Cost-effective Treatment of Unexplained Infertility

Study Overview
=================
Brief Summary
-----------------
The issue of unexplained infertility that Southam brought up in 1960 is still a problem today. Despite improvements in infertility assessment, many couples still don't know why they are infertile. Even with the use of the most advanced ovulation detectors, fallopian tube patency tests, and semen evaluations, competency cannot identify every potential flaw in the intricate processes leading to conception. Unexplained infertility will be a challenge for both biological and clinical researchers since it results from these gaps in our understanding of fertilization and from our incapacity to use all of the current evidence-based information.

Detailed Description
-----------------
For the treatment of unexplained infertility, Clomiphene Citrate (CC) is frequently used either alone or in conjunction with intrauterine insemination (IUI). Its combined oestrogenic and anti-oestrogenic characteristics serve as the basis for the mechanism of action. When clomiphene citrate is used, the uterine blood flow is reduced during the peri-implantation stage of early luteal phase. About 80% of women experience ovulation, which has a cumulative effect over 6 to 8 months, yet the pregnancy rate in these women can still be relatively low. The endometrial and cervical mucus-level anti-oestrogenic actions of CC are the potential culprits. Without a doubt, one of the biggest obstacles in treating infertility is the endometrial impact. If the endometrial thickness (ET) is less than 6 mm, the pregnancy rate may be extremely low. Sildenafil citrate promotes endometrial thickness and uterine blood flow. The capacity of the blastocyst to penetrate the endometrium and establish a lasting blood supply is crucial for successful implantation. To do this, the blastocyst needs genes in order to create the required proteins for breaking down the endometrial cellular matrix, control cell development, and trigger angiogenesis. It can be difficult to understand the evidence on the efficacy and security of therapy for unexplained infertility. Given the substantial proportion of unaided pregnancies with expectant management, it is problematic that most studies do not include a placebo or untreated control group.

Official Title
-----------------
Cost-effective Treatment of Unexplained Infertility: A Prospective Multicenter, Double-blinded, Randomised Controlled Study

Conditions
-----------------
Unexplained Infertility

Intervention / Treatment
-----------------
* Drug: Clomiphene Citrate.
* Drug: Sildenafil Citrate
* Procedure: Intrauterine Insemination


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Saudi women. Married women in a stable, continuous, unprotected heterosexual relationship (cohabitating with their husbands). Aged between 18 to 35 years old. Non-smoking. Non-alcohol drinking. With a body mass index < 30 Kg/M2, Who are looking healthy (all their infertility-workup investigations including male partners' seminal analysis were within normal range) Failed to conceive spontaneously within 2 years of marriage without evident cause (cases with primary infertility). Exclusion Criteria: All non-Saudi women, Saudi unmarried women (not yet engaged in sexual activity), Married women with age less than 18 or more than 35 years old, Patients with secondary infertility, Cigarette smokers. Alcohol drinking. BMI > 30 Kg/M2, Pregnant women. Breastfeeding women. With known pathological cause (either male or female factor), With hypersensitivity to any of medication planned to be used in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Couples with unexplained infertility (n=900) were divided into three equal groups. Group-A received Sildenafil Citrate (Viagra®) and Clomiphene Citrate (Clomid®). Group-B received Clomiphene Citrate (Clomid®) and subjected to intra-uterine insemination (IUI). Group-C received Clomiphen Citrate (Clomid®) alone (Control group).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sildenafil & Clomiphene Group<br>Sildenafil Acetate (Viagra®) 25 mg as a vaginal tablet 6 hourly for 10 days starting from the fifth day of the menstrual cycle + Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle. Follow-up by resistance index (RI), pulsatility index (PI), and maximum velocity (T-max) of sub-endometrial, uterine, and ovarian vessels measured by using TVS Colour Doppler ultrasound. | Drug: Clomiphene Citrate.<br>* Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle (Groups A, B, and C).<br>* Other names: Clomid®;Drug: Sildenafil Citrate<br>* Sildenafil Acetate (Viagra®) 25 mg as a vaginal tablet 6 hourly for 10 days starting from the fifth day of the menstrual cycle (Group-A).<br>* Other names: Viagra®;|
| Active Comparator: IUI & Clomiphene Group<br>Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle + Intrauterine insemination (IUI) 42 hours after human chorionic gonadotropin (Pregnyl®) 10,000 IU injection IM. Follow-up by resistance index (RI), pulsatility index (PI), and maximum velocity (T-max) of sub-endometrial, uterine, and ovarian vessels measured by using TVS Colour Doppler ultrasound. | Drug: Clomiphene Citrate.<br>* Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle (Groups A, B, and C).<br>* Other names: Clomid®;Procedure: Intrauterine Insemination<br>* IUI (Group-B).<br>* Other names: IUI;|
| Placebo Comparator: Clomiphene only Group<br>Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle. Follow-up by resistance index (RI), pulsatility index (PI), and maximum velocity (T-max) of sub-endometrial, uterine, and ovarian vessels measured by using TVS Colour Doppler ultrasound. | Drug: Clomiphene Citrate.<br>* Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle (Groups A, B, and C).<br>* Other names: Clomid®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy outcome | Ultrasound confirmation of intrauterine fetal heartbeat. | 7 weeks after positive pregnancy test. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clomiphene citrate, Sildenafil citrate, Intrauterine insemination, Unexplained Infertility