Saturday, November 01, 2003

Infertility Article?

A rose by any other name is still a rose. However, an article that doesn't really inform its readers is just an empty headline.

The article Long Time to Conception Tied to Birthing Problems reports the results of a Dutch-National Institutes of Health (NIH) study. From the article's lede, you'd expect the study to show that a history of infertility puts you at an increased risk of experiencing delivery problems.

While increasingly sophisticated techniques for treating infertility now bring hope to couples, Danish researchers caution that infertile women who do eventually conceive may face a higher risk of birthing problems.

Researchers at the University of Aarhus, in conjunction with colleagues at the U.S. National Institutes of Health, found in a study of Danish births that women who had tried to conceive for more than one year -- a generally accepted definition of infertility -- were at greater risk for premature birth, low birth weight or Caesarean section.

Right from the start you begin to see that this study might not meet your expectations.

The definition of infertility--it's not only the time it takes you to become pregnant, it's also the quality of intercourse. For example, if you only have sex twice in one year, or if you have sex only during the infertile period of your cycle, you're not infertile, you're just not doing it right, so to speak.

Between 10 percent and 20 percent of women report their time to conception over one year long, the study says, and it was not only those women who had undergone fertility treatment that were at risk, but also those who eventually conceived naturally.

The causes of infertility--the study apparently doesn't differentiate between female and male factors. Because what causes infertility in women is very different from what causes infertility in men, it would be very difficult for a study to establish a cause-and-effect relationship between infertility, in general, and birthing risks. For example, let's say a woman is infertile because of female factors--she has an anatomical problem with her uterus, like myomas (fibroids) which are mostly benign uterine muscle growths inside the uterine cavity. Once she becomes pregnant, she has a high likelihood of having a Caesarian section (C/S) delivery related to her infertility. In contrast, if the woman is infertile because of male factors--her partner's sperm is of poor quality--once she becomes pregnant, her likelihood of having an infertility-related C/S delivery is zero.

Her team analyzed nearly 56,000 births from the Danish National Birth Cohort study, where women were asked to report the length of time they took to conceive.

The method used to determine infertility--the researchers didn't look at the women's medical records (a fairly reliable way to establish infertility). Instead, they just asked the women to remember how long they thought it took them to become pregnant. This is not a very reliable method to establish true infertility. (Our recollections are subject to recall bias.)

So, the "long time to conception" part of the study is problematic: infertility is poorly defined, and it's not clear if the study subjects were really infertile, or just thought they were. Unfortunately, the "birthing problems" part is also problematic.

A lot of factors can cause premature and low weight births: age, smoking, medical problems (e.g. diabetes), anatomical problems (e.g. incompetent cervix), etc. Also, unless we know what type of C/S we're talking about, an increased C/S rate in previously infertile women means nothing. In other words, if infertile women have a higher number of elective C/S, it doesn't mean their C/S risk is increased. It simply means that, understandably, women who take a bit longer to become pregnant (or who have to undergo infertility treatments) are more inclined to opt for a C/S delivery.

This means the study has to control for all these other factors. Otherwise, even if an increased risk of these birthing problems is seen, it's not possible to say that the higher risk is related to infertility.

"The raw data showed high risks -- approximately 30 percent to over twice the risk," says lead researcher Olga Basso, a research associate professor at the University of Aarhus Epidemiology Science Center. "But when we adjusted the figures to account for such factors as age and obesity and smoking, the increase we saw was lower, but a still statistically significant association."

In other words, the high risks-- approximately 30 percent to over twice the risk were not connected to infertility, but rather to other known causative factors (age, obesity, etc.). Once these confounding (or rather, confusing) factors are corrected for, the increase is lower. Notice how the article gives you the high, yet meaningless in this context, 30% increase in risk. However, the article makes no mention of the % of the actual increased risk in birthing problems related to infertility. It only tells you that there's a lower, but still statistically significant association.

But let's not get tangled up in percentages. Let's look at what the researchers tell us, in plain English, about these risks (emphasis mine):

"I think women should be concerned, but alarmed is too strong a term," says Christopher Ford, a senior research fellow in reproductive medicine at the University of Bristol. "The biggest risk, it seems, is a mild increase in prematurity between 34 and 37 weeks; that is not an enormous problem. If they were at higher risk for being born before 34 weeks, it would present a real problem, but I don't see that here."

The risk of adverse birth is a relatively small risk and something you have to bear in mind, but not catastrophic," Ford adds. "It can sound quite bad that there is a 50 percent change in the odds, but that is different than change in the risk, and that's important."

Crystal clear, no?

The bottom line for what this study found: in infertile women who eventually conceive, an association with a relatively small increase in birthing problems was noted. Since an association doesn't establish a cause-effect relationship, infertility may, or may not, cause the birthing problems.

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2 Comments:

At 10:32 PM, Anonymous Olga said...

Hello
By pure chance I happened on this comment. I realize it's very late compared to when you wrote this, but still thought it might be worth replying to you. I am one of the authors of the paper the article talks about.

Let me just say that we never used the expression "birthing problems" (which I find somewhat odd in this context), nor we ever advocated causality of infertility in these outcomes.. Plus, authors have a limited control over what journalists say after you talked to them. We mentioned as a limitation of the study that we did not know the causes of infertility but we had thousands of women some of whom had not gone to a doctor. And, in many cases, the cause of infertility is not ascertained. As you need to be two people to conceive, using the time a couple takes to become pregnant is a much used way to define "infertility" (>1 year of trying without conceiving), and this threshold is often studied as an outcome per se. Women appear to be pretty good at reporting the time they took to conceive, even after many years.

This said, I agree that the risk we found is small, and we never claimed otherwise. However, assisted reproductive techinques have been associated with a number of adverse outcomes in babies, but usually comparisons are made with a sample of the general population. Our interest was to see whether infertility per se was associated with adverse outcomes.
Also, I doubt that pregnancies in which the problem is on the male side would have no increased risks.
We had not even imagined that the press would have been interested in our paper, in part because -as you note- the increased risks were pretty small. On the other hand, the scientific community has not paid much attention to the outcome of pregnancies from couples who take a long time to conceive but do not recur to infertility treatment, and we think that this should change.

Sincerely
Olga

 
At 1:29 AM, Blogger ema said...

Professor Basso,

Thank you for stopping by and commenting. Just to clarify, my blog is aimed at a lay audience. As such, one of the things I try to do is to show people how to read/evaluate popular press health articles with a critical eye. So, my problem was with the way the journalist wrote about your study, not the study itself.

[To give you an example, this: We mentioned as a limitation of the study that we did not know the causes of infertility but we had thousands of women some of whom had not gone to a doctor. You, I, and even the journalist (since you told him) get this limitation when we read in the article that women were asked to report the length of time they took to conceive. But a lay reader probably doesn't, unless the journalist (a) points it out, and (b) explains what it means. The problem isn't the study's methodology, it's the fact that the journalist didn't properly educate the readers.]

 

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