The Dilemma of Infertility Treatment for Unexplained Infertility

We now have a simple algorithm for couples with unexplained infertility: Three cycles of Clomid with IUI before going to IVF


Aunexplained infertility | UC Advanced Reproductive Medicine | CO | embryos the new medical director of the University of Colorado Advanced Reproductive Medicine (CU ARM), I have the distinct pleasure of speaking to you about National Infertility Awareness Week. This annual event highlights the importance of infertility, which affects approximately 12-15 percent of reproductive age couples.

Clearly, the problem may extend well beyond these statistics as countless individuals lack any insurance coverage, preventing them from seeking assistance in order to conceive. These data may obscure the actual number of couples attempting to conceive at any given time. While some states offer mandated coverage, the vast majority of state legislatures have chosen to exclude infertility benefits, leaving infertile couples on their own and scrambling to fund the basic diagnostic infertility tests, as well as the far more expensive treatment options.

We at CU ARM are dedicated to providing the most comprehensive and affordable diagnostic evaluation for the infertility couple and individual. Our expertly trained nurses and dedicated physician staff will guide you through the process starting at your initial office visit.

At the completion of that initial intake, your physician will lay out a comprehensive plan to assess why you are unable to conceive. This will often consist of lab work and a pelvic ultrasound designed to measure your egg status, also known as your ovarian reserve. These are merely indirect assessments of your egg status and yield some information on the number of reserve eggs that remain in the “resting pool” of your ovaries.

It is normal to have less eggs as you move through your reproductive years, as a group or cohort of eggs are activated to grow each month while typically only a single egg matures and is released from the ovary during ovulation. Your physician will often order a special X-ray (hysterosalpingogram) exam to determine if your fallopian tubes are blocked or scarred. Ovulation (release of your mature egg) can often be depicted by measuring your progesterone level during the second half of your menstrual cycle (luteal phase). Lastly, a semen analysis is ordered to evaluate the male partner.

When to book your first infertility appointment

Unexplained infertility: What to do when all tests are normal

Treatment options are often directed toward correcting whatever component of your infertility evaluation is abnormal. The dilemma, experienced by about 15-20 percent of couples seeking fertility care, is what to do when all test results are normal. It is human nature to want to uncover a problem or abnormal test during this evaluation with the expectation that your physician would now be enlightened to select the appropriate treatment resulting in a successful pregnancy. Couples whose tests are normal are labelled as having “unexplained infertility.”

These may include failure of fertilization (perhaps due to defective sperm and/or egg), genetically abnormal embryos, undiagnosed disorders that affect pelvic anatomy such as endometriosis, defective ovum pick-up (damaged fallopian tubes, which prevents the tube from capturing the egg once released from the ovary at ovulation), and/or implantation disorders. In some instances, a few subtle conditions coexist, which in aggregate rise to the level of preventing conception.

Over the years, several treatment options have been offered to help patients with unexplained infertility. Currently, the most widely accepted initial therapy involves combining fertility medications with intrauterine insemination (IUI) to overcome some of the potential causes of unexplained infertility previously listed above. Fertility medications may result in superovulation (growth and release of multiple oocytes), which, when combined with placement of sperm directly in to the uterus (IUI), may enhance the chances of sperm-oocyte interaction and hence fertilization followed by a successful conception.

The combination of a fertility medication such as Clomid and IUI yields an 8-10 percent pregnancy rate per treatment cycle, of which only 8 percent are multiple births. Clearly, not all patients conceive with this regimen and ultimately require a more aggressive approach.

Better approach to infertility treatment for unexplained cases

A recent landmark study published in Fertility and Sterility in 2010 by Dr. Reindollar demonstrated the efficacy of proceeding directly to in vitro fertilization (IVF) after three failed cycles of Clomid and IUI. The marked increase in cost for an IVF cycle is offset by the dramatic increase in the per cycle success rate.

The study group that progressed directly to IVF after failed Clomid-IUI cycles did nearly as well as the group that followed Clomid-IUI with injectable gonadotropins (injectable fertility medications) and IUI. The pregnancy per cycle success rate of Clomid -IUI was 7.6 percent, which increased only slightly to 9.8 percent in the injectable-IUI group. Pregnancy rates for the IVF group were 30.7 percent per treatment cycle. The slight increase in success for the injectable-IUI group over Clomid-UI group is to be balanced against the dramatic cost increase and rise in multiple births.

This study presented a cost effective method for patients with unexplained infertility to proceed through treatment cycles while maximizing success rates. Despite the evidence, patients in nonmandated states (states that don’t mandate coverage for infertility treatment services) may find it more affordable, in the short term, to use injectable fertility medications and IUI and failing multiple Clomid-IUI cycles. However, the cost of three failed cycles of injectable meds and IUI may often exceed the cost of a single IVF cycle. More importantly, the cumulative pregnancy rates after three cycles of injectable medications and IUI equals the success rate of a single IVF cycle.

Infertile patients with normal test results are considered to have unexplained infertility. The various causes may escape detection by our basic panel of infertility tests. A simple treatment algorithm now exists and progresses from three cycles of Clomid and IUI directly to IVF. This regimen offers the most cost effective approach to many couples with unexplained infertility. The decision to treat must be weighed against the known statistic demonstrating that 65 percent of couples with unexplained infertility will conceive, on their own, within three years.