In the latest media barrage on autism, infertility treatments have come into question as a possible cause for this increasingly common developmental disorder. The reason is two research abstracts presented at the International Meeting for Autism Research this week in Philadelphia. (If you’re interested, the abstracts are on pages 9 and 11 of the linked pdf file).
One study assessed the history of IVF among 574 children evaluated at a special center for autism in Israel. The researchers found that 10% of the group diagnosed as autistic had had IVF, compared to a background rate in the overall population which they quote as 3.5%. Not surprisingly, maternal age was higher in the IVF group and the rate of prematurity was higher in the autistic children.
The second study was a look into a pre-existing database – the Nurse’s Health Study – which collects data from a cohort of nurses over time. The researchers compared the reproductive history reported by women who also reported having a child with autism and compared it to that of women who did not report having an autistic child. Of those with autistic children, 48% reported infertility with 34% having used ovulation inducing drugs, compared with 33% and 24%, respectively, in women without autistic children, a difference that was statistically significant when controlled for maternal age and self-reported pregnancy complications.
A Time article getting a lot of media play calls the results of the second study “some of the strongest evidence to date” linking autism to fertility treatment.
Unfortunately, that’s just not true.
Studies such as the one being reported this week certainly raise questions, but in reality do nothing to answer them. They are nothing more than preliminary forays that are fraught with problems when one tries to use the results for anything other than to inform further, better designed research. The problem is not necessarily with the studies themselves, which are clearly preliminary – it is with how the media is reporting the results. Which gets into the whole problem of PR and media reporting of research meetings, which I think is getting out of control, but that’s another post for another day…
For now, let’s go through the more obvious limitations of the data being presented.
1. The Nurses Study Population – A 33% rate of infertility in the control group and close to 50% in the study group? The background rate of infertility in the US is about 10%. Is this study population representative? I doubt it.
2. Recall bias – This is when an individual who has experienced an adverse outcome does a better job of remembering exactly what drugs and treatments she took than someone who has not had the adverse outcome. It’s human nature, after all, to spend hours, even days looking back and asking “What did I do that caused this?” But it means you remember a lot more than folks with no reason to be so retrospective. The Nurses Study, being a prospective collection of data, does not have this bias, but the Israeli study may.
3. Controlling for the underlying problem – infertility. The Nurse’s Study found that women having more cycles of IVF or clomid had higher rates of autism. But if you need to undergo multiple cycles of infertility treatment, isn’t it just possible that there is something about your gametes – either egg or sperm – that are the problem, and not the drugs themselves? The fact that autism is a highly hereditable disorder supports that there may be an inherent association between the state of infertility and autism. Maybe infertility is nature’s way of controlling the gene pool, so to speak, and we’re messing with it by helping folks get pregnant who maybe weren’t supposed to. Don’t tell that, of course, to the millions of normal, healthy and intelligent individuals born as a result of IVF. But it might explain small increases in certain conditions among children born after fertility treatments compared to the general population, mightn’t it?
While the researchers did control for age, that’s just not good enough. We all know that while age is an excellent marker for IVF success, it is ultimately the quality of the oocyte and sperm that is the most important factor in determining success in fertility treatment.
4. Cause of infertility – One way to tease out the effect of the gametes from the fertility drugs is to focus only on those women with tubal infertility – their eggs are fine, it’s the passageway that’s the problem. If this group had higher autism rates with ovulation inducing drug use, then that’s a stronger association. Unfortunately, the data presented were not detailed enough to address this question.
5. Consequences of fertility treatments – Ovulation inducing agents all lead to higher rates of multiple pregnanies with their associated complications of prematurity and low birth weight, both factors associated with autism. How much of the reported associations were due to these factors and not the fertility treatments themselves?
6. Diagnostic bias – Could it be that parents who persist through multiple fertility cycles against the ever increasing odds that they may not have a child might also be more persistent in getting their child diagnosed with autism? It’s possible, I believe.
To date, well done research into developmental outcomes of children born as a result of assisted reproductive technologies (ART) has not found significant risks, but most studies have been confined to infancy and early development, prior to when some children may be diagnosed with autism. Recent studies on longer term childhood outcomes among children born as a result of ICSI (intracytoplasmic sperm injection) have been quite reassuring in this regard. One small study did find a higher rate of autism in children born after ICSI, but not IVF, and the numbers were so small (3 children only had autism), that it’s difficult to make larger conclusions from the data. A recent review article found no reliable studies of autism and ART, and calls for more research.
I would agree.
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Photo from NBC.com
I agree with you, and think that you might be particularly on the money with 6. After my kids were diagnosed I did a lot of support work for higher-order multiple birth families with special needs, and the rate of autism seemed to be huge.
Which made perfect sense, as higher-order multiple births (usually related to fertility treatments), are often preemies, and thus a lot more closely followed by doctors (and parents), than most kids are. When you already know that there is a chance that your children might have some issues due to prematurity, you're not going to be slow about getting them tested if their speech is delayed, etc.
Not to mention that in general couples who do fertility treatments are generally more educated, wealthier, likely live in an urban setting near an autism diagnostic centre, etc. etc…all of which increase the odds that you will get an autism diagnosis.
Oprah magazine had an article a couple of years ago about a group of women who used donor sperm from the same donor all met through a provision to find donor siblings. The outcome was shocking; a high number of the children had an autism diagnosis, and the sperm donor admitted to them that he had Aspberger's. The children looked very much alike and they looked like their father. The man was a very talented professor. The women had selected qualities of intelligence, blond hair, blue eyes, height…and they got a little more than they bargained for.
I think the genetic aspect has been under-explored in the race to blame vaccines, other medical procedures, and even our changing environment.
Here is a link to the article I mentioned.
http://www.oprah.com/relationships/Autism-Aspergers-and-The-Donor-Sibling-Registry/4
Most of the studies seem to show that autism definitely does have a genetic component, although narrowing down the exact genes and processes involved has proved a bit trickier. (My kids are fraternal triplets…2 girls 1 boy, and although girls were theoretically less likely to have autism when my kids were diagnosed, all 3 kids were diagnosed with it. Now we're finding out that it's likely that there isn't a big gender divide in autism diagnosis, but that's pretty recent.)
My comment above was meant to relate to incidence of diagnosis, not actual occurrence. It's been shown a few times in studies that if you're well-educated and live in an urban area near an autism diagnosis centre your child is more likely to be diagnosed autistic.
I would be extremely leery of taking any health-related information from Oprah at face value…she is one of Jenny McCarthy's biggest supporters, still, and has not yet shown that she really even understands what a peer-reviewed study is, let alone promoted one. She makes her money off of entertainment, not health.
It's going to be interesting to see if she backs out of hosting Jenny McCarthy's show now that the autism/vaccine link has been so thoroughly disproven.
@Jen: I didn't take the article to be Oprah's take on the issue, not at all. I don't think Oprah knows anything. I think it has been irresponsible of her to promote the medical causes that she has–menopause, vaccines, whatever. I don't know much about the thyroid episode she did, but it seems like it's just not that hard to get a thyroid diagnosis.
I was just giving the source of the article, since the mothers involved came to the conclusion about the genetic issue on their own. Some of them had infertility treatment, but others just had insemination.
I personally don't see how fertility treatment itself can be a link to autism; I don't think it changes genetic material for the better or worse. I fully believe that autism awareness and diagnosis have both increased, and I completely understand how they might be diagnosed more often in a larger city (where there are more doctors in general and more specialists in particular), or in a more affluent set of families who can even afford to search for answers.
I think these kids were written off as quirky, different, problematic, etc., etc. in past times. I'm glad we're coming out of the darkness.
Sorry- I didn't mean to jump all over you 🙂
I don't think that it's fertility treatments either…I think that there is possibly a higher chance that people who have undergone fertility treatments may be more likely to end up with an autism diagnosis, but I do think that there is a genetic base.
And I am very glad that my kids were born when they were…even 20 or 30 years ago, there likely would have been some pressure to 'keep them out of sight'. Fortunately that's (generally) no longer the case.
We're cool!
I wonder if the people who go through infertility treatment are more tuned in to seeking a medical opinion. I think that would lend itself to more diagnosis.
My feeling is that there are lots of causes of infertility, and they may also exist in people who carry genes for autism. I think it's a lot easier to study a group that admits to infertility treatment, because it's going to be a smaller group based on the trouble and expense it requires of people. I can understand fears of technology causing health problems, so maybe a study is a good idea to see if it's possible to set that worry to rest.
Fertility drugs may be a factor in autism, but what about older autistics? I'm thinking of the remarkable Temple Grandin. She was born before such infertility treatments existed.
It makes sense to me that infertility may have something to do with natural selection. Now and again I do think, "You shouldn't mess with mother nature."
BTW, after 5 years of trying unsuccessfully to get pregnant, my husband and I underwent about 2years of infertility treatment back in the late '50s. We ultimately adopted two daughters then, as often happens, I got pregnant. And this daughter was and has continued to be healthy.
Good post.
Until a comparison is made between the many different causes of infertility, studies like these can't tell us enough to make informed decisions.
I discovered your blog today … while searching for information on Mohs incisions. I had my 4th Mohs procedure (over a 20 year time frame) three weeks ago. First Mohs on my forehead, second and third on both sides of my nose and the most recent, on my cheek close to my nose. This incision seems more 'lumpy' than the others.
I so appreciate the photos and posts you wrote in 2008.
Regarding autism, I have 2 friends with autistic boys … no fertility procedures, no family history (as far as they know) … another family with an adult female diagnosed with Asperger's when she was a child (again no family history / an only child.)
Enjoy your weekend ……..
Helen-
glad I've helped in some way. 4 Mohs! I have a feeling that will be me one day soon as well….
Thanks for visiting.
Thank you for posting about this. I'm 31 and my husband and I have been trying to start a family for three years. We're Male factor and are planning to do IVF next year.
It's so frustrating to watch the media toss alegations around regarding Fertility treatments. You never see stories about the couple who just welcomed their first child after trying for five years – Only the spectacles like the Octomom get any coverage.
Then there are the absurd, and as you pointed out, incomplete medical reports that get published and highlighted. And it seems without any consideration for the fact that their "information" is detrimental to actually educating the public about the truth behind Infertility and treatments.
Sorry to rant. I really just meant to thank you. =)
Melissa – Never apologize for ranting – that's what this whole blog this is all about!
🙂
Peggy
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