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

Phase 2

Completed

• Conditions: Infertility
• Interventions: Drug: Clomiphene citrate regimen; Drug: Extended letrozole regimen

• Registration Number: NCT01232075
• Lead Sponsor: Cairo University

Brief Summary

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 .

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 Timeline

• Study Start: 2008-09
• Primary Completion: 2010-11
• Study First Submitted: 2010-11-01
• Study First Submitted QC: 2010-11-01
• Study First Posted: 2010-11-02
• Study Completion: 2010-12
• Status Verified: 2011-07
• Last Update Submitted: 2011-07-11
• Last Update Posted: 2011-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 214

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clomiphene citrate regimen	Clomiphene citrate regimen	-
Extended letrozole regimen	Extended letrozole regimen	-

Primary Outcome Measures

Name	Time	Method
Clinical pregnancy rate	5 weeks after intrauterine insemination	Presence of intrauterine gestational sac detected by transvaginal ultrasound

Secondary Outcome Measures

Name	Time	Method
Ongoing Pregnancy Rate	18 weeks after intrauterine insemination	Pregnancies continued beyond 20 weeks gestation

Trial Locations

Locations (2)

Ahmed Elgazzar hospital; 🇪🇬 Cairo, Egypt

Cairo university hospital; 🇪🇬 Cairo, Egypt