Clinical trial NCT03481582: Effect of Nitric Oxide Donors on Uterine and Subendometrial Blood Flow in Patients With Unexplained Infertility
Official title: Effect of Nitric Oxide Donors on Uterine and Subendometrial Blood Flow in Patients With Unexplained Infertility
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Infertility, Female
Keywords: Nitroglycerin Trans-dermal Patch
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 60
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 90 female patients will be divided into 3 equal groups:

* Group I: 30 female patients with unexplained infertility.
* Group II: 30 female patients with unexplained infertility will receive nitroglycerin trans-dermal patch.
Primary purpose: TREATMENT

Brief summary: The purpose of the study to evaluate effect of nitroglycerin trans-dermal patches on uterine and sub-endometrial blood flow in women with unexplained infertility.

Detailed description: 90 female patients will be divided into 2 equal groups:

* Group I: 30 female patients with unexplained infertility.
* Group II: 30 female patients with unexplained infertility will receive nitroglycerin trans-dermal patch.

All subjects will be subjected to the following:

* Proper history taking on past medical history, menstrual history and infertility workup.
* Proper examination (general, abdominal and local examinations)
* Investigations to diagnose unexplained infertility ( male partner's semen analysis as well as documented ovulation and a patent uterine cavity and Fallopian tubes in the female partner).
* Group II (30 patients with unexplained infertility)will receive: (nitrodermal®) 5 mg (patch)as a source of Nitric oxide from 2nd day of cycle till maturation of the follicles ≥ 18 mm just for one cycle
* All women included in each group will be subjected to trans-vaginal ultrasound for folliculometry till maturation of the follicle ≥18mm.
* Once the follicle reached ≥18 mm 3D power Doppler will be used to assess the uterine and sub-endometrial blood flow.
* All women in each group will be subjected to urinary luteinizing hormone (LH) assay. The urinary LH assay will be started on cycle day 11, and repeated daily till detection of the LH surge.
* Six days after detection of the LH surge, 3D power Doppler will be repeated to assess the uterine and sub-endometrial blood flow.

Eligibility criteria: Inclusion Criteria:

1. Age between 20-35 years.6
2. Normal husband's semen analysis (WHO 2010 Criteria):

   * Count ≥15 million
   * Motility ≥ 32% progressive motility
   * Morphology ≥ 4% normal morphology
3. Documented ovulation ( basal body temperature , mid-luteal serum progesterone ≥3 ng / ml and ultrasound monitoring of ovulation).
4. Patent Fallopian tube and excluding uterine anomalies either by hystero-salpingogram (HSG) and/or laparoscopy.
5. Normal hormonal profile (serum progesterone, E2, F.S.H, LH and T.S.H In the 2ND Day of menstrual cycle)

Exclusion Criteria:

1. Male factor of infertility.
2. Patients with uterine pathology as fibroids.
3. Tubal factor of infertility diagnosed by hysterosalpingography (HSG) or laparoscopy.
4. Patients with any contraindications for NO such as chronic liver and renal disease, known cardiac disease and migraine.
5. Diagnosis of PCO based on Rotterdam criteria, two out of three of the following are required to make the diagnosis (Rotterdam, 2004):

   * Oligo- and/or anovulation.
   * Clinical and/or biochemical signs of hyperandrogenism.
   * Polycystic ovaries (by transvaginal ultrasound): the morphology of PCO has been defined as an ovary with 12 or more follicles measuring 2-9 mm in diameter and/or increased ovarian volume (\>10 cm3) (Balen et al, 2003).
6. Conditions that mimic PCOS; disorders that cause oligo/anovulation and/or hyperandrogenism, such as:

   * Thyroid disease.
   * Non classic congenital adrenal hyperplasia.
   * Hyperprolactinemia.
   * Androgen-secreting tumors.
7. Women who had any medical comorbidity (e.g. autoimmune disease or diabetes mellitus) and those who have been using medications to induce ovulation or medications known to affect the VEGF concentration (NSAIDs) were not included in the study.

Primary outcomes:
measure: Three dimensional power Doppler
timeFrame: from day 10 of menstrual cycle until the follicle reached ≥18 mm
Secondary outcomes:
measure: Pregnancy rate
timeFrame: 2 weeks after follicle reached ≥18 mm
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Department of obstetrics and gynaecology, faculty of medicine, Ain shams university
Study officials:
References: