Extended Letrozole Regimen Versus Clomiphene Citrate for Superovulation in Patients With Unexplained Infertility Undergoing Intrauterine Insemination

July 11, 2011 updated by: Cairo University
The aim of this randomized controlled trial is to compare the efficacy of extended letrozole regimen (2.5mg/day from cycle day 1 to 9) with clomiphene citrate (100 mg/day from cycle day 3 to 7) in women with unexplained infertility undergoing superovulation and intrauterine insemination .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Unexplained infertility is one of the most frequent infertility diagnoses encountered by the gynaecologists . Several studies reported that 10 to 20% of infertile couples have unexplained infertility .

Superovulation and intrauterine insemination (IUI) is an effective treatment for couples with unexplained infertility . Superovulation increases the probability of pregnancy by increasing the number of oocytes suitable for fertilization or by correcting any subtle defect in ovulation . Furthermore, IUI increases the concentration of active motile sperms reaching the fallopian tube and overcomes male factors or cervical factors of infertility not detected by conventional tests .

For more than four decades , clomiphene citrate has been the first line therapy used for induction of ovulation in women with anovulatory infertility and for superovulation in couples with unexplained infertility, mild endometriosis and mild male factor of infertility . Clomiphene citrate is cheap , orally administered , requires no frequent monitoring and associated with very low risk of high-order multiple gestation and severe ovarian hyperstimulation syndrome . However , clomiphene citrate causes long lasting depletion of estrogen receptors and therefore exerts antiestrogenic effect on estrogen target tissues as endocervical mucosa and endometrium .Several studies revealed the clomiphene citrate has a deleterious effect on cervical mucous quantity and quality and endometrial development resulting in endometrial thinning , luteal phase defect ,decreased uterine flow and implantation failure .

During the past decade, letrozole (aromatase inhibitor approved by FDA for the treatment of postmenopausal women with breast cancer ) has been successfully used in induction of ovulation in anovulatory patients with polycystic ovary syndrome and in augmentation of ovulation in ovulatory women . In contrast to clomiphene citrate , letrozole is rapidly eliminated from the body and does not deplete estrogen receptors and therefore has no antiestrogenic effects on endometrium or endocervical mucosa .

Several studies revealed that letrozole can be used as an alternative to clomiphene citrate for superovulation in patients with unexplained infertility . A metaanalysis of seven randomized controlled trials comparing aromatase inhibitors ( letrozole or anastrozole ) with clomiphene citrate in patients with unexplained infertility revealed that the pregnancy rate was comparable between both management options .

The optimal dose and duration of letrozole administration for superovulation in patients with unexplained infertility is still not clear. In various studies reporting the use of letrozole for the superovulation , letrozole was administrated from cycle 3 to 7 with daily dose ranging from 2.5 to 7.5 mg .In a randomized controlled trial , AI-Fadhli et al reported that the pregnancy rate was significantly higher in patients with unexplained infertility treated with 5 mg compared to those treated with 2.5 mg . On the other hand, a randomized controlled trial comparing three doses of letrozole (2.5,5,7.5 mg/day)in the management of patients with unexplained infertility revealed that the pregnancy rates were comparable between the three groups .

The aim of this randomized controlled trial is to compare the efficacy of extended letrozole regimen (2.5mg/day from cycle day 1 to 9) with clomiphene citrate (100 mg/day from cycle day 3 to 7) in women with unexplained infertility undergoing superovulation and intrauterine insemination .

Study Type

Interventional

Enrollment (Actual)

214

Phase

  • Phase 2

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 Hospital
      • Cairo, Egypt
        • Ahmed Elgazzar hospital

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

14 years to 33 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patients with unexplained infertility
  • Age between 18 - 37 years
  • Period of infertility > 1 year
  • Patent Fallopian tubes detected by hysterosalpingography and/or laparoscopy
  • Normal basal luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin concentrations
  • Normal recent semen analysis (according to World Health Organization criteria)

Exclusion Criteria:

  • FSH> 10 IU/L
  • Irregular menstrual cycles
  • Polycystic ovary syndrome
  • Endometriosis
  • Endocrinologic disorders
  • Systemic disease contraindicating pregnancy
  • Previous IUI cycles
  • liver or kidney diseases

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Extended letrozole regimen
Drug: Extended letrozole regimen

Letrozole (Femara; Novartis pharma AG, Basle, Switzerland) 2.5mg /day is administered from cycle day 1 to 9 .

Human chorionic gonadotropin (Pregnyl; N.V. Organon, Oss, Holland) ( 10.000 IU/I.M ) is administered to trigger ovulation when at least one follicle measures more than 18mm in mean diameter .Intrauterine insemination is performed 36 - 40 hours after HCG injection .

Starting from cycle day 9 , ultrasound scans are repeated daily to monitor follicle growth . Serum estradiol and endometrial thickness are measured on the day of HCG administration.

Serum B-subunit HCG is measured 2 weeks after IUI to diagnose pregnancy .

Other Names:
  • letrozole 2.5mg/day from cycle day 1 to 9
Active Comparator: Clomiphene citrate regimen
Drug: Clomiphene citrate regimen

Clomiphene citrate(Clomid; Aventis pharma S.AE, Global Napi pharmaceuticals, Cairo, Egypt) 100 mg/day is administered from cycle day 3 to 7.

Human chorionic gonadotropin (Pregnyl; N.V. Organon, Oss, Holland) ( 10.000 IU/I.M ) is administered to trigger ovulation when at least one follicle measures more than 18mm in mean diameter .Intrauterine insemination is performed 36 - 40 hours after HCG injection .

Starting from cycle day 9 , ultrasound scans are repeated daily to monitor follicle growth . Serum estradiol and endometrial thickness are measured on the day of HCG administration.

Serum B-subunit HCG is measured 2 weeks after IUI to diagnose pregnancy .

Other Names:
  • Clomiphene citrate 100mg/day from cycle day 3 to 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: 5 weeks after intrauterine insemination
Presence of intrauterine gestational sac detected by transvaginal ultrasound
5 weeks after intrauterine insemination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing Pregnancy Rate
Time Frame: 18 weeks after intrauterine insemination
Pregnancies continued beyond 20 weeks gestation
18 weeks after intrauterine insemination

Collaborators and Investigators

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

Sponsor

Cairo University

Collaborators

Ahmed Elgazzar Hospital

Investigators

  • Study Chair: Usama M Fouda, M.D, PhD, Cairo university
  • Study Director: Ahmed M Sayed, M.D, PhD, 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

September 1, 2008

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

November 1, 2010

First Submitted That Met QC Criteria

November 1, 2010

First Posted (Estimate)

November 2, 2010

Study Record Updates

Last Update Posted (Estimate)

July 12, 2011

Last Update Submitted That Met QC Criteria

July 11, 2011

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • clomid/extended letr/unexp.inf

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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