Comparison Between Letrozole and Laparoscopic Ovarian Drilling in Women With Clomiphene Resistant Polycystic Ovarian Syndrome (PCOS)

July 28, 2016 updated by: AbdelGany Hassan, Cairo University
140 women with clomiphene resistant PCOS will be randomly divided into 2 equal groups using computer generated random numbers. Group 1 will receive Letrozole, group 2 will have laparoscopic ovarian drilling (LOD).

Study Overview

Status

Unknown

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.

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 (4). 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.

Laparoscopic ovarian drilling (LOD) can avoid or reduce the need for gonadotropins for ovulation induction. Several potential mechanisms of action of LOD have also been suggested. The reduction of inhibin production following LOD is followed by an increase in FSH secretion and recruitment of a new cohort of follicles. Other theory is restoration of normal production of the putative gonadotropin surge after laparoscopic ovarian electrocautery. Moreover, drainage of androgens and inhibin from follicles surface may inhibit the excessive collagenisation of overlying ovarian cortex and facilitate Softening of ovarian tunica. Neighbouring follicles that are not undergoing atresia may then mature and gain access to the ovarian surface, facilitating ovulation. Initiation of normal inhibin B pulsatility by LOD appears to correlate with the postoperative onset of ovulatory cycles.

The main drawbacks of LOD are adhesions formation and ovarian atrophy. That is why minimising the number of diathermy points and avoiding diathermy near the ovarian hilum are recommended.

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. Clomiphene resistance will be defined as failure of ovulation in spite of receiving 150mg of clomiphene citrate for 5 days starting from the 3rd-5th day of the menstrual cycle.

Exclusion criteria are age >40 years, other causes of infertility, hyperprolactinaemia, previous Letrozole 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 140 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive Letrozole, group 2 will have LOD and group 3 will act as the control group with no intervention.

Group 1 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 2 will have LOD in which the ovaries will be stabilised by grasping the ovarian ligament and monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures will be individualised according to the size of the ovary.

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 (Anticipated)

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
        • Recruiting
        • BeniSuef University hospitals
      • Cairo, Egypt
        • Recruiting
        • 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 women

Exclusion Criteria:

  • Other causes of infertility.
  • Hyperprolactinaemia.
  • BMI>35.
  • Previous Letrozole or LOD therapy.

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: 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
Active Comparator: Ovarian drilling
70 women will have LOD in which the ovaries will be stabilised by grasping the ovarian ligament and monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures will be individualised according to the size of the ovary.
Procedure: Laparoscopic ovarian drilling

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 at regular intervals starting from the 10th day after the intervention
6 weeks after starting the intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pregnancy
Time Frame: 6 months after starting the intervention
Pregnancy will be diagnosed by the presence of an intra uterine gestational sac during vaginal ultrasound examination one week after a missed period.
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

November 1, 2014

Primary Completion (Anticipated)

May 1, 2017

Study Registration Dates

First Submitted

November 26, 2014

First Submitted That Met QC Criteria

November 28, 2014

First Posted (Estimate)

December 3, 2014

Study Record Updates

Last Update Posted (Estimate)

July 29, 2016

Last Update Submitted That Met QC Criteria

July 28, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sub 7

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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