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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sildenafil & Clomiphene Group | Active Comparator | 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. |
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| IUI & Clomiphene Group | Active Comparator | 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. |
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| Clomiphene only Group | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clomiphene Citrate. | Drug | Clomiphene Citrate (Clomid®) 100 mg for 5 days starting from the second day of the menstrual cycle (Groups A, B, and C). |
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| Measure | Description | Time Frame |
|---|---|---|
| Pregnancy outcome | Ultrasound confirmation of intrauterine fetal heartbeat. | 7 weeks after positive pregnancy test. |
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Inclusion Criteria:
Exclusion Criteria:
Females with unexplained infertility.
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| Name | Affiliation | Role |
|---|---|---|
| Remah M Kamel, PhD | Batterjee Medical College | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Batterjee Medical College | Jeddah | Mecca Region | 21442 | Saudi Arabia |
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| ID | Term |
|---|---|
| D002996 | Clomiphene |
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
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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).
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Double (Clinical investigator; the Radiologist, and Biostatistician; data analyst).
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| Sildenafil Citrate | Drug | 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). |
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| Intrauterine Insemination | Procedure | IUI (Group-B). |
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| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |