Combined Letrozole and Clomid in Women With Infertility and PCOS

NCT ID: NCT02802865

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2019-02-28

Brief Summary

This study evaluates the addition of clomid to letrozole for the treatment of infertility in women with polycystic ovary syndrome. Half of the participants will receive letrozole and clomid in combination, while the other half will receive letrozole alone.

Detailed Description

Letrozole and Clomid are both used for ovulation induction, but they have different mechanisms of action. Letrozole has been shown to be superior to clomid in achieving live birth rates in women with infertility and polycystic ovary syndrome. However, the combination of these medications has not been studied. This is a pilot study to evaluate if the combination treatment has improved efficacy as measured by ovulation rate.

This is a randomized controlled trial of letrozole versus letrozole and clomiphene citrate (CC) for one menstrual cycle. Women will be randomized in a 1:1 ratio to receive letrozole 2.5 mg or combination of letrozole 2.5 mg and clomiphene 50 mg for 5 days on days 3-7 of menstrual cycle. The women and their partners will be instructed to have regular intercourse with the intent to conceive during the cycle. Patients will have an transvaginal ultrasound mid cycle and to evaluate number of follicles (>15 mm), follicle size, endometrial thickness and pattern. Patients will have mid- luteal phase progesterone level drawn to evaluate ovulation. Side effect profile will also be monitored.

Conditions

Polycystic Ovary Syndrome; Infertility

Study Design

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

Study Groups

Letrozole

Letrozole 2.5 mg orally for 5 days on cycle days 3-7

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

Letrozole + Clomiphene

Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7

Group Type: EXPERIMENTAL

Clomiphene

Intervention Type: DRUG

Letrozole

Intervention Type: DRUG

Interventions

Clomiphene

Intervention Type: DRUG

Letrozole

Intervention Type: DRUG

Other Intervention Names

clomid; clomiphene citrate; femara

Eligibility Criteria

Inclusion Criteria

1. Willing to comply with all study procedures and be available for the duration of the study

2. Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular timed unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older

3. Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria

4. Ability to have regular intercourse during the ovulation induction phase of the study

5. Normal sperm concentration of 15 million/mL and with normal motility of > 40% according to World Health Organization cutoff points, in at least one ejaculate during the previous year

Exclusion Criteria

1. Current pregnancy

2. Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months

3. Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities

4. Uncorrected thyroid disease

5. Untreated hyperprolactinemia.

6. Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension

7. Contraindications to clomiphene citrate: hypersensitivity to CC or any of its components, history of liver disease or known liver disease, unknown cause of abnormal uterine bleeding, or intracranial lesion

8. Contraindications to letrozole: hypersensitivity to letrozole or any of its components.

9. Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month.

10. If patients are suspected based on clinical findings for other etiologies that mimic PCOS, work up must be completed to exclude other etiologies prior to enrollment (i.e. Cushing's syndrome, androgen-secreting tumor).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Rachel Mejia

OTHER

Sponsor Role: lead

Responsible Party

Rachel Mejia

Associate Fellow

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rachel Mejia, DO

Role: PRINCIPAL_INVESTIGATOR

University of Iowa Hosptials & Clinics

Brad Van Voorhis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa Hospitals & Clinics

Locations

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Countries

United States

References

Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2019 Mar;111(3):571-578.e1. doi: 10.1016/j.fertnstert.2018.11.030. Epub 2019 Jan 22.

Reference Type: DERIVED

PMID: 30683591 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201606806

Identifier Type: -

Identifier Source: org_study_id