Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS

September 30, 2015 updated by: Ghada Abdel Fattah, Cairo University

Combined Letrozole-metformin-pioglitazone Versus Combined Clomiphene Citrate-metformin-pioglitazone in Clomiphene Citrate-resistant Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the American College of Obstetrics and Gynecology (ACOG) recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC may be associated with poor endometrial thickening due to its antiestrogenic effect. Letrozole may improve this condition. In this study we will compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the ACOG recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates. There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogenic effects of CC. recent studies have suggested that letrozole, an aromatase inhibitor, does not possess the adverse antiestrogenic effects of CC and is associated with higher pregnancy rates than CC treatment in patients with PCOS.

In this study we shall compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.This will be a prospective comparative clinical trial in which 2 groups of women will be generated (groups A and B) using the sealed envelopes randomization method.Group A (40 women) will receive: letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Group B (40 women) will receive clomiphene citrate 100 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Cairo University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 20-40 years old
  • PCOS infertile women resistant to CC for3 cycles

Exclusion Criteria:

  • presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction.
  • use of gonadotropins before
  • previous ovarian drilling
  • presence of urinary symptoms especially bloody urine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: arm 1:letrozole-pioglitazone -metformin group
Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
Drug: induction of ovulation using letrozole-pioglitazone-metformin
induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
Radiation: transvaginal ultrasound
transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle
Other: body mass index (BMI) calculation
BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared
Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone
baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.
Other: pretreatment blood urea and serum creatinine
blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.
Other: serum estradiol (E2) on day 12
serum E2 will be assayed on day 12 of the cycle for all women.
Other: serum progesterone on day 21
serum progesterone will be assayed on day 21 for all women to monitor ovulation.
Other: blood urea and serum creatinine every month
blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions
ACTIVE_COMPARATOR: arm 2: clomiphene citrate-pioglitazone-metformin
Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
Radiation: transvaginal ultrasound
transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle
Other: body mass index (BMI) calculation
BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared
Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone
baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.
Other: pretreatment blood urea and serum creatinine
blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.
Other: serum estradiol (E2) on day 12
serum E2 will be assayed on day 12 of the cycle for all women.
Other: serum progesterone on day 21
serum progesterone will be assayed on day 21 for all women to monitor ovulation.
Other: blood urea and serum creatinine every month
blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions
Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin
induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Ovulation Rate
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Follicles>18mm.
Time Frame: 3 months
3 months
Endometrial Thickness
Time Frame: 3 months
3 months
Pregnancy Rate
Time Frame: 3 months
3 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of Pioglitazone as Regards Serum Creatinine
Time Frame: 3 months
serum creatinine was measured at the end of the study period (after 3 months) in both groups.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (ACTUAL)

February 1, 2014

Study Completion (ACTUAL)

April 1, 2014

Study Registration Dates

First Submitted

July 15, 2013

First Submitted That Met QC Criteria

July 24, 2013

First Posted (ESTIMATE)

July 26, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

October 20, 2015

Last Update Submitted That Met QC Criteria

September 30, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • fem2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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