AMIGOS Study Available to Patients With Unexplained Infertility

Couples with infertility usually go through several studies to determine if there is a cause for their inability to achieve a pregnancy. The male partner’s semen is tested for the number, appearance and motility of the sperm. The woman’s blood is tested and a vaginal ultrasound performed, both to evaluate egg quality and quantity.

The woman is also tested for anatomic conditions such uterine abnormalities and blockage of the fallopian tubes. If all of the tests turn out to be normal, however, the couple are said to have “unexplained infertility.”

Having no clear diagnosis is a double-edged sword: The couple and their doctor are relieved that there is no specific abnormality, but are concerned because the couple is not getting pregnant.

If unexplained infertility is diagnosed, fertility specialists usually recommend “empiric therapy,” which usually means the progressive use of fertility drugs to “superovulate” the woman. Superovulation means that the fertility drugs increase the number of eggs ovulated from one to two or more. Progressive means that the couple will be given the least expensive and least invasive medicines available, almost always an oral medication such as Clomiphene citrate (also called Clomid). In recent years, another medication called Letrozole may also be employed.

In addition to “superovulation,” most doctors will also use intrauterine insemination. This means that the partner’s sperm is washed and then placed high in the woman’s uterine cavity to be close to the fallopian tubes where the eggs will be waiting to be fertilized.

The combination of fertility drugs in the woman and placement of the man’s washed sperm high in the uterine cavity is felt to increase pregnancy rate from a baseline of 2% per menstrual cycle (the probable rate in a couple who have been trying to conceive for a year without success) to 10% (the likely success rate in couples undergoing superovulation with intrauterine insemination).

If the couple fails to conceive with a combination of the oral medication and intrauterine insemination, they may be offered injectable medicines called “gonadotropins.” Generally these medications are felt to be more aggressive than the oral medications, but may have a higher success rate. The fact that they “may” improve success rates has never been actually tested in a properly conducted, scientifically rigorous study.

The current “Assessment of Multiple Intrauterine Gestation from Ovarian Stimulation (AMIGOS)” trial at University of Colorado Advanced Reproductive Medicine seeks to remedy this situation. Sponsored by the National Institutes of Health and conducted by a multicenter group of fertility clinics, the trial will test over 900 couples, divided into three groups, to see which approach is the best as the first line treatment for patients with unexplained infertility.

Of the more than 20 centers that applied to be a center to conduct the study, the University of Colorado’s Advanced Reproductive Medicine Center was one of seven sites to be selected because of the expertise of its faculty and the resources available to conduct the study.

There are two pill arms in the study. Both of these are blinded, meaning that neither the investigator nor the patient know whether they are using the Clomiphene citrate or the Letrozole. The third arm of the study, which involves the use of injectable medicines, is not blinded because it is obviously impossible to mask the use of injections to patients and their doctors.

The patients are treated for a total of four cycles in all three arms of the study, and data is collected. Important outcomes that are measured include pregnancy outcome, complications, number of eggs recruited and multiple pregnancies such as twins and triplets. After all the data are collected, the investigators will publish the data and reveal which treatments were best in achieving pregnancy and which were safest.

The patients benefit by receiving free treatment cycles and are not harmed because all of the treatments are considered standard of care. The best news is that in less than two years, we will know which of the treatment protocols is best. Patients can then be counseled as to the most appropriate treatment for unexplained infertility.