Ovulation Induction: update on the original modern fertility treatment

Most couples seeking fertility treatment want their plan to be as simple as possible. For decades now the typical entry level of fertility treatment for a variety of underlying conditions has been ovulation induction (OI) with intrauterine insemination (IUI). The goal of these combined treatments is simple; cautiously enhance the number of fertile eggs a woman produces and then optimally time the exposure of these eggs to healthy sperm. Thus OI is the use of medication—under carefully monitored conditions—to boost the ability of a woman’s ovaries to produce more than one egg per reproductive cycle. The culmination of the ovulation induction is typically followed by the use of medication to trigger egg release and then trailed by an IUI (the processing of a sperm specimen by laboratory technicians to optimize the sperm quality and the placement of the specimen by a healthcare provider into the woman’s uterus). The success rates of OI/IUI vary considerably depending primarily upon the underlying cause(s) of infertility and patient’s age. Several studies have recently attempted to help clarify the appropriateness of OI/IUI in specific groups of patients in order to better advise women of their treatment options. Here are some of the highlights of that research:

  • OI/IUI for Unexplained Infertility—many couples complete their initial diagnostic testing only to find that their doctor has ruled out several causes of infertility without definitively identifying why they haven’t been getting pregnant. Left with a diagnosis of “unexplained infertility” they are often guided toward OI/IUI. A recent study (NEJM 2015) sought to compare the various medications used to induce ovulation in these women in order to determine if one regimen was better than others. Their finding was that the oral medications (clomiphene and letrozole) had a lower risk of multiple gestations (twins, triplets and higher) than the injectable medications but they also had a lower chance of pregnancy per attempt. Given that other studies have found that OI/IUI with injectable medications has a much higher risk twins, triplets (and higher order pregnancies) than IVF; most couples are willing accept the greater safety of the lower cost, oral medications even though it might take a bit longer to become pregnant.
  • OI/IUI for PCOS—many women with Polycystic Ovarian Syndrome (PCOS) do not ovulate regularly. For them OI/IUI seems like a logical choice. However numerous women with PCOS will not respond well to clomiphene but they often over-respond to the injectable medications. In order to find another option, a randomized study was undertaken to compare how women with PCOS responded to clomiphene vs. how they would respond to another pill called letrozole—an oral medication that has been shown to have fewer side effects. Their results showed that letrozole was associated with higher live birth rate and a lower risk of twins and triplets as well. So this has become the treatment-of-choice for most women with PCOS that decide to pursue OI/IUI.
  • OI/IUI vs. IVF—a study was designed to determine if women that did not conceive with clomiphene would benefit from injectable medications along with IUI before moving on to IVF. This study was called the FASTT Trial. It was a large, randomized study involving couples with unexplained infertility that were randomly assigned to three cycles of clomiphene/IUI or injectable/IUI prior to advancing to IVF or going straight to IVF. What they found was that the per cycle success rates for CC/IUI was about 8% compared to the success rate for injectable medications/IUI of 10% per cycle and the per cycle success rates for IVF of about 31%. What was more surprising was that they found that the cost per pregnancy was, on average, about $10,000 less for those that went straight to IVF than those that went through the conventional treatment route. Their conclusion was that the use of injectable medications was not of enough benefit to justify the cost and risk of a multiple pregnancy.
  • OI/IUI vs IVF for patients 38 or older—a large randomized study—called the FORT-T trial—was conducted in order to determine how best to guide patients in their late reproductive years. For this clinical trial 150 couples were assigned to either two cycles of CC/IUI, injectable meds/IUI (followed by IVF if not pregnant from the IUI treatment) or proceeding directly to IVF. The most important finding of the study was that nearly 85% of all the live births from this group of patients was through IVF; not OI/IUI.
  • OI/IUI vs. IVF for women with Diminished Ovarian Reserve (DOR)—in order to try to further guide women with signs of ovarian insufficiency on their best treatment option, a secondary analysis of the FASTT Trial and the FORT-T Trial was undertaken. For this analysis they combined the data from these studies in order to gain insight into how ovarian reserve testing can best be used to counsel patients on their treatment options—especially given their shortened reproductive lifespan. Their conclusion was that women with DOR were “unlikely to achieve a pregnancy through OI/IUI” but that “IVF offered a reasonable chance of success.”

In summary, for people that are trying to decide how best to initiate their fertility treatment, there are options. I know because I have been through treatment with my own spouse. Each treatment option has its appeal and I encourage you to look at the links to the studies and try to use the information to help guide you to whatever treatment option you are most comfortable. OI/IUI is appealing because it is less costly and may “more natural.” However it also has a lower success rate and a higher risk of multiple births. One advantage of IVF that is worth considering is that it not only provides the highest pregnancy rate but also the possibility of preserving extra embryos for future attempts. Another advantage to consider with IVF is that it can provide additional information regarding egg and sperm quality that cannot be measured with any other test available. With so many options, I hope you feel encouraged and more prepared to discuss your treatment options with your fertility specialist.

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