Clomiphene Citrate, Estradiol and Sildenafil for Induction of Ovulation in Unexplained Infertility
Condition: Female Infertility
MeSH terms: Infertility; Infertility, Female
Study type: Interventional
Phase: Phase 1

Summary: 
      Diagnosis of unexplained infertility is made after the recommended testing fails to reveal
      any abnormality. The treatment for unexplained infertility is empiric because it does not
      address a specific defect or functional impairment. The principal treatments for unexplained
      infertility include expectant observation with timed intercourse and lifestyle changes,
      clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation
      (COH) with IUI, and IVF).
    

Detailed description: 
      Clomiphene citrate has been widely used alone, and in combination with intrauterine
      insemination (IUI), for treatment of unexplained subfertility, The mechanism of action is
      based on its mixed estrogenic and antiestrogenic properties. Clomiphene is frequently used to
      treat unexplained female infertility by inducing multifollicular response and correcting
      potential subtle ovulatory dysfunction .,)The American Society for Reproductive
      Medicine,2003).

      The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase,
      a periimplantation stage., )The American College of Obstetricians and Gynecologists,1995).

      Although ovulation is found in 80% of women with a cumulative effect in 6-8 months, the
      pregnancy rate can still be very low in these women . The possible causes are the
      anti-estrogenic effects of CC at the endometrium and cervical mucus level . The endometrial
      effect is without doubt one of the most important handicaps in infertility treatment. The
      pregnancy rate can be very low, especially if the endometrial thickness (ET) is <6-8 mm ., )J
      Turk Ger Gynecol Assoc. ,2012).

      Ethinyl E2 reverse the deleterious effect of CC on endometrial development during the
      follicular phase. Endometrial thickness was dependent on peak E2 concentrations in
      serum.,(Richard P. Dickey, et.al.,2003).

      Sildenafil citrate could lead to an improvement in uterine blood flow and, in conjunction
      with estrogen, led to the estrogen-induced proliferation of the endometrial lining .

      Sildenafil citrate enhances uterine blood flow and increases endometrial thickening . The
      achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and
      develop a sustaining blood supply, which requires the following genes to produce the
      necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth,
      and to induce angiogenesis (Razieh Dehghani Firouzabadi,et.al.,2013).
    

Intervention name(s): Clomid, Respatio and Ethinyl estradiol
Intervention type(s): Drug
Intervention description(s): Drugs were received during the menstrual cycle.
Intervention MeSH terms: Ethinyl Estradiol; Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Women with unexplained infertility (n=150) were divided into 3 equal groups. Group 1 received estradiol and clomiphine citrate (cc), group 2 received sildenafil and cc and group 3 cc and placebo.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment