Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility

Abstract

BACKGROUND-The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. METHODS-We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. RESULTS-After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P = 0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P = 0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P = 0.15) or clomiphene alone (8 of 85, 9%; P = 0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P = 0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. CONCLUSIONS-In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.

Dual Ovulation Triggering With Follicle-Stimulating Hormone and Human Chorionic Gonadotropin in Women With Unexplained Infertility Underwent Letrozole Superovulation and Intrauterine Insemination: A Randomized Controlled Trial.

“…The current study reported a clinical pregnancy rate of 25% and a live birth rate of 21.3% for the total letrozolestimulated cycles, regardless of the ovulation triggering protocol; the rates that accord with those formerly stated in various studies evaluated letrozole superovulation in women with UI (table 4) [11][12][13][14][15][16] . However, dual triggering by FSH/hCG compared to hCG alone improved the outcome of Letrozole-stimulated IUI cycles manifested as significantly higher pregnancy rate pre-cycle (12.5% vs. 5.8%: p=0.049) and per-woman (33.33% vs. 16.67%: p=0.049), and a significantly higher live birth rate (29.6% vs, 12.5%; p= 0.039).…”

“…However, dual triggering by FSH/hCG compared to hCG alone improved the outcome of Letrozole-stimulated IUI cycles manifested as significantly higher pregnancy rate pre-cycle (12.5% vs. 5.8%: p=0.049) and per-woman (33.33% vs. 16.67%: p=0.049), and a significantly higher live birth rate (29.6% vs, 12.5%; p= 0.039). The reported pregnancy and live birth rates in the FSH/hCG trigger group are superior to those reported in diverse studies evaluating different letrozole-stimulated IUI protocols in women with UI (table 4) [11][12][13][14][15][16] . To our knowledge, this is the first trial planned to appraise the effect of FSH/hCG dual triggering in letrozole-stimulated cycles in ladies with UI.…”

“…Secondary outcomes included the frequency of ovarian hyperstimulation syndrome (OHSS), multiple gestations, and abortion. Results: Significantly higher pregnancy rates pre-cycle (12.5% vs. 5.8%: p=0.049) and per-woman (33.33% vs. 16.67%: p=0.049) and live birth rate (29.6% vs. 12.5%; p= 0.039) were noted in the study group compared to the control group. Abortion occurred in 2 out of 18 pregnancies (11.11 %) in the study group and in 2 out of 9 pregnancies (22.22 %) in the control group with no significant difference.…”

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination

“…In couples with unexplained infertility undergoing IUI, where it has been shown that OS significantly increases LBR when compared to natural cycles [4,21] , only one study comparing CC and letrozole reported LBR as an outcome [22] . The Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) trial analyzed LBR as a secondary outcome and found rates with letrozole (18.7%) statistically noninferior to rates with CC (23.3%) [22] . Cumulative LBR seem to be higher with both treatments in our study, probably because the patients included had no history of infertility, and only cryopreserved donor sperm was used.…”

Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

“…cretion, which stimulates the ovaries, resulting in increased oestrogen levels. This effect is helpful in reproductive medicine [24]. For this reason, AIs are not suitable for endocrine therapy for breast cancer treatment in pre-menopausal women.…”