Extended Letrozole Regimen Versus Clomiphene Citrate for Superovulation in Patients With Unexplained Infertility Undergoing Intrauterine Insemination
Information source: Cairo University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Infertility
Intervention: Extended letrozole regimen (Drug); Clomiphene citrate regimen (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Cairo University Official(s) and/or principal investigator(s): Usama M Fouda, M.D, PhD, Study Chair, Affiliation: Cairo University Ahmed M Sayed, M.D, PhD, Study Director, Affiliation: Cairo University
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 .
Clinical Details
Official title: Extended Letrozole Regimen Versus Clomiphene Citrate for Superovulation in Patients With Unexplained Infertility Undergoing Intrauterine Insemination
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Clinical pregnancy rate
Secondary outcome: Ongoing Pregnancy Rate
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
Minimum age: 18 Years.
Maximum age: 37 Years.
Gender(s): Female.
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
Locations and Contacts
Ahmed Elgazzar hospital, Cairo, Egypt
Cairo university hospital, Cairo, Egypt
Additional Information
Related publications: Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertil Steril. 2009 Jul;92(1):236-9. doi: 10.1016/j.fertnstert.2008.04.065. Epub 2008 Aug 15. Badawy A, Elnashar A, Totongy M. Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial. Fertil Steril. 2009 Oct;92(4):1355-9. doi: 10.1016/j.fertnstert.2008.06.013. Epub 2008 Aug 9.
Starting date: September 2008
Last updated: July 11, 2011
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