Effect Sildenafil and Estradiiol Valerate on Endometrial Thickness in Infertile Women
Condition: Endometrial Thickness
MeSH terms: Infertility
Study type: Interventional

Summary: 
      The endometrium is a dynamic tissue that responds to changing hormonal signals throughout the
      cycle. The changes in the endometrial composition are expressed in alteration in gene
      expression, micro architectural morphological changes as well as in protein and hormone
      secretion. These factors combine together to construct the "window of implantation" a short
      period of time during the luteal phase in which the endometrium is receptive.

      Thin endometrium is associated with a low pregnancy rate. Endometrial thickness 7 mm in the
      pre-ovulatory phase is widely accepted to be cut-off of thin endometrium.

      for that the aim of this study is to compare the effect of sildenafil-estrogen combination to
      estrogen alone on endometrium thickness in infertile women. Half of the patients will receive
      estrogen ( estradiol valerate ) and the other half will receive combination of
      sildenafil-estrogen .
    

Detailed description: 
      Being a hormone dependent tissue, the endometrium proliferates in response to estrogen, which
      further induces the production of progesterone receptors. As a result, infertile patients who
      demonstrated thin endometrium, were offered estradiol (E2) remedies, in an attempt to improve
      endometrial proliferation. Most of the studies regarding E2 treatment in patients with thin
      endometrium dealt with frozen-thawed embryo transfer cycles. Moreover, while there are
      several routes and duration of administration of E2, including per Os, transdermal,
      Intramuscular and vaginal, no compelling advantage for one protocol for endometrial
      preparation over another, with regard to pregnancy rates, has been established.

      Sildenafil acts as a type 5-specific phosphodiesterase inhibitor hence augments the
      vasodilatory effects of nitric oxide by preventing the degradation of cGMP. Nitric oxide (NO)
      relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have
      been identified in the uterus. A decade ago, Sher and Fisch studied the effect of vaginal
      sildenafil on the endometrial thickness of infertile patients with poor endometrial
      development, who underwent IVF treatment. They have demonstrated improved uterine artery
      blood flow and endometrial growth, with higher implantation and ongoing pregnancy rates
      following vaginal sildenafil administration.
    

Intervention name(s): estradiol valerate and sildenafil
Intervention type(s): Drug
Intervention description(s): (45 women will receive clomiphene citrate (clomid 50mg ®, Sanofi aventis) 2 tab. single dose orally from the 2nd day of the cycle for 5 days with oral estradiol valerate (Cyclo-Progynova ® 2mg, white tablets, BAYER Schering Pharma), one tablet every 12 hour from 2nd day of the cycle + sildenafil (silden® 25, E.I.P.I.CO.) every 8 hour from 2nd day of the cycle till the day of trigger of ovulation).
Other intervention name(s): cycloprogenova and silden
Intervention MeSH terms: Sildenafil Citrate; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic