Extended Letrozole Regimen Versus Clomiphene Citrate for Superovulation in Patients With Unexplained Infertility Undergoing Intrauterine Insemination
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 2

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 .
    

Intervention name(s): Extended letrozole regimen; Clomiphene citrate regimen
Intervention type(s): Drug; Drug
Intervention description(s): 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 .; 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 intervention name(s): letrozole 2.5mg/day from cycle day 1 to 9; Clomiphene citrate 100mg/day from cycle day 3 to 7
Intervention MeSH terms: Letrozole; Citric Acid; Sodium Citrate; Clomiphene; Enclomiphene; Zuclomiphene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Letrozole ,Clomiphene citrate , IUI,unexplained infertility