Effect of Vaginal Sildenafil Citrate on Endometrial Preparation and Outcome in Frozen Thawed Embryo Transfer Cycles

Study Overview
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Brief Summary
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A total of 80 Patients who meet these conditions will enter the study and be divided into two groups based on randomized tables. To prepare the endometrium, Group A : 40 women are given oral estradiol valerate tablets 2mg 6-8 hourly from the day 2-14 of the cycle to prepare the endometrium Group B : 40 women are give sildenafil citrate 25mg vaginally every 6 hours (a half of 50 mg tablet is crushed and dissolved in 2cc of distilled water and injected in to vagina) starting from day 2-14 of the cycle, in addition to oral 2mg of estradiol valerat 6-8 hourly from the day 2-14 of the menstrual cycle . Estrogen and progesterone (prontogest 400mg pessaries ) are given 3 days prior to embryo transfer. Sildenafil is discontinued 48-72 hours prior to the embryo transfe due sildenafil may have some detrimental effects on endometrium in the implantation window

Detailed Description
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A total of 80 Patients who meet these conditions will enter the study and be divided into two groups based on randomized tables. To prepare the endometrium, Group A : 40 women are given oral estradiol valerate tablets 2mg 6-8 hourly from the day 2-14 of the cycle to prepare the endometrium Group B : 40 women are give sildenafil citrate 25mg vaginally every 6 hours (a half of 50 mg tablet is crushed and dissolved in 2cc of distilled water and injected in to vagina) starting from day 2-14 of the cycle, in addition to oral 2mg of estradiol valerat 6-8 hourly from the day 2-14 of the menstrual cycle . Estrogen and progesterone (prontogest 400mg pessaries ) are given 3 days prior to embryo transfer. Sildenafil is discontinued 48-72 hours prior to the embryo transfe due sildenafil may have some detrimental effects on endometrium in the implantation window. For assessing endometrial vascularity (on day 14 of cycle), two dimension power Doppler characteristics as normal quality of color, color gain-3.4, pulse repetition frequency of 600Hz and wall motion filter of 50Hz are applied in all examinations. By following Applebaum's zones of vascularity for categorizing endometrial vasculaity: Zone 1 vascularity-When blood vessls reach the hypoechoic endometrio-myometria junction, Zone 2 vascularity when the vessels reach the outer hyperechoic line of en-dometrium, Zone 3 vascularity when it reach the intervening hypoechoic area, Zone 4 vascularity when the vessels are seen reaching the central echogenic line . After 5 days when the endometrial pattern is triple line pattern (trilaminar) and endometrial thickness is more than 8mm,embryos will be transferred. All patients have a luteal phase support by giving a daily doses of estradiol valerat 2mg oral daily and 100mg progesterone (prontogest 100mg ampoule ) as an intramuscular which will be continued two weeks after the em-bryos transfer. In case BHCG is tested and proved to be positive, estradiol valerat and progesterone are continueed until the 11th week of pregnancy. Then, four weeks after the embryo transfer, the number of gestational sacs are determined by vaginal ultrasound.

Official Title
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Effect of Vaginal Sildenafil Citrate on Endometrial Preparation and Outcome in Frozen Thawed Embryo Transfer Cycles

Conditions
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Infertility

Intervention / Treatment
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* Drug: sildenafil citrate
* Drug: Estradiol Valerate 2 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women undergoing their first frozen embryo transfer cycle. have at least two high quality frozen embryos Exclusion Criteria: 1. a history of endocrine diseases. 2. a history of hysteroscopic surgeries. 3. cardiovascular, renal and liver diseases. 4. hypotension (blood pressure <90/50 mmHg). 5. a history of stroke or myocardial infarction.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil group<br>40 women are give sildenafil citrate 25mg vaginally every 6 hours (a half of 50 mg tablet is crushed and dissolved in 2cc of distilled water and injected in to vagina) starting from day 2-14 of the cycle, in addition to oral 2mg of estradiol valerat 6-8 hourly from the day 2-14 of the menstrual cycle | Drug: sildenafil citrate<br>* 25mg vaginally every 6 hours (a half of 50 mg tablet is crushed and dissolved in 2cc of distilled water and injected in to vagina) starting from day 2-14 of the cycle<br>Drug: Estradiol Valerate 2 MG<br>* 2mg 6-8 hourly from the day 2-14 of the cycle to prepare the endometrium<br>|
| Active Comparator: estradiol group<br>40 women are given oral estradiol valerate tablets 2mg 6-8 hourly from the day 2-14 of the cycle to prepare the endometrium in addition to placebo in the same way as sildenafil | Drug: Estradiol Valerate 2 MG<br>* 2mg 6-8 hourly from the day 2-14 of the cycle to prepare the endometrium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endometrial thickness | ultrasound measurement of the endometrial thickness at the fundus | At the day of embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial vascularity | two dimension power Doppler characteristics as normal quality of color, color gain-3.4, pulse repetition frequency of 600Hz and wall motion filter of 50Hz are applied in all examinations. By following Applebaum's zones of vascularity for categorizing endometrial vasculaity: Zone 1 vascularity-When blood vessls reach the hypoechoic endometrio-myometria junction, Zone 2 vascularity when the vessels reach the outer hyperechoic line of en-dometrium, Zone 3 vascularity when it reach the intervening hypoechoic area, Zone 4 vascularity when the vessels are seen reaching the central echogenic line | At the day of embryo transfer | 
| clinical pregnancy rate | detection of intrauterine gestational sac by transvaginal ultrasound | 4 weeks after embryo transfer |