As we end 2016, I wanted to review two landmark trials which have really changed the way we practice reproductive medicine. An explanation of both trials will give you a better understanding of why we choose different treatment options for patients and the evidence which supports such choices.
In 2010, the “Fast Track and Standard Treatment” Trial (FASTT) (Fertil Steril 2010; 94:888-99) studied the best course of treatment in women with unexplained infertility. The study included over 500 women who were between 21 and 39 years old with unexplained infertility. For one arm of the study, patients did “conventional treatment” which involved three cycles of clomiphene citrate (CC) with intrauterine insemination (IUI), followed by three cycles of gonadotropins (GN) with IUI followed by up to six cycles of in vitro fertilization (IVF). The “accelerated” arm did three cycles of CC/IUI followed by up to six cycles of IVF – skipping the gonadotropin treatment all together. Pregnancy rates were 8.5% with CC/IUI, 11.4% with GN/IUI, and 38.6% with IVF. However, while we often measure pregnancy rate for success, we also measure “take home baby rates” in discussing live birth rates. Live Birth rate (live births plus ongoing pregnancies >20 weeks) during the trial were on average 7.8% in CC/IUI cycles, 9.8% in GN/IUI cycles, and 30.7% in IVF cycles. Overall little loss rate in this under 40 population.
While some patients still may have an indication to pursue gonadotropin therapy, it has become less used mainly because of the extremely high chances of multiples. On average, gonadotropin/IUI treatment results in about 30-35% chance of twins and 3-5% chance of more than twins (multiples). This is unacceptably high for standard treatment.
The study found that in the accelerated arm of treatment, there were more pregnancies, time to pregnancy was reduced, and people spent less money.
Luckily, most of our patients have insurance for treatment, but for those that are self-pay for treatment, this is important. Most patients think of IVF being much more expensive, but this study found that it actually saved money because they did less treatment that was actually more effective. The patients saved an average of $2600 in the accelerated arm. Average time to pregnancy was three months less in the accelerated arm with mean time to pregnancy being eight months in the accelerated arm and eleven months in the conventional arm.
Because of this landmark study, many of us choose to advise patients who have unexplained infertility and who are less than age 40 to pursue conservative treatment with CC/IUI for three cycles followed by IVF. A large percentage of our patients are ready to expand their family around the age of 40. Even with our incredible technology, age plays an important role on aneuploidy and success rates in women pursuing pregnancy. Then the question was raised, how about women age 40 and older?
A follow-up trial, “The Forty and Over Treatment” Trial (FORT-T) (Fertil Steril 2014; 101(6);1574-1581) was done to answer this question. Approximately 150 women aged 38-42 were randomized to either CC/IUI, GN/IUI, or IVF. If the patients undergoing IUI cycles were not pregnant after two cycles, they would proceed with IVF. Pregnancy rates were 6.9% with CC/IUI, 7.7% with GN/IUI, and 24.7% with IVF. Live Birth rates during the trial were 3.4% in CC/IUI cycles, 6.6% in GN/IUI cycles, and 15.3% in IVF cycles. Higher loss rates correlate to the older patient age and expected increase in spontaneous loss and aneuploidy. Time to pregnancy in this study was decreased in the patients who went directly to IVF. It was approximately 12.2 months in the CC and GN arms and decreased to 8.7 in the IVF arm.
Since pursuing timely treatment is important in this age group (38 and older), it was concluded that women 38 and older should consider going right to IVF.
One interesting fact to note is that the success rates from the FASTT trial with IVF were only 30%. In our labs today, in good prognosis patients the rates are more than twice that amount. This shows how fast our technology is changing and how much our success rates have increased in the last 10 years. The main points of treatment choices, however, are unchanged by the age of the data. Our IVF technology has gotten so successful that for many patients IVF is the treatment of choice.
Individualizing care is really important in these cases. I find it important to review the data and the expected results with each patient and allow them to participate in the direction of their care. This is where we are able to guide patients and really work together with them as a team. We want to help patients be as successful as possible, while minimizing risks such as multiples. As we move into 2017, exciting upcoming technologic advances take us even further down a road of healthier pregnancies and more success!