Unexplained infertility

Another reader asks: “1. What would be your recommendation for a couple with unexplained infertility? On paper the couple is perfect but even with IUI cycles and injectibles cannot seem to conceive. Especially if Insurance says no to any procedures for infertility treatment, ie IVF or the IUI's. 2. Is there a point when a couple with unexplained infertility and no disposable income for IVF procedures should just give up on having a baby?”


Depending on how you define unexplained infertility, the prevalence of this diagnosis in a fertility clinic varies from zero to 20% of the patient population. How can there be such a range? A famous professor/fertility expert once said “a cause for infertility can be found in all couples if enough tests are obtained.” I am afraid this reveals a rather unsophisticated understanding of medical testing, as if you do enough tests on normal healthy couples, something will eventually turn up positive. The trick in medicine is to do the right tests on the right patients (this maximizes the “predictive value” of the test). But what are the right tests? One way to approach this would be to do fertility tests on fertile and infertile couples. If the test under study is abnormal more frequently in the infertile group, the test probably has some value in a fertility evaluation. This approach has been performed in a meaningful way for only a few fertility tests: semen analysis (some value) and endometrial biopsy (worthless). I was involved in both these studies, and believe me, they were challenging to do, involving millions of your tax dollars. A friend and mentor once tried to do all the standard fertility tests on both fertile and infertile couples and couldn't collect enough data to make meaningful conclusions. It's an interesting report to read though, as he often found fertile couples with abnormal fertility test results (see here to read it: http://humrep.oxfordjournals.org/content/9/12/2306.full.pdf).

Here is what I recommend for a basic infertility evaluation: semen analysis, hysterosalpingrogram, post-coital test (PCT), and midluteal progesterone level. Yes, I know the PCT is controversial and many fertility clinics don't bother with it, but I still think it's a meaningful (and fairly inexpensive) test. And the progesterone level is an easy way to confirm that ovulation is occurring. If all these tests are normal, I encourage infertile women to have a laparoscopy, unless your insurance won't cover it. In my view, you can't give a diagnosis of “unexplained infertility” without a laparoscopy to confirm it.

So what if all these tests are normal? If the woman is young (less than 30), and the duration of infertility is brief (less than 2 years), I encourage a few months of watchful waiting to see if pregnancy occurs spontaneously. If these criteria are not met, than the next step is to take clomiphene and do intrauterine inseminations. I usually recommend 3 cycles of this. If the woman is older (over 35) or if she has already taken clomiphene, I encourage women to go straight to gonadotropins and IUI. What about doing IVF? Great idea, but it's more expensive than the other two options. It does have a lower risk of triplets or higher, though, as long as you don't get carried away by putting in too many embryos. I occasionally have patients who don't get pregnant with clomiphene/IUI go straight to IVF for this reason. One fertility clinic recently tried to determine whether it was more cost-effective to do the gonadotropin/IUI first or go straight to IVF; the results didn't particularly favor either approach.

Our reader with unexplained inferility asks what to do if IVF is not an option, but gonadotropin/IUI hasn't worked. Well, in general you have reached the end of your fertility treatment. The only thing beyond IVF is IVF with donor eggs, which is even more expensive. When to quit? Other than when your money or insurance coverage runs out, or the fertility treatment is driving you crazy, I would recommend quitting when you get to the point of taking gonadotropins and you only make a couple of mature follicles, despite high doses of medicine (300 units or above). This is an ominous sign that you are running out of eggs faster than other women your age, and the success of IVF under these circumstances is low. For those women, egg donor IVF is the best approach.I think women with such diminished ovarian reserve as their only fertility problem are just as likely to conceive on their own as with IVF, and occasionally former patients will call me to confirm that very event (they like to rub it in a bit, but I am happy for them nonetheless).

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