Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome. (FSH)

July 3, 2016 updated by: AbdelGany Hassan, Cairo University

Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome: A Randomised Controlled Trial

210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive FSH, group 2 will have Letrozole and group 3 will act as the control group with no intervention.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age, with an incidence of 5 -10%. Classically clomiphene citrate (CC) is the first approach to induce ovulation in patients with PCOS. Although 70-80% of PCOS women can ovulate by the treatment with CC, only 40%of the PCOS women become pregnant. Women who do not ovulate with increasing doses of CC are described as being CC-resistant and remain a major challenge in gynecologic endocrinology. Traditional alternatives for CC-resistant patients include gonadotropin therapy and laparoscopic ovarian diathermy.

Gonadotropin therapy is widely used for ovulation induction in CC-resistant PCOS patients. The use of purified FSH preparation virtually free of LH activity, is a recommendable treatment since there is evidence that pure FSH may significantly reduce tonic LH levels, favourably alter the intraovarian hormonal milieu, and promote the initial follicular development with minimal risk of multiple follicular growth or ovarian hyperstimulation.

The use of metformin in PCOS is associated with cycle regulation, improved ovulation, and a reduction in circulating androgen levels. Metformin likely plays its role in improving ovulation induction in women with PCOS through a variety of actions, including reducing insulin levels and altering the effect of insulin on ovarian androgen biosynthesis, theca cell proliferation, and endometrial growth. In addition, potentially through a direct effect, it inhibits ovarian gluconeogenesis and thus reduces ovarian androgen production.

Letrozole is an orally-active aromatase inhibitor, with good potential for ovulation induction. Letrozole acts by reducing estrogen production by blocking androgens to estrogens conversion. Additionally, it has no adverse effect on endometrium and cervical mucus (7). This releases the pituitary from negative feedback of estrogens and releases FSH. Also, an added positive effect is increased follicular sensitivity to FSH through amplification of FSH receptor gene expression.

Hyper-insulinemia, which is closely associated with PCOS, is thought to be one of the causative factors for CC resistance. The prevalence of insulin resistance in PCOS is close to 50%.

All women with clomiphene resistant PCOS attending the subfertility clinic of Cairo university hospitals will be invited to participate in the study. PCOS diagnosis will be based on chronic anovulation and sonographic picture of polycystic ovaries (10). Clomiphene resistance will be defined as failure of ovulation in spite of receiving 150mg of clomiphene citrate for 5 days during the menstrual cycle.

Exclusion criteria are age >40 years, other causes of infertility, hperprolactinaemia, allergy to FSH or metformin, previous FSH or LOD therapy, and body mass index (BMI)>35.

The study will be explained to all the participants and a written informed consent will be obtained before participation.

Full history will be taken followed by complete examination and sonographic evaluation. Sonographic picture of polycystic ovaries will be defined when there are at least 12 follicles 2-9mm in the ovary and/or ovarian volume>10cm3 (10) 210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive FSH, group 2 will have Letrozole and group 3 will act as the control group with no intervention.

Group 1 will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days. The cycle will be cancelled if no follicles exceed 9mm 4 weeks after starting FSH. Group 2 will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding.

Group 3 will have regular progesterone withdrawal bleeding in the form of norethisterone (stereonate® Hi Pharm, Egypt).

Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the frequency of monitoring will be individualized according to the women's response. When the dominant follicle reaches 17mm or more women will receive Human chorionic gonadotrophin (Choriomon® IBSA, Switzerland) 5000IU and a timed intercourse will be advised 36 hours later.

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 3

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
      • BeniSuef, Egypt
        • BeniSuef University hospitals
      • Cairo, Egypt
        • Cairo University Hospitals

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:

  • Clomiphene resistant PCOS.

Exclusion Criteria:

  • Other causes of infertility.
  • Hyperprolactinaemia.
  • Allergy to Letrozole or FSH.

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: FSH
70 women will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9 mm the dose will be increased by 37.5 IU every 7 days.
Drug: FSH
75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days
Active Comparator: Letrozole
70 women will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding.
Drug: Letrozole
70 women will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ovulation
Time Frame: 6 weeks after starting the intervention
Regular vaginal ultrasounds will be done starting from the 8th day of starting the drug.
6 weeks after starting the intervention

Secondary Outcome Measures

Outcome Measure
Time Frame
Pregnancy
Time Frame: 6 months after starting the intervention
6 months after starting the intervention

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

May 1, 2013

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

November 26, 2014

First Submitted That Met QC Criteria

November 28, 2014

First Posted (Estimate)

December 1, 2014

Study Record Updates

Last Update Posted (Estimate)

July 6, 2016

Last Update Submitted That Met QC Criteria

July 3, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sub 6

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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