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Sildenafil Citrate in Early Unexplained Recurrent Pregnancy Loss

Phase 1
Completed
Conditions
Miscarriage, Recurrent
Interventions
Registration Number
NCT03766594
Lead Sponsor
Ain Shams University
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
90
Inclusion Criteria
  • Age: 20-35 years.
  • BMI (20-30)
  • History of three or more successive unexplained recurrent miscarriage.
  • Normal uterine cavity by hystrography or hysteroscopy.
  • No luteal phase defects by progesterone > 10 ng.
  • Normal thyroid function (TSH, T3, T4)
  • Normal lupus anticoagulant measured by activated partial throbmoplastine time (32-43 seconds).
  • Normal anticardolipin (IgG < 20 gpl and IgM < 15 MPL measured by ELISA).
  • Normal anti thyroid antibodies.
  • Normal glucouse tolerance test.
  • Normal parental karyotyping.
Exclusion Criteria
  • Age<20 or>35 year
  • BMI<20 or>30
  • Systemic diseases that might affect pregnancy such as diabetes or thyroid disorders or hypertension.
  • History of consanguinity.
  • Family history of chromosomal abnormalities (e.g. trisomy 21, trisomy 13, Turner's disease ...etc.).
  • History of autoimmune diseases, eg: systemic lupus.
  • Congenital anomaly in uterine cavity as bicornate or septate uterus.
  • Luteal phase defect and corpus luteum insufficiency.
  • Uterine masses as fibroid or polyps.
  • Patient with patuoles os.
  • patient with antiphosphlipid syndrome.
  • Cigarette smoking and alcohol.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control groupPlacebo Oral TabletIncludes 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).
Sildenafil groupSildenafil CitrateIncludes 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 groupFolic AcidIncludes 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).
Sildenafil groupFolic AcidIncludes 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).
Primary Outcome Measures
NameTimeMethod
Miscarriage rate24 gestational weeks

number of spontaneous/missed miscarriages among the participants in both groups

Secondary Outcome Measures
NameTimeMethod
Uterine artery pulsatility indexAt 24 gestational weeks

Uterine artery pulsatility index assessed by uterine artery Doppler study in ongoing pregnancies of both groups

Uterine artery resistance indexAt 24 gestational weeks

Uterine artery resistance index assessed by uterine artery Doppler study in ongoing pregnancies of both groups

Trial Locations

Locations (1)

Ain SHams Maternity Hospital

🇪🇬

Cairo, Abbaseya, Egypt

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