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Unexplained Infertility Treatment – Choosing the Right Path

A blog by Dr. Eric Flisser, RMA of New York, February 10, 2015

Patients experiencing infertility face a bewildering array of medical terms and acronyms that can make taking even the first step towards achieving a pregnancy a daunting task. First, patients must process the work-up: TSH, AMH, FSH, HSG, E2, P, and then they must learn the treatments: IVF, IUI, ICSI. In researching their proposed treatment plan, they will then notice the infertility bloggers using common acronyms, TTC, DH, BBT, BFP, RE, to describe treatment and the emotional ups and downs that accompany the process. In the face of this, a patient then must make a decision about treatment options, hopefully with an experienced, sympathetic physician-guide. By its nature, however, the final treatment decision, depending on the clinical situation, must be made by the patient.

To simplify, if the sperm is adequate (on semen analysis), the eggs are okay (based on Age, FSH, and AMH levels, and the Fallopian Tubes are open (on HSG), there are basically three treatment options available: oral medications with or without intrauterine insemination (IUI), injectable medications with or without IUI and treatment by in vitro fertilization (IVF). Each has nuances, but patients are expected to choose based on a simple description of the treatment and some statistics. But how does one choose? Typically, the initial decision is based on a mix of the likelihood of success and the risks of treatment, the greatest of which is a multiple pregnancy and its attendant risk, the possibility of premature delivery. Cost, always a consideration for patients, factors into the decision analysis, but may not affect a doctor’s recommendation, which is typically based on the medical data.

Historically, patients with unexplained infertility would take a step-wise treatment algorithm, starting first with the simplest treatment (oral medications) and after a trial period move up to injectable hormones and insemination, finally stepping up to IVF treatment if unsuccessful. Modern treatment, however, has altered this approach.

Achieving a healthy singleton pregnancy in an efficient and cost-effective manner is the aim of infertility treatment. The FASTT study (2010) compared patients with unexplained infertility and randomized them to injectable hormones and insemination or IVF treatment after they had completed up to three cycles or oral medications and insemination. Essentially, one group of patients got to “skip” a step, moving from the simplest treatments directly to the most advanced treatment. Surprisingly, treatment by injectable medications was not much better than oral medications (7.6% vs. 9.8% per cycle), but IVF was a marked step up (30.7%). When compared, patients who followed the “accelerated” path, skipping the middle step, achieved pregnancy sooner and more cost-effectively than the traditional step-wise approach.

The reason for the failure of the middle step to markedly improve treatment success is difficult to ascertain, and that difficulty lies in the limited diagnostic tests that are available to assess fertility. It is possible that in a portion of these patients, infertility is characterized by a problem at the egg-sperm interaction that can only be overcome by direct laboratory intervention. Although injectable hormones may make more eggs available for fertilization than oral medications, the shared similarity with the simpler treatment means that in some cases, no real change in treatment has occurred. In fact, injectable medications carry with them an increased chance of twins, triplets, and beyond.

There are times when a step-wise approach may still make the most sense for patients with unexplained infertility, but a gradual increase in treatment intensity may unnecessarily draw out the treatment phase and at ultimately increased expense. Reproductive medicine has evolved over the past several decades. No longer is it standard to spend months on low tech ineffective treatment, when high tech treatment, such as IVF with selection of a single normal healthy embryo can lead to rapid success and healthy babies. Since many patients stop treatment out of frustration, taking the most efficient path will lead to more successful pregnancies.

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