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Combined Letrozole and Clomid in Women With Infertility and PCOS

Primary Purpose

Polycystic Ovary Syndrome, Infertility

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Clomiphene

Letrozole

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Willing to comply with all study procedures and be available for the duration of the study
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
Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria
Ability to have regular intercourse during the ovulation induction phase of the study
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:

Current pregnancy
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
Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
Uncorrected thyroid disease
Untreated hyperprolactinemia.
Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension
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
Contraindications to letrozole: hypersensitivity to letrozole or any of its components.
Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month.
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).

Sites / Locations

University of Iowa Hospitals & Clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Letrozole

Letrozole + Clomiphene

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level

Ovulation: mid-luteal progesterone > /=3 ng/mL. No ovulation: mid-luteal progesterone <3ng/mL.

Secondary Outcome Measures

Number of Developing Follicles

Number of follicles measuring > 10mm on ultrasound

Size of Largest Developing Follicle

Size of largest follicle on ultrasound

Endometrial Thickness

Thickness of endometrial lining assessed by ultrasound

Conception

Conception: a positive serum or urinary test of hCG; No conception: Neither a positive serum or urinary test of hCG

Clinical Pregnancy

Clinical Pregnancy: an intrauterine pregnancy with fetal heart motion determined by ultrasonography; No Clinical Pregnancy: no intrauterine pregnancy with fetal heart motion determined by ultrasonography

Multiple Gestation

Multiple Gestation: an intrauterine pregnancy with multiple fetal heart rates determined by ultrasonography; No Multiple Gestation: either no intrauterine pregnancy, or an intrauterine pregnancy with a single fetal heart rate determined by ultrasonography

Live Birth

Live Birth: delivery of a live infant; No Live Birth: no delivery of a live infant

Pregnancy Loss

Pregnancy Loss: any pregnancy loss including biochemical pregnancy, ectopic pregnancy, and miscarriage; No Pregnancy Loss: no pregnancy loss including biochemical pregnancy, ectopic pregnancy, or miscarriage.

Full Information

NCT ID

NCT02802865

First Posted

June 9, 2016

Last Updated

September 25, 2019

Sponsor

Rachel Mejia

1. Study Identification

Unique Protocol Identification Number

NCT02802865

Brief Title

Combined Letrozole and Clomid in Women With Infertility and PCOS

Official Title

Combined Letrozole and Clomid in Polycystic Ovary Syndrome: a Randomized Control Trial of Combination of Letrozole and Clomiphene Citrate or Letrozole Alone for the Treatment of Infertility in Women With Polycystic Ovary Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

August 2016 (undefined)

Primary Completion Date

May 2018 (Actual)

Study Completion Date

February 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Rachel Mejia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Polycystic Ovary Syndrome, Infertility

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Letrozole

Arm Type

Active Comparator

Arm Description

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

Arm Title

Letrozole + Clomiphene

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Clomiphene

Other Intervention Name(s)

clomid, clomiphene citrate

Intervention Type

Drug

Intervention Name(s)

Letrozole

Other Intervention Name(s)

femara

Primary Outcome Measure Information:

Title

Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level

Description

Ovulation: mid-luteal progesterone > /=3 ng/mL. No ovulation: mid-luteal progesterone <3ng/mL.

Time Frame

7 days following LH surge or at cycle day 21 if no LH surge was detected

Secondary Outcome Measure Information:

Title

Number of Developing Follicles

Description

Number of follicles measuring > 10mm on ultrasound

Time Frame

Cycle day 12-14

Title

Size of Largest Developing Follicle

Description

Size of largest follicle on ultrasound

Time Frame

Cycle day 12-14

Title

Endometrial Thickness

Description

Thickness of endometrial lining assessed by ultrasound

Time Frame

Cycle day 12-14

Title

Conception

Description

Conception: a positive serum or urinary test of hCG; No conception: Neither a positive serum or urinary test of hCG

Time Frame

5 weeks after treatment

Title

Clinical Pregnancy

Description

Time Frame

6-7 weeks after treatment

Title

Multiple Gestation

Description

Time Frame

9-10 months after treatment

Title

Live Birth

Description

Live Birth: delivery of a live infant; No Live Birth: no delivery of a live infant

Time Frame

9-10 months after treatment

Title

Pregnancy Loss

Description

Time Frame

9-10 months after treatment

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing to comply with all study procedures and be available for the duration of the study 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 Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria Ability to have regular intercourse during the ovulation induction phase of the study 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: Current pregnancy 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 Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities Uncorrected thyroid disease Untreated hyperprolactinemia. Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension 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 Contraindications to letrozole: hypersensitivity to letrozole or any of its components. Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month. 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rachel Mejia, DO

Organizational Affiliation

University of Iowa Hosptials & Clinics

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Brad Van Voorhis, MD

Organizational Affiliation

University of Iowa Hospitals & Clinics

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Iowa Hospitals & Clinics

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30683591

Citation

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.

Results Reference

derived

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Combined Letrozole and Clomid in Women With Infertility and PCOS

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