Infertility and Autism Risk

May 21, 2010 by  
Filed under Blog, Research

Does being treated for infertility raise the risk that your child will have an autism spectrum disorder? A number of mothers I have interviewed have voiced this concern. Now two new studies–one that looks at in vitro fertilization and the other at ovulation-stimulating drugs like Clomid–suggest that it may be so. These are preliminary studies but provocative.

A study presented at the International Meeting for Autism Research in Philadelphia on May 19  found that autism was nearly twice as common among the children of women who were treated with Clomid-type drugs than women who did not suffer from infertility (4% vs 2%), and the link persisted even after researchers accounted for the women’s age.

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. 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%.

These studies are far from definitive. The drug treatment study, for example, while based on a large sample of nearly 4,000 nurses, drew its data from questionnaires 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 involved in the study.

The IVF study was was even more preliminary and drawn from what researchers call “a sample of convenience.”

Still, it’s interesting to think about how IVF or ovulation promoting drugs might increase the risk of autism. Do the hormones used in fertility treatments cross the blood-brain barrier and affect fetal development? Might the the quality of the eggs the drugs stimulate to ripen be sub-par? Does the growth medium used in IVF procedures sometimes harm the fetus (there’s some evidence for this in animal studies.)? Could there be something about infertility itself that also somehow ups the odds for autism? No one has the answers at this point.


3 Responses to “Infertility and Autism Risk”
  1. GSX-R750 guy says:

    My fiance and I were arguing about this! Now I know that I was right. lol! Thanks for making me sure!

  2. Terence Mix says:

    Having researched fertility drugs for over 35 years, I would like to share my thoughts. On May 20, 2010, researchers from the Harvard School of Public Health presented their findings from a study exploring the possible relationship between the use of fertility drugs and autism spectrum disorder (ASD). The scientists reported to attendees at the International Meeting for Autism Research in Philadelphia that women who used fertility drugs to get pregnant had almost double the risk of having a child with ASD verses nonusers. The drugs studied included Clomid (clomiphene citrate) and Pergonal (gonadotropin).

    Some have expressed skepticism about the study. However, although its value cannot be fully assessed until it appears in a peer-reviewed journal, there are several factors that argue in favor of its merits. In an effort to rule out other causes, Dr. Lyall and her colleagues made an “adjustment for pregnancy complications, maternal age, and other possible risk factors,” before making a determination that use of fertility drugs represented a 91% increased risk. This was at a highly significant statistical level – namely, the odds that their data did not occur by chance was 993 out of 1,000 (P=0.007). They also determined that a history of infertility – exclusive of fertility drugs – was not significantly associated with ASD, and that the “odds ratio for autism spectrum disorder increased with the number of reports of use of ovulation inducing drugs” (P=0.008).

    This recent study is part of a growing body of research that strengthens the argument that Clomid and other fertility drugs are a cause of ASD via their ability to deny cholesterol to a developing embryo shortly after conception. About 58% of ASD children have low total cholesterol (<160 mg/dL) and about 19% have extremely low total cholesterol (<100 mg/dL). The average level for children is about 165 mg/dL. It has also been observed that a high percentage of children (71-86%) born with Smith-Lemli-Opitz syndrome (SLOS), in addition to a wide array of birth defects are also born with ASD. Infants with SLOS are born with a defective enzyme that impairs the body’s ability to convert a precursor (7-dehydrocholesterol) to cholesterol. Cholesterol is essential for growth of the myelin membranes that cover the brain and abnormalities in the myelin sheath are believed to be a contributing cause of ASD. Many experts thus believe that low cholesterol during early embryonic development is one of the causes of ASD.

    Clomid has a long half-life and is present during the embryonic period (first 8 weeks) even when taken before conception. Studies have shown it to be biologically active for up to 54 days after ingestion and that it can accumulate over successive cycles of treatment. As mentioned, in the Harvard study they found that the longer the use of fertility drugs, the higher the risk of developing ASD. A critically important fact – and one not known by most physicians prescribing the drug – is that Clomid is a cholesterol inhibitor and impairs its production by acting upon enzymes in the body similar to Lipitor and other statin drugs. Its chemical structure is also similar to the cholesterol-reducing drug, Triparanol, which was briefly available during the 1960s. Animal studies have shown that Clomid and Triparanol both act on the same enzyme and affect developing organs in a similar way, with Triparanol being slightly more potent.

    Pergonal (also known as human menopausal gonadotropin or hMG) likewise reduces cholesterol, but by way of a different mechanism. Namely, it suppresses cholesterol levels in early pregnancy via its ability to elevate estrogen production. Studies have established that following hyperstimulation of the ovaries by Pergonal, the resulting elevated estrogen during the luteal (post-ovulation) phase of the cycle suppresses the level of total cholesterol. In fact, there is an inverse correlation between concentrations of estrogen and the level of total cholesterol – the higher the level of estrogen, the lower the concentration of total cholesterol.

    The GOOD NEWS is that many ASD children with low cholesterol, treated with cholesterol supplementation, have shown dramatic improvement. Scientists at Johns Hopkins University Medical Center, led by Dr. Richard Kelley, have shown such treatment resulting in improved mobility, verbalization, growth, behavior, sociability and alertness. Better yet, once we have a full understanding about one of the causes of ASD, some day in the future we might be in a position to eliminate that cause. As I postulated over two years ago, maintaining an optimum level of cholesterol throughout pregnancy could likely eliminate many cases of birth defects and autism spectrum disorder.

  3. Claudia Wallis says:

    Thank you for your interesting comment. I did see the Harvard study, but this cholesterol theory is new to me. I’ll be interested to see where the research leads. /Claudia Wallis