Don't Turn To ART Too Quickly!

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Hans van der Slikke, MD, PhD: “It’s July of 2002 and we’re in Vienna at the ESHRE Conference. Next to me is David Dunson, welcome, David.”

David B. Dunson, PhD: “Thank you.”

Hans van der Slikke, MD, PhD: “David is a statistician from the U.S. and he works together with several European centers on fertility. David, today you presented a whole new way of looking at the chances to conceive with or without artificial tricks. Tell me about the presentation you did.”

David B. Dunson, PhD: “I essentially presented some results from our study where we were looking at probabilities of conception for couples who weren’t using any sort of method of enhancing their fertility or assisted reproduction. These were couples of apparently normal fertility so there wasn’t any data for these couples that they had problems with reproduction in the past and, as I mentioned, they weren’t using any sort of method to enhance their fertility or hormonal contraceptives or anything like that. So based upon following these couples, and these couples were at different ages, we could look at what the natural probabilities of conception were in different age categories and we could use those natural probabilities of conception to look at the time of pregnancy distribution in a population of couples of different ages to see whether or not or how fast these couples are becoming pregnant. What we found was there was a pretty sharp increase in clinical infertility with age, in particular, for women aged 19-26 there was about an 8% probability of not becoming pregnant in the first year. This probability increased to 13%-14% for women aged 27-34 and increased farther to 18% for women aged 35-39. So this is clinical infertility or failure to conceive within the first year of trying so we were slightly concerned about that but what was much nicer is we then extended the estimates for two years to see what would happen for these same couples. We found that over half of the couples actually would conceive in the second year even if they were defined as clinically infertile and unable to conceive in the first year so what happened in the second year is that these proportions went down to 3% not conceiving within two years for 19-26, 6% for 27-34, and 9% for 35-39 so even for women in their late thirties less than 10% don’t conceive naturally within two years.”

Hans van der Slikke, MD, PhD: “You took the age at the beginning of their trying or at the end of their trying?”

David B. Dunson, PhD: “We adjusted for the age that they were within each cycle under study so it was a prospective study so they aged as the study went on.”

Hans van der Slikke, MD, PhD: “So they changed groups after becoming thirty-five years old.”

David B. Dunson, PhD: “That’s right.”

Hans van der Slikke, MD, PhD: “This was not a study, let’s say, in the classical clinical sense but it’s more like a statistical study that you did.”

David B. Dunson, PhD: “It’s more like an observational epidemiology-type study than a clinical study, that’s correct.”

Hans van der Slikke, MD, PhD: “How many of this group went into assisted reproduction procedures?”

David B. Dunson, PhD: “I actually don’t have information on that. My feeling would be that it would be very low because these are women coming into a natural fertility clinic so many of these women don’t believe in using hormonal contraception and are probably opposed to assisted reproduction as well.”

Hans van der Slikke, MD, PhD: “I see, so you said this may have biased this group a little bit.”

David B. Dunson, PhD: “The only way it would bias the group is if women coming into a fertility clinic or a natural family planning center had systematically different fertility parameters compared to women in the general population, and we don’t have any reason to believe that would be the case.”

Hans van der Slikke, MD, PhD: “I was thinking why this group should be different but I think you’re right in your reason to believe that.”

David B. Dunson, PhD: “Sometimes it’s kind of difficult to study changes with age because as couples age the more fertile couples will often have children younger so among the remaining couples who are attempting pregnancy there might be a decline with fertility for those reasons, sort of due to selection and that happens predominantly among the group of couples who are desiring a pregnancy at any age. One of the nicest things about our data is that we had mostly couples who wanted to prevent pregnancy by using natural-type methods though they often changed their mind during the course of this study so for that reason we might have much less of these problems with selection.”

Hans van der Slikke, MD, PhD: “This was a kind of life table type of collecting?”

David B. Dunson, PhD: “One of the remarkable things about this study was we had very detailed information so for each menstrual cycle we had charts. We had each day of the menstrual cycle, we had whether or not intercourse occurred, we had information on basal body temperature, and we had information on cervical mucous. We used that information to estimate the day of ovulation in each cycle and then we had intercourse records relative to ovulation for each cycle and whether or not pregnancy occurred so we could use that to estimate probabilities of conception given intercourse on different days of the menstrual cycle. Then for any given frequency of intercourse, you can turn that into a time of pregnancy distribution just applying standard statistic methods.”

Hans van der Slikke, MD, PhD: “But then I could argue that maybe the women that don’t have a regular cycle are not very suited for natural family planning.”

David B. Dunson, PhD: “You could say that if you had irregular cycles but we weren’t throwing out women with irregular cycles at all. It depends on what sort of method you use. If you had an irregular cycle, something like a standard days method, which would say to not have intercourse on day eight to nineteen of the menstrual cycle might not be the best type of approach because you might sometimes have abnormally long cycles or long follicular phases where ovulation occurred outside of that window. Then the fertile days which occurred in the six day interval ending on the day of ovulation might occur outside of some standard day but other methods based on prospectively looking at cervical mucous characteristics such as Billing’s ovulation method, I would suspect, aren’t as thrown off by variability in the cycle length and there have been studies, I’m showing that as well.”

Hans van der Slikke, MD, PhD: “You did a study in several European centers, and I see we have them here, isn’t that true?”

David B. Dunson, PhD: “Yes.”

Hans van der Slikke, MD, PhD: “It’s Milan, Verona, Lugano - three Italian centers and then one in Dusseldorf, Paris, London, and Brussels so at the end of the day what’s your conclusion and what does it mean for, let’s say, the practical clinician?”

David B. Dunson, PhD: “For the practical clinician it means that when they have somebody coming into their clinic and they say we’ve had difficulty getting pregnant for a year maybe then they look at that couple in detail to see if there’s any reason to explain their infertility. If there’s not, I would say in general a clinician should probably recommend an additional year of trying for that couple.”

Hans van der Slikke, MD, PhD: “Thank you very much, David.”

David B. Dunson, PhD: “Thank you.”