LOS ANGELES — New data from two pilot studies support the use of aromatase inhibitors to promote pregnancy in women with ovulatory dysfunction or unexplained infertility, according to poster presentations at the annual meeting of the Society for Gynecologic Investigation.
In the first randomized study to test anastrozole as an infertility treatment, women who took the aromatase inhibitor before undergoing intrauterine insemination (IUI) had a pregnancy rate comparable overall with those undergoing standard treatment with clomiphene and IUI. Anastrozole cycles appeared to offer an advantage, however, in that they led to more pregnancies in women with polycystic ovary syndrome and generated three times fewer follicles overall.
In the second study, women taking letrozole before undergoing in vitro fertilization (IVF) produced more oocytes and had higher pregnancy rates than those who were treated with a standard protocol of gonadotropins, although the differences between groups were not statistically significant. This study was a randomized feasibility trial in low responders who had failed previous treatments and were scheduled for an aggressive IVF protocol.
Christopher S. Sipe, M.D., lead investigator of the anastrozole study, said in an interview that he believes enough data exist for physicians to start prescribing aromatase inhibitors for infertility patients, but that few will without an indication for infertility from the Food and Drug Administration. “I think you can still use it, but I don't think a lot of people will with the medicolegal aspects in the field,” said Dr. Sipe of the department of ob.gyn. at the University of Iowa Hospitals and Clinics, Iowa City.
The anastrozole trial recruited 50 couples from the University of Iowa Infertility Treatment Center. Patients with tubal factor infertility or severe male factor infertility were excluded.
Women were randomized to receive 1 mg of anastrozole or 100 mg of clomiphene citrate on cycle days 3 through 7. All women received intramuscular injections of 75 IU of purified FSH on days 7 through 11.
On day 12, ultrasounds and measurements of serum estradiol were initiated and performed every other day. If needed, FSH injections continued until a follicle greater than 18 mm was observed and the patient received 10,000 U of human chorionic gonadotropin. IUI followed 36 hours later.
Overall, the cancellation rate was 16% and the pregnancy rate 18% with nine pregnancies achieved. Though the pregnancy rates of 16% with anastrazole and 20% with clomiphene were similar, Dr. Sipe said the trial was too small to draw conclusions.
Serum estradiol was lower with anastrazole, and the investigators proposed that the smaller number of follicles in those patients suggests the aromatase inhibitor could produce fewer multiple births. “This study did not have enough patients to look at the multiple pregnancy rate—you need 1,200 patients or so—but that is what we are thinking,” Dr. Sipe said.
Perhaps the most provocative finding was in women with polycystic ovary syndrome. Anastrozole produced three pregnancies in this group, but clomiphene produced only one. A published study has also found these patients benefitted from letrozole (Fertil. Steril. 2001;75:305–9), so Dr. Sipe said the Iowa investigators plan further studies with anastrozole in this population.
Sonya Kashyap, M.D., worked on the letrozole study presented at the meeting while she was a fellow at the Cornell Center for Reproductive Medicine and Infertility, New York. Her group was able to randomize 55 patients, of whom 48 completed and were eligible for evaluation, according to Dr. Kashyap, now at the University of Ottawa.
The patients willing to enter the study were largely older couples who had nearly exhausted their options. Most fulfilled at least three of five entry criteria, only one of which was required for eligibility.
The study was not blinded but randomized patients by “concealment of allocation” to either a standard protocol of gonadotropins or letrozole before IVF. Physicians did not know which group patients would be in, and Dr. Kashyap maintained in an interview that the outcomes measured protected the study from bias once treatment began.
The final sample was small (26 women on the standard regimen and 22 on letrozole), and the primary outcome data were not statistically significant but trended in favor of the aromatase inhibitor. Compared with the control group, patients treated with letrozole had higher pregnancy rates per cycle started (3/22 vs. 1/26), per retrieval (3/14 vs. 1/16), and per transfer (3/13 vs. 1/14).