Clinical trial NCT03301233: Effect Sildenafil and Estradiiol Valerate on Endometrial Thickness in Infertile Women
Official title: The Effect of Estradiol Valerate With and Without Oral Sildenafil on Endometrial Thickness and Pregnancy Rates in Infertile Women: A R.C.T
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endometrial Thickness
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2017-10-04
Enrollment: 90
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Patients having ovulatory infertility.
2. Age: 20-35 years old.
3. BMI less than 30 kg/m2

Exclusion Criteria:

1. Women who have any congenital uterine anomaly (e.g., unicornuate uterus or infantile uterus) or acquired deformities of the uterine cavity that interfere with embryo implantation (as Asherman Syndrome).
2. Women who have any tubal factor that relates to infertility (e.g., tubal adhesion or previous ectopic pregnancy).
3. Women who have contraindication for estrogen treatment (e.g., history of stroke, DVT and Benign liver disease).
4. Women who have male factor for infertility (e.g., azoospermia, teratospermia).

Primary outcomes:
measure: endometrial line thickness
timeFrame: 9 days
Secondary outcomes:
measure: positive pregnancy test
timeFrame: 14 days after triggering of ovulation
measure: sub endometrial blood flow
timeFrame: 9 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University
Study officials:
affiliation: Ain Shams University
name: Hayam F Mohammad, MD
role: PRINCIPAL_INVESTIGATOR
References: