Unexplained Infertility

Just a few years ago, unexplained infertility was reported in up to 60% of patients in studies from the medical literature. Even as recently as the last few years, authors have continued to report its prevalence as high as 20% to 25%. A recent textbook summarized several studies dating back to 1950 and quoted an average percent of unexplained infertility of 16.7%. Of note, some recent authors report their percent unexplained between 0% and 6%.

How can such wide discrepancies in the percentage of unexplained infertility be explained?

Obviously, if one considers, as has been proposed, a semen analysis, evaluation of ovulatory function, a post coital exam, a hysterosalpingogram, and a laparoscopy a complete initial assessment in any couple not conceiving in one year of attempting, a larger number of patients will be diagnosed as unexplained infertility than if additional tests are included or a longer period of infertility is required before making the diagnosis. If one accepts an abnormal parameter as an explanation, expanding the diagnostic tests only slightly reduces "unexplained" infertility dramatically as shown, for illustrative purposes, in the attached table from my own practice.

Apart from the definition of infertility itself, an additional consideration would be the definition of test normalcy in any given practice or clinic. For example, if one uses 60% sperm motility of grade three plus as the lower limits of normal and accepts that any lower value may be associated with infertility, many otherwise "unexplained" male infertility problems become "explained".

We also know, as with smoking, excess caffeine intake, or alcohol use, or can deduce numerous causes of infertility which are not precisely evaluated by currently available tests. For example, consider success rates with gamete intrafallopian transfer in couples with unexplained infertility. These success rates on average in this country will be 26% to 28% in terms of a live birth per ococyte retrieval. This is strikingly increased over controlled ovarian hyper stimulation combined with intrauterine insemination with washed husband's semen success rates. Other than simply increasing the number of gametes available, what does GIFT accomplish? It obviates the need for sperm transport through the fallopian tube, for oocyte release from the ovary, and for ococyte pickup by the fallopian tube. So, as alluded to above, one can deduce, in all probability, defects must exist in one or more of those mechanisms in at least a percentage of couples with unexplained infertility.

IVF data clearly indicate, even in the most successful programs, low implantation rates relative to the number of embryos transferred. Defects which lead to problems with implantation are probably much more common than we realize and constitute another area of unexplained infertility for which testing is currently being investigated. Assaying implantation factors such as integrins may, in fact, lower the percentage of patients identified with unexplained infertility, but do not assist in the initial deliberations regarding therapy.