Combination Letrozole and Clomiphene Citrate Versus Letrozole Alone for Ovulation Induction in Women With Polycystic Ovary Syndrome: A Randomized Control Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Pregnancy Check
研究概览
简要总结
Clomiphene citrate is a non-steroidal triphenylethylene derivative distantly related to diethylstilbestrol. It acts as a selective estrogen receptor modulator (SERM), similar to tamoxifen and raloxifene. All three drugs are competitive inhibitors of estrogen binding to estrogen receptors (ERs) and have mixed agonist and antagonist activity, depending upon the target tissue.
Letrozole is a potent, nonsteroidal, aromatase inhibitor, originally used for postmenopausal breast cancer therapy.
详细描述
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women and the most common cause of anovulatory infertility. The treatment of infertility in patients with PCOS focuses on ovulation induction. Many treatment regimens have been used, with varying success, to achieve ovulation, pregnancy, and live birth.
Clomiphene citrate (CC) is a commonly prescribed pharmacologic agent used to induce ovulation in women with PCOS. It works as a selective estrogen receptor modulator by competitively attaching to nuclear estrogen receptors. As the negative feedback of estrogen is reduced, secretion of gonadotropin hormones increases, inducing ovarian follicular growth.
Clomiphene citrate (CC) also has an anti-estrogenic effect on endometrial development and cervical mucus production,which has been suggested to contribute to a relatively low pregnancy rate despite a high ovulation rate.
Letrozole is another commonly used oral ovulation induction agent, with a different mechanism of action. It works as a highly selective aromatase inhibitor, preventing androgen-to-estrogen conversion. One proposed mechanism is via suppressed estrogen production resulting in decreased negative feedback on the hypothalamus and increased secretion of Follicular Stimulating Hormone (FSH). An additional proposed mechanism of improved ovulatory rates with the use of letrozole is increased follicular sensitivity to FSH resulting from temporarily increased intraovarian androgens .
Letrozole may offer a benefit over CC for ovulation induction because it does not block estrogen receptors in both central and peripheral target tissues, and normal central feedback mechanisms remain intact. The Pregnancy and Polycystic Ovary Syndrome (PPCOS) trial, a randomized controlled trial comparing letrozole and CC, demonstrated that letrozole was associated with a higher live birth rate (27.5% vs. 19.1%; P=007; rate ratio 1.44, 95% confidence interval [CI] 1.10-1.87) and cumulative ovulation rate (61.7% vs. 48.3%; P<.001) among women with PCOS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of infertility, defined as the inability of couple to achieve a pregnancy after 12 months of regular timed unprotected intercourse in women <35 years of age or after 6 months in women >35 years of age.
- •Diagnosis of PCOS based on the Rotterdam criteria, including two of the following three findings: oligomenorrhea or chronic anovulation, hyperandrogenism (clinical or laboratory), and polycystic ovary(ies) on ultrasound .
- •Normal HSG
- •Normal semen analysis.
- •Has capacity to participate in the study.
排除标准
- •Unexplained infertility.
- •Other conditions that can cause chronic anovulation and androgen excess such as hyperthyroidism by thyroid profile.
- •congenital adrenal hyperplasia
- •Untreated hyperprolactinemia.
- •Medical conditions not well controlled or contraindicated to get pregnant with it like (uncontrolled diabetes mellitus, hypertension) .
- •endometrial hyperplasia/cancer
- •Allergy or contraindications to letrozole or CC. (by history)
研究组 & 干预措施
Group 1 (Letrozole group)
About 32 patients will receive letrozole 2.5 mg tablets only , once daily from the third date of the menses for 5 days for 3 successive periods
干预措施: Letrozole 2.5mg (Drug)
Group 2 (Letrozole and Clomiphene Citrate)
About 32 patients will receive combined letrozole 2.5 mg tablets once daily and clomiphene citrate 50 mg tablets once daily from the third date of the menses for 5 days for 3 successive periods
干预措施: Letrozole 2.5mg (Drug)
结局指标
主要结局
Pregnancy Check
时间窗: 2 weeks after ovulation
The participants required to make pregnancy test after Receiving the drugs of the study
次要结局
未报告次要终点