Studies Link Infertility Treatments to Autism

I am sharing this study as one amongst many out there weighing evidence both ways on fertility drugs. Information is power and it’s good to be knowledgable about our choices–they are never easy ones.

By Claudia Wallis Thursday, May. 20, 2010 / Time Health & Science

Every parent of a child with autism wonders what might have caused the disorder. Does it secretly run in the family? Was there a toxic exposure during pregnancy? An infection in early infancy? Was the mother or father too old?

Amy Sawelson Landes of Tarzana, Calif., has asked herself all of these questions, plus one more: Could the fact that she had taken an infertility drug to get pregnant have contributed to her son Ted’s autism? “It was one of the first things I wondered about,” says Landes, who was 37 when Ted was born 18 years ago.

A study presented Wednesday at the International Meeting for Autism Research in Philadelphia provides some of strongest evidence to date that Landes might be onto something. The study, conducted by a team at the Harvard School of Public Health, found that autism was nearly twice as common among the children of women who were treated with the ovulation-inducing drug Clomid and other similar drugs than women who did not suffer from infertility, and the link persisted even after researchers accounted for the women’s age.

Moreover, the association between fertility drugs and autism appeared to strengthen with exposure: the longer women reported being treated for infertility, the higher the chances their child had an autism spectrum disorder (ASD).

A second paper presented at the conference by an Israeli team found an association between autism risk and in vitro fertilization, which also involves the use of drugs that stimulate ovulation. Taken together, the studies add to a growing body of evidence that a history of infertility and treatment for infertility could play a role in causing autism. However, the papers raise more questions than they answer.

The Harvard study was the first to look specifically at Clomid-type drugs and autism. It was a large study involving data from 3,985 women — all of them nurses; 111 reported having a child with autism. However the data was based on questionnaires completed by the women, rather than clinical records, so there was no way to confirm the history or timing of treatment for infertility or autism diagnosis. Nor did researchers have access to information on whether the affected children were born prematurely, whether they were twins or triplets, or whether they had low birth weights.

“Preterm delivery, low birth weight, twinning and maternal age are all associated with infertility treatment and they are all associated with the risk of autism. We need to understand how to tease these factors apart,” observes Lisa Croen, senior research scientist with Kaiser Permanente in Oakland, Calif., and director of its Autism Research Program, who was not associated with the paper. “This study is addressing a really important question but we really need more data.”

The Israeli report on in vitro fertilization (IVF) is also intriguing, but perhaps even more preliminary. The study looked at 564 children with ASD, who had come to an autism center for in-depth evaluation. It found that 10.2% of the children were the product of IVF, much higher than the rate in the general population of Israel, which is 3.5%. Still, it isn’t clear to what degree the greater risk of autism might be traceable to confounding factors such as maternal age, premature birth or multiple birth.

IVF has been associated in previous studies with a greater risk of birth malformations, certain genetic defects and developmental problems, including autism. There is also some evidence from animal studies that the growth media used to culture embryos outside the body before implantation may play a role in causing genetic or developmental anomalies. But, again, it’s difficult to separate out the intertwined factors of twinning, prematurity and low birth weight that are also associated with autism, and come into play with IVF and other treatments for infertility.

Epidemiologist Kristen Lyall, who led the Harvard study, cautions that even if further research should confirm a link between infertility drugs and autism, any additional treatment-related risk appears to be small: among women whose average age was 35 when they had their first child, there was a 4% risk of having a child with autism for those who had taken fertility drugs, compared with 2% for those with no drug exposure. The increase in risk was even smaller among a younger subset of women.

Still, infertility is a common problem affecting about 10% of American women, many of whom seek drug treatment and interventions such as IVF. “With so many women being exposed, it’s important that we understand the associated risks,” says Geraldine Dawson, chief scientific officer for Autism Speaks.

RESPONSE BY:
Geoffrey Sher, MD Geoffrey Sher is the co-founder and Executive Medical Director of the Sher Institutes for Reproductive Medicine (SIRM).

Friday, May 21, 2010

AUTISM: DOES IVF TREATMENT INCREASE THE INCIDENCE?

At a recent meeting of the International Society for Autism Research (INSAR) on Thursday, May 20, 2010, a few papers were presented suggesting that in vitro fertilization is associated with an increased risk of autism in offspring. The world wide alarm that this evoked amongst infertile couples is understandable and is reminiscent of a similar “panic attack” that was sparked by a publication in the prestigious New England Journal of Medicine (NEJM) in the 90’s which suggested that the use of fertility drugs increased the risk of ovarian cancer. This ovarian cancer study was seriously flawed in that it:

a) was retrospective
b) failed to evaluate the effect of infertility itself on the incidence of ovarian cancer
c) did not adequately correct for the age of the women
d) failed to take into account family history
e) did not carefully consider the clinical cause of infertility and
f) did not account for the effect of ethnic/racial influences.

It was not until a decade or so later, following completion of several international studies in Australia, Europe, Israel and the United States that the findings of the original study were finally negated. However, by that time the message had unnecessarily traumatized an already vulnerable infertile community and created pandemonium amongst medical care givers.

The data reported at the INSAR meeting on IVF and Autism is interesting, but anecdotal. As with the original study reporting an increase in ovarian cancer in women taking fertility drugs, this study on IVF and Autism had potential shortcomings in that:

  • It was also retrospective in design, thereby introducing recall and participation bias.
  • The sample size was limited
  • The reported incidence of autism in IVF babies versus the control group was also very small
  • The incidence of autism is known to be more common in babies born to older mothers, and also in low birth weight offspring – both of which are collectively and individually much more common in IVF. Thus the perceived increase in the occurrence of autism in IVF babies was more likely to have been related to the “type of woman” who undergoes IVF rather than to the IVF treatment itself.

In the same vein, it would come as no surprise to wake up one morning to learn of a new study that attempts links IVF treatment and fertility drugs to an increase in the incidence of breast cancer. After all, breast cancer is more common in women in the 2nd half of their reproductive lives. The same is the case for many women undergoing IVF. Also, breast malignancy is more common in women who are overweight, but such women are also more likely to have hormonal dysfunction that causes infertility, often necessitating IVF [e.g. polycystic ovarian syndrome (PCOS)]. Then there is the reported finding that breast feeding somewhat protects against breast cancer… and of course, infertility precludes or delays the oportunity to breast feed.

It would be reasonable to assert that there are clinical, epidemiologic and demographic circumstances involving patients undergoing infertility and IVF treatments that are also associated with an increased incidence of breast and ovarian cancers. However, to then take it a step further and assert, based upon such associations, that a cause/effect relationship exists between infertility/IVF treatments and ovarian or breast cancer, would not be rational. Similarly, given present data, to claim that infertility and/or IVF treatment is causally linked to autism is somewhat analogous and very premature.

*Autism is a neurological, developmental disorder characterized by deficiencies in social interaction, verbal and nonverbal communication, and dysfunctional interests and behavioral patterns.

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