Effect of Ubiquinol Supplementation on Ovulation Induction in Clomiphene Citrate Resistance
Condition: Polycystic Ovarian Syndrome
MeSH terms: Polycystic Ovary Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Objective: To evaluate potential benefits of adding the active form of Coenzyme Q10
      (Ubiquinol) to Clomiphene Citrate compared with Human Menopausal Gonadotropins (hMG) in
      Clomiphene Citrate resistant PCOS patients.

      Methods: 148 PCOS Patients with Clomiphene Citrate resistance were randomized into two groups
      (A and B). In group A, controlled ovarian stimulation was done by Clomiphene Citrate 150 mg
      daily (from 2nd till 6th day of cycle) together with Ubiquinol starting from 2nd day till day
      of hCG triggering in a dose of 100 mg orally once daily. In group B, hMG was given from 2nd
      day of the cycle in a dose ranging from 75 to 225 IU. Serial transvaginal ultrasonography was
      done starting on cycle day 8 and continued till size of leading follicle reaches 18 mm or
      more then ovulation triggering was done. Thereafter, patients were advised for a timed
      intercourse (TI) after 36 hours. A blood sample was withdrawn seven days after hCG
      triggering, for measurement of serum progesterone. If the Patient presented with a missed
      period for one week, a serum sample was sent for β-hCG.
    

Detailed description: 
      Patients were divided randomly into two groups (A and B), who underwent controlled ovarian
      stimulation and timed intercourse, using random table computer software (Open Epi version
      3.21).

      Basal transvaginal ultrasonography (TVS) was done on day 2 of the cycle before commencing
      ovarian stimulation. For patients presenting with amenorrhea or oligomenorrhea,
      dydrogesterone 10 mg (Duphaston®; Abbott Biologicals B.V.) was prescribed (3 times daily for
      10 days) to achieve withdrawal bleeding before starting induction of ovulation.

      In group A, controlled ovarian stimulation (COS) was done by Clomiphene Citrate (Fertab® 50
      mg tablets, Zynova. SITCO Pharma.) as 150 mg (3 tablets) daily for 5 days (from 2nd day till
      6th day of the cycle) together with Ubiquinol (active form of Coenzyme Q10) starting from 2nd
      day till the day of human Chorionic Gonadotropin (hCG) triggering in a dose of 100 mg
      capsules orally once daily, immediately after meal (Nutraquinol®; Jamjoom Pharma
      Nutraceuticals). In group B, Human Menopausal Gonadotropins (hMG) (Merional® 75 I.U. vials,
      IBSA.) IM was given from 2nd day of the cycle in a dose ranging from 75 to 225 IU according
      to the patient's response. Patients were instructed not to take any non-study drugs during
      the whole study period. All patients did not receive any drug for induction of ovulation 3
      months prior to participation in the study.

      Serial transvaginal ultrasonography was done for assessment of follicular growth (number and
      diameter of follicles) and endometrial thickness (measured on sagittal view of the uterus by
      including the whole endometrium at the point of its maximum thickness), starting on cycle day
      8, using vaginal 4.5 MHz endocavity transducer (Esaote Mylab 50 Xvision Ultrasound, Italy),
      and was continued with an interval of 1-3 days till the size of the leading follicle reaches
      18 mm or more in mean follicular diameter. Then ovulation triggering was done by an
      intramuscular single dose of human Chorionic Gonadotropin (Epifasi® 5000 IU vials, EIPICO,
      Egypt.) 2 vials (10,000 IU). Thereafter, patients were advised for a timed intercourse (TI)
      36 hours after ovulation triggering.

      All measurements were obtained by a blinded single operator. All data were digitally stored
      and were not analyzed till the end of the study.

      Thereafter, patients were asked to come for follow up, 7 days after hCG triggering, where a
      blood sample (2 mL) was withdrawn for measurement of serum progesterone (ng/ml). Collected
      samples were centrifuged and then stored at 2-8 °C until enzyme immunoassay was done. If the
      Patient presented with a missed period for a week, a serum sample was sent for β-hCG using
      immunoassay.

      Patients with positive serum pregnancy test, defined as β-hCG concentration >10 mU/ml, were
      examined by abdominal ultrasonography 6 weeks after the first day of their last menstrual
      period with 3.5 MHz sector transducer (Esaote Mylab 50 Xvision Ultrasound, Italy) to detect
      an intrauterine gestational sac (Clinical pregnancy). Patients who failed to get pregnant
      were requested for follow up for 2 more consecutive cycles with the same protocol.

      The primary outcomes measured were; number of cases achieving follicular growth to the size
      of mature follicle ≥ 18 mm (1-3 follicles) during the three cycles of stimulation, number of
      stimulated cycles (till pregnancy occurs or completing the 3 cycles of the study, whichever
      is earlier), the endometrial thickness on the day of triggering, and the luteal function as
      assessed by mid-luteal serum progesterone measurements.

      The secondary outcomes were; number of cases with positive serum pregnancy test and the
      clinical pregnancy rate among the two groups during the three cycles of treatment.
    

Intervention name(s): Controlled ovarian stimulation by Combined Clomiphene Citrate and Ubiquinol Versus hMG
Intervention type(s): Drug
Intervention description(s): In group A, controlled ovarian stimulation (COS) was done by Clomiphene Citrate (Fertab® 50 mg tablets, Zynova. SITCO Pharma.) as 150 mg (3 tablets) daily for 5 days (from 2nd day till 6th day of the cycle) together with Ubiquinol (active form of Coenzyme Q10) starting from 2nd day till the day of human Chorionic Gonadotropin (hCG) triggering in a dose of 100 mg capsules orally once daily, immediately after meal (Nutraquinol®; Jamjoom Pharma Nutraceuticals). In group B, Human Menopausal Gonadotropins (hMG) (Merional® 75 I.U. vials, IBSA.) IM was given from 2nd day of the cycle in a dose ranging from 75 to 225 IU according to the patient's response. Patients were instructed not to take any non-study drugs during the whole study period.
Other intervention name(s): Fertab® 50 mg tablets, Zynova. SITCO Pharma.; Nutraquinol®; Jamjoom Pharma Nutraceuticals; Merional® 75 I.U. vials, IBSA
Intervention MeSH terms: Clomiphene; Enclomiphene; Zuclomiphene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment