Combination Letrozole and Clomiphene Citrate Versus Letrozole Alone

NCT ID: NCT06507332

Last Updated: 2024-07-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2024-09-10

Brief Summary

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.

Detailed Description

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.

Other than letrozole or CC for ovulation induction, there are few treatment options available to PCOS patients except proceeding to gonadotropin injections or in vitro fertilization, both of which are associated with increased cost and risk.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5mg

Intervention Type: DRUG

to assess and compare the efficacy of Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome (PCOS)

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

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5mg

Intervention Type: DRUG

to assess and compare the efficacy of Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome (PCOS)

Interventions

Letrozole 2.5mg

to assess and compare the efficacy of Combination of letrozole and clomiphene citrate versus letrozole alone for ovulation induction in women with polycystic ovary syndrome (PCOS)

Intervention Type: DRUG

Other Intervention Names

Clomiphene Citrate

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Unexplained infertility.
• Other conditions that can cause chronic anovulation and androgen excess such as hyperthyroidism by thyroid profile.
• congenital adrenal hyperplasia
• Cushing
• 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)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: collaborator

Egymedicalpedia

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dina Yahia, Professor

Role: STUDY_CHAIR

Department of Obstetrics & Gynecology,Ain Shams University

Al Hassan Mohammad Khedr, Lecturer

Role: STUDY_DIRECTOR

Department of Obstetrics & Gynecology,Ain Shams University

Locations

Ain Shams University Hospitals

Cairo, Abbasia, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Mohamed Adel Mousa, MSC

Role: CONTACT

sedyyasedy@gmail.com

+201093429998

Facility Contacts

Mohamed Adel Mousa, Resident

Role: primary

sedyyasedy@gmail.com

+201093429998

Other Identifiers

Mohamed Adel Mousa

Identifier Type: -

Identifier Source: org_study_id