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Recurrent unexplained spontaneous miscarriage (RSM) is defined as three consecutive pregnancy loss prior to 20 weeks from the last menstrual period. 1% to 2% of women experience RSM. Treatment of URSM is a challenging issue. The currently available lines of treatment according to simplicity of use, reliability and degree of invasiveness include corticosteroids, sildenafil citrate, aspirin, heparin and immunoglobulins (besides good antenatal care), but up to now there are no prospective randomized studies, powerful enough, to determine a significant difference between these therapeutic protocols, with any of the above mentioned pharmacological agents.
Sildenafil Citrate (Viagra®), a vasodilator, is also described as an anti-inflammatory agent. While improving uterine blood flow in the proliferative phase, NO may have detrimental effects at the level of the endometrium during the implantation window. The NO- mediated release of cytokines such as tumour necrosis factor- from activated natural killer cells has been implicated as a cause of implantation failure.
Based on these observations, this study attempts was made to study uterine arteries and sub-endometrial blood flow during the luteal phase in normal fertile women and in patients with Unexplained recurrent miscarriage
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sildenafil group | Active Comparator | Includes 45 women who received Sildenafil citrate (Respatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period) and folic acid (Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally). |
|
| Control group | Active Comparator | Includes 45 women who received placebo oral tablets (apparently identical to Respatio(R) 25mg tablets, four times daily for 24 days preconceptionally starting first day of previous period) and folic acid (Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil Citrate | Drug | Respatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period |
|
| Measure | Description | Time Frame |
|---|---|---|
| Miscarriage rate | number of spontaneous/missed miscarriages among the participants in both groups | 24 gestational weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Uterine artery resistance index | Uterine artery resistance index assessed by uterine artery Doppler study in ongoing pregnancies of both groups | At 24 gestational weeks |
| Uterine artery pulsatility index |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mohamed Yakout, MBBCh | M Yakout | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ain SHams Maternity Hospital | Cairo | Abbaseya | 002 | Egypt |
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| ID | Term |
|---|---|
| D000026 | Abortion, Habitual |
| ID | Term |
|---|---|
| D000022 | Abortion, Spontaneous |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| D005492 | Folic Acid |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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Patients will be randomized into two groups: Group (A) folic acid and sildenafil citrate and Group (B) folic acid and placebo.
Folic acid (0.5 mg) will be started 3 months before conception in the two groups. Sildenafil citrate (dose: 25 mg; oral tablets, 4 times/day) or placebo will be started preconception for 24 days
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Patients are randomized to receive either folic acid and sildenafil citrate or folic acid and placebo. Placebo tablets were same size and appearance of the sildenafil citrate tablets.
| Folic Acid | Drug | Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally |
|
| Placebo Oral Tablet | Drug | Placebo tablet apparently identical to Respatio(R) 25mg tablets, taken four times daily for 24 days preconceptionally starting first day of previous period |
|
Uterine artery pulsatility index assessed by uterine artery Doppler study in ongoing pregnancies of both groups
| At 24 gestational weeks |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011622 | Pterins |
| D011621 | Pteridines |