A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome

Abstract

Objective: To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). Design: Open-label randomized controlled trial. Setting: Academic medical center using two clinic sites. Patient(s): Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. Interventions(s): Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle. Main Outcome Measure(s): Ovulation defined as mid-luteal serum progesterone concentration R3 ng/mL. Result(s): Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. Conclusion(s): The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate.

Simultaneous Letrozole and Clomiphene Citrate versus Letrozole Alone in Clomiphene Citrate Resistant Polycystic Ovary Syndrome: A Randomised Controlled Trial

“…In addition both CC and letrozole have a different mechanism of actions this makes letrozole a promising agent for treatment in those patients either alone or in combination with CC that may provide complementary effects. Although several studies compared the effect of letrozole and CC in PCOS, And few studies compared combination of letrozole and CC versus letrozole alone in PCOS [13] [14]. However no study compared between them in clomiphene-resistant PCOS (CCR-PCOS).…”

“…Justice et al, in 2013 studied the effect of simultaneous clomiphene citrate and letrozole therapy for ovulation induction in CCR-PCOS and concluded that it can be considered for ovulation induction in patients who are resistant to single-agent therapy prior to proceeding to gonadotropins therapy [20]. Also, Mejia et al [13] found a higher ovulation rate with simultaneous clomiphene citrate and letrozole therapy when compared with of letrozole alone (77% vs. 43%).…”

“…Several studies compared between letrozole and CC in PCOS, and few studies compared combination of letrozole and CC versus letrozole alone in PCOS [13] Open Journal of Obstetrics and Gynecology [14]. However no study compared between them in clomiphene-resistant PCOS (CCR-PCOS).…”

The synthesis and study of physicochemical properties of 1,2,4-triazole derivatives containing the phenethyl group in position 5

“…Основною перевагою сполук на основі вищезазначеного гетероциклу є те, що вони виявляють низькі показники гострої токсичності одночасно з широким спектром фармакологічної дії. На сьогодні вже створено велику кількість лікарських субстанцій, які містять структурний фрагмент 1,2,4-триазолу, а саме флуконазол [7], вориконазол [8], анастрозол [9], ітраконазол [10], летрозол [11]. Враховуючи вищезазначене пошук та створення нових молекул на основі 1,2,4-триазолу є актуальним завданням сучасної синтетичної та фармацевтичної хімії.…”

A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome

“…A single recently published pilot RCT, powered for the primary outcome measure of ovulation rate, compared letrozole with letrozole combined with clomiphene citrate over one treatment cycle in 70 infertile PCOS women with a mean BMI of 33–34 kg/m 2 of whom 81% had been treated with letrozole or clomiphene citrate in the past and 40% were currently taking metformin during the trial [27]. The results showed a higher ovulation rate with letrozole combined with clomiphene citrate compared to letrozole alone (77.1% versus 42.9%; RR 1.80; 95% CI 1.18–2.75; p = 0.007), but there was insufficient evidence for a difference in clinical pregnancy (2.9% versus 9.1%; RR 3.09; 95% CI 0.34– 28.23; p = 0.356) or live birth (7% versus 12%; RR 1.68; 95% CI 0.19–14.66; p = 1.00) rates between the two interventions.…”