Effect of Sildenafil Citrate on Mid Luteal Phase Uterine Artery Blood Flow in Patients With Recurrent Pregnancy Loss
Condition: Recurrent Pregnancy Loss
MeSH terms: Abortion, Spontaneous; Fetal Death; Abortion, Habitual; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      Patients with recurrent pregnancy loss are known to have decreased uterine artery blood flow.
      Nitric oxide plays a major role in increasing uterine blood flow during the luteal phase.
      This study is done to evaluate the effects of sildenafil on blood flow indices in the
      patients with recurrent pregnancy loss due to impaired uterine artery blood flow.
    

Detailed description: 
      Study Setting: The study will be conducted in recurrent pregnancy loss outpatient clinic at
      Ain shams university maternity hospital.

      Study Population: Patients with unexplained recurrent miscarriage attending Ain shams
      university maternity hospital's outpatient clinic. This study will be conducted on 80 women
      distributed into 2 groups each is 40 women in fertile age with history of two or more
      recurrent spontaneous abortions and decreased uterine artery blood flow(PI>2.02(Mansour et
      al., 2018). First group will be placebo controlled and the second group will be given
      sildenafil citrate.

      Women will be asked to attend during the 21-23 day of the cycle and will be subjected to:
      History taking and Full clinical examination.

      Clinical examination will be done including general, abdominal and pelvic examination.

      General examination: including general appearance, weight, height and vital signs Abdominal
      examination: to assure freedom of any organic clinically detectable pathologic lesions.

      Pelvic examination: included inspection of the external genitalia, speculum examination of
      the vagina to rule out infection, and bimanual assessment of uterine size and position as
      well as exclusion of adnexal masses.

      Laboratory investigations:

      Routine investigations including: CBC, fasting and postprandial blood sugar, urine analysis,
      kidney function and liver function will be done.

      The endocrine evaluation consisted in measuring thyroid-stimulating hormone, free thyroxin,
      and progesterone levels on day 21 of the menstrual cycle.

      Sonography:

      Sonography will be performed using Samsung H60 with convex probe (multi-frequency AD 2~ 8
      MHz) to perform trans-vaginal examination. Examination will be performed in the second phase
      of the menstrual cycle, at mid-luteal day.

      Pulsed wave Doppler will be used to obtain clear, consistent, flow velocity wave forms of
      both uterine arteries. Pulsatility index (PI) will be measured bilaterally. The PI reported
      will be the arithmetic mean for the last three cardiac cycles.

      (Goswamy and Steptoe, 1988) classification will be used to determine the wave types.
      According to this classification, the FVW of the circumflex artery can be of 3 types : Type A
      when the diastolic component is present but not continuous with the systole, and ends before
      the next cardiac cycle.

      Type B when a diastole is present and continues with the systole, but ends before the next
      cardiac cycle.

      Type C when a diastole is present and continues with the systole and into the next cardiac
      cycle.

      The majority of research has centered on an elevation in the RI or PI to detect the presence
      of increased uterine artery blood flow resistance in non- pregnant states. Criteria for an
      abnormal uterine artery Pulsatility index (PI) cutoff (PI> 2.02) and abnormal sub-endometrial
      blood flow Resistant Index (RI) (RI>0.6) (Mansour et al., 2018).

      Steps and methods:

      The participants will be two groups of 80 patients with history of recurrent pregnancy loss,
      each is 40.

      All patients will be scanned transvaginally with transvaginal Doppler sonography 6 to 8 days
      after ovulation to measure the pulsatility index (PI), resistance index (RI) and systolic to
      diastolic ratio (S/D) of the right and left main uterine arteries and sub-endometrial blood
      flow resistance index (RI). Sildenafil citrate at a dose of 25mg or placebo will be
      administered orally in patients with recurrent pregnancy loss and the blood flow indices will
      be measured after 3 hours. The student test will be used for analysis of the results, P< 0.05
      will be considered significant.

      With 95% confidence interval. P values ≥5% considered to be significant.
    

Intervention name(s): Sildenafil 25Mg Tablet; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Sildenafil citrate at a dose of 25mg will be administered orally in patients with recurrent pregnancy loss; placebo will be administered orally in patients with recurrent pregnancy loss
Intervention MeSH terms: Sildenafil Citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment