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

This study has been completed.
Sponsor:
Collaborator:
Ahmed Elgazzar Hospital
Information provided by:
Cairo University
ClinicalTrials.gov Identifier:
NCT01232075
First received: November 1, 2010
Last updated: July 11, 2011
Last verified: July 2011
  Purpose

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 .


Condition Intervention Phase
Infertility
Drug: Extended letrozole regimen
Drug: Clomiphene citrate regimen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Extended Letrozole Regimen Versus Clomiphene Citrate for Superovulation in Patients With Unexplained Infertility Undergoing Intrauterine Insemination

Resource links provided by NLM:


Further study details as provided by Cairo University:

Primary Outcome Measures:
  • Clinical pregnancy rate [ Time Frame: 5 weeks after intrauterine insemination ] [ Designated as safety issue: No ]
    Presence of intrauterine gestational sac detected by transvaginal ultrasound


Secondary Outcome Measures:
  • Ongoing Pregnancy Rate [ Time Frame: 18 weeks after intrauterine insemination ] [ Designated as safety issue: No ]
    Pregnancies continued beyond 20 weeks gestation


Enrollment: 214
Study Start Date: September 2008
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Clomiphene citrate 100mg/day from cycle day 3 to 7

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 .

  Eligibility

Ages Eligible for Study:   18 Years to 37 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232075

Locations
Egypt
Ahmed Elgazzar hospital
Cairo, Egypt
Cairo university hospital
Cairo, Egypt
Sponsors and Collaborators
Cairo University
Ahmed Elgazzar Hospital
Investigators
Study Chair: Usama M Fouda, M.D, PhD Cairo University
Study Director: Ahmed M Sayed, M.D, PhD Cairo University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Usama Fouda,M.D, PhD, Cairo university
ClinicalTrials.gov Identifier: NCT01232075     History of Changes
Other Study ID Numbers: clomid/extended letr/unexp.inf
Study First Received: November 1, 2010
Last Updated: July 11, 2011
Health Authority: Egypt: Institutional Review Board

Keywords provided by Cairo University:
Letrozole ,Clomiphene citrate , IUI,unexplained infertility

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Chorionic Gonadotropin
Clomiphene
Enclomiphene
Zuclomiphene
Citric Acid
Letrozole
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Anticoagulants
Hematologic Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Fertility Agents, Female
Fertility Agents
Selective Estrogen Receptor Modulators
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 15, 2014