A move from clomiphene directly to IVF may cut time to pregnancy
Reindollar RH, Regan MM, Neumann PJ, Thornton KL, Alper MM, Goldman MB. A randomized controlled trial of 503 couples assigned to conventional infertility treatment or an accelerated track to IVF: Preliminary results of the fast track and standard treatment (FASTT) trial. Fertil Steril. 2007;88(Suppl 1):S41.
This very important abstract, presented at the annual meeting of ASRM, has the potential to dramatically change fertility treatment. The multicenter randomized controlled clinical trial measured the efficacy and time to pregnancy of an accelerated treatment strategy for women 21 to 39 years old who had unexplained infertility. A similar percentage of patients—approximately 75%—became pregnant in each arm (traditional versus accelerated), with a shorter time to pregnancy in the accelerated arm.
The new paradigm for management of unexplained infertility includes:
- comprehensive fertility history and physical examination
- targeted laboratory testing and other investigation, as needed
- counseling and psychological support for the patient once the diagnosis is made
- empiric treatment with clomiphene citrate plus intrauterine insemination (IUI) for as many as three cycles
- immediate IVF for as many as six cycles.
Details of the trial
Women in the trial had attempted to conceive for 12 months and had normal ovarian reserve (and semen analysis) and no pelvic pathology. Couples already treated for infertility were excluded.
Participants were randomized to:
- a conventional treatment regimen of three cycles of clomiphene citrate with IUI, three cycles of folliclestimulating hormone (FSH) and IUI, and as many as six cycles of IVF or
- three cycles of clomiphene citrate with IUI and then as many as six cycles of IVF.
Regimen likely reduces cost, stress
Major issues affecting the eventual success rate for infertile couples are cost and psychological stress, which can cause even patients who have a good prognosis to drop out of treatment. The major complication of fertility treatment is multiple pregnancy. By avoiding the use of gonadotropins in couples with unexplained infertility and accelerating the transition to IVF, physicians can lower the cost and psychological stress of treatment. They can also reduce the likelihood of multiple pregnancy because it is easier to control the number of embryos transferred in IVF than the number of follicles that develop with gonadotropins.
In women younger than 35 years on the first IVF cycle who have a good prognosis, ASRM now recommends that only one or two day-3 embryos be transferred, and not more than one day-5 blastocyst.4 The multiple-birth rate has declined in recent years, as more and more IVF clinics place fewer embryos; the rate should continue to fall with wider application of elective single-embryo transfer.5,6
Because this accelerated protocol produces a similar number of births over a shorter period and has the potential to lower cost, psychological stress, and the multiple-birth rate, it deserves implementation for many patients and warrants further evaluation for potential benefits in other populations.
It’s no help, after all: Preimplantation genetic screening for aneuploidy
Practice Committee of the Society for Assisted Reproductive Technology and Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: A Practice Committee report. Fertil Steril. 2007;88:1497–1504.
Mastenbroek S, Twisk M, van Echten-Arends J, et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:9–17.
Preimplantation genetic diagnosis of known single-gene defects, structural chromosomal rearrangements, X-linked disorders, and human leukocyte antigen typing is a major benefit to couples known to be at risk of passing on a heritable and debilitating genetic disease. Aneuploidy is the most common cause of early pregnancy loss, and its prevalence increases with maternal age and may increase in chromosomally normal couples who experience recurrent early pregnancy loss or repeated failure of IVF cycles. Preimplantation genetic screening (PGS) has been advocated to identify and transfer only euploid embryos and increase the chance of successful pregnancy.
New data from Mastenbroek and colleagues indicate that PGS for aneuploidy does not increase the rate of pregnancy or live birth. After several years of increasing utilization and studies suggesting that PGS has benefit, the first multicenter, randomized, doubleblind, controlled study that compared three cycles of IVF with and without PGS in women 35 to 41 years old concluded that PGS does not increase but, in fact, significantly reduces the rate of pregnancy and live birth in this group.