The Link Between Infertility Treatments and Birth Defects

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A new study seeks to answer a longstanding chicken-or-egg question: do infertility treatments raise the risk of birth defects, or is the risk linked to infertility itself?

Researchers suggest both factors may be at play, depending on the type of infertility treatment used. In vitro fertilization, or IVF, a commonly used technique that mixes egg and sperm in a dish before transferring fertilized embryos to the mother, was not associated with a higher risk of birth defects, once other risk factors like mothers’ age and smoking were taken into consideration.

However, another technique in which sperm is directly injected into the egg — intracytoplasmic sperm injection, or ICSI — was associated with an increased risk of birth defects, as was home use of an ovulation stimulation medication.

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The study, which was published online by the New England Journal of Medicine, looked at the outcomes of 308,974 births in Southern Australia, including 6,163 involving fertility treatments or assisted reproductive techniques. The sample included the overwhelming majority (99.99%) of children born using assisted reproductive techniques in the region between 1986 and 2002. Overall, 8.3% of children born using assisted conception had some type of birth defect, compared with 5.8% of those conceived naturally.

But when researchers controlled for other factors that could increase birth defect risks, they found that IVF was not associated with greater odds. In contrast, ICSI was associated with a 57% increased risk. Researchers could not confirm, however, how much of the problem was linked to the technique — it could be that the extra handling of egg and sperm may result in damage to the cells — and how much was due to the male infertility that typically leads to its use. ICSI helps sperm that are unable to fertilize an egg on their own.

Further, since ICSI techniques have improved tremendously in the last 10 years, it’s also not known whether the same results would be found today.

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The largest increase in risk was associated with home use of a drug called clomiphene citrate (Clomid) to stimulate egg production. Clomid, which is far less expensive than IVF and ICSI, is often the first treatment attempted by women facing infertility. However, when used without adequate medical supervision, it was associated with a 300% greater risk of birth defects. That’s because if Clomid dosing is not timed correctly, the developing child can be exposed to it, which can cause defects.

The study also found that frozen embryos created through IVF were less likely to result in babies with birth defects than those implanted immediately, before freezing. That sounds strange but probably results from the fact that embryos that survive freezing are more likely to be healthy.

The researchers conclude:

Although the large majority of births resulting from assisted conception were free of birth defects, treatment with assisted reproductive techniques was associated with an increased risk of birth defects, including cerebral palsy, as compared with spontaneous conception. In the case of ICSI, but not IVF, the increased risk of birth defects persisted after adjusting for maternal age and several other risk factors. Although we cannot rule out the possibility that other patient factors contribute or explain the observed associations, our findings can help provide guidance in counseling patients who are considering treatment for infertility.

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Overall, experts not involved in the study supported its methods and found its results reassuring. Dr. Avner Hershlag of the Center for Human Reproduction at North Shore University in New York told WebMD: “It’s reassuring for the most part and scientifically done the right way.”

Dr. Joe Leigh Simpson, president-elect of the International Federation of Fertility, said in a statement, “This study largely confirms what we already know, that there is a slightly increased risk of problems in children conceived via assisted conception,” the Los Angeles Times reports. However, the study authors note that the vast majority of babies are born healthy.

Maia Szalavitz is a health writer at Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland’s Facebook page and on Twitter at @TIMEHealthland.