers already knew that boys with hypospadias are more likely than other boys to also have a heart defect [12]. In the new study, among IVF-conceived boys born with hypospadias, about 7 in every 100 also had a heart defect. Among naturally conceived boys with hypospadias the figure was about 4 in 100 [2]. The combination was still rare overall: it affected 65 IVF-conceived boys, or about 8 in every 10 000.

In the United States, every newborn is offered a quick, painless check with a light sensor on the hand and foot that measures oxygen in the blood. It is good at finding the most serious heart problems, but it does not catch every heart defect [13]. The researchers suggest that IVF-conceived boys with hypospadias may be a group in whom a closer look at the heart is worthwhile [2]. If this applies to your son, you can ask your baby's doctor whether a heart check is planned. You can read more about newborn heart screening on In[Neo]Sight.

What this means for your family

The most important message is reassuring: the large majority of babies conceived with IVF are born without any birth defect. The extra risk the studies found is small, and it is concentrated in a few rare patterns. Having twins explains only part of it. Neither the parents' ages nor their health conditions fully explain it either, and nobody yet knows the reason.

For most families, nothing changes. Your baby will have the same newborn examination as every other baby. The new findings mainly help doctors know when to look more carefully. If a baby conceived with IVF has one problem typical of VACTERL, such as a blocked anus or a kidney difference, doctors usually check the other body parts carefully. If an IVF-conceived boy has hypospadias, it is reasonable to check the heart more closely. Please feel free to tell your baby's care team how your baby was conceived. It is useful information, and you never need to feel embarrassed about sharing it.

What researchers are working on next

The researchers want to understand why this small extra risk exists. One idea is that very early development in the laboratory could change how certain genes are switched on and off, although this has not been shown for VACTERL [1]. The Canadian team wants to study whether particular causes of infertility, such as endometriosis (tissue like the womb lining growing outside the womb) or polycystic ovary syndrome (a hormone condition that affects the release of eggs), play a role [3]. Others are looking at which treatment details matter. For example, the INVICSI trial (ICSI versus conventional IVF without severe male factor; six public fertility clinics in Denmark) found that, for couples without a serious sperm problem, ICSI did not lead to more babies being born, and its authors suggest keeping ICSI for severe male infertility [14]. That trial counted how many babies were born, not birth defects, so future studies will need to look at those. Finally, the next step would be to test whether extra heart checks for IVF-conceived boys with hypospadias find heart problems earlier and improve care.

The bottom line

These studies show a small extra risk of birth defects that twins explain only partly. The excess is mostly in rare patterns involving several body parts, and the absolute risk remains low. For families, the practical message is simple and hopeful. Most IVF babies are born healthy, and doctors now have a clearer idea of when to take a closer look.

References

  1. Tark JY, Richard MA, Schraw JM, et al. In Vitro Fertilization and VACTERL Birth Defects. JAMA Netw Open. 2026;9(8):e2629355. doi:10.1001/jamanetworkopen.2026.29355 ↩
  2. Richard MA, Luke B, Jaime E, et al. A population-based study of the co-occurrence of hypospadias and congenital heart defects among boys conceived with in vitro fertilization†. Hum Reprod. 2026;41(8):1440-1447. doi:10.1093/humrep/deag093 ↩
  3. Milne BM, Velez MP, Shellenberger J, Brogly SB. Increased risk of congenital anomalies after fertility treatment is partially mediated by multiple birth: a population-based cohort study. Hum Reprod. 2026;41(10):1810-1819. doi:10.1093/humrep/deag124 ↩
  4. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002;346(10):725-730. doi:10.1056/NEJMoa010035 ↩
  5. Davies MJ, Moore VM, Willson KJ, et al. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012;366(19):1803-1813. doi:10.1056/NEJMoa1008095 ↩
  6. Hansen M, Kurinczuk JJ, Milne E, de Klerk N, Bower C. Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(4):330-353. doi:10.1093/humupd/dmt006 ↩
  7. Glinianaia SV, Rankin J, Wright C. Congenital anomalies in twins: a register-based study. Hum Reprod. 2008;23(6):1306-1311. doi:10.1093/humrep/den104 ↩
  8. Kissin DM, Schieve LA, Reynolds MA. Multiple-birth risk associated with IVF and extended embryo culture: USA, 2001. Hum Reprod. 2005;20(8):2215-2223. doi:10.1093/humrep/dei025 ↩
  9. Liberman RF, Getz KD, Heinke D, et al. Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births. Birth Defects Res. 2017;109(14):1144-1153. doi:10.1002/bdr2.1055 ↩
  10. Velez MP, Soule A, Gaudet L, Pudwell J, Nguyen P, Ray JG. Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program. JAMA Netw Open. 2024;7(4):e248496. doi:10.1001/jamanetworkopen.2024.8496 ↩
  11. Solomon BD. VACTERL/VATER Association. Orphanet J Rare Dis. 2011;6:56. doi:10.1186/1750-1172-6-56 ↩
  12. Richard MA, Patel J, Benjamin RH, et al. Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias. JAMA Netw Open. 2022;5(7):e2224152. doi:10.1001/jamanetworkopen.2022.24152 ↩
  13. Oster ME, Pinto NM, Pramanik AK, et al. Newborn Screening for Critical Congenital Heart Disease: A New Algorithm and Other Updated Recommendations: Clinical Report. Pediatrics. 2025;155(1):e2024069667. doi:10.1542/peds.2024-069667 ↩
  14. Berntsen S, Zedeler A, Nøhr B, et al. IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial. Nat Med. 2025;31(6):1939-1948. doi:10.1038/s41591-025-03621-x ↩