Effect of Ubiquinol Supplementation on Ovulation Induction in Clomiphene Citrate Resistance

Polycystic Ovarian Syndrome Clinical Trial

Official title: Effect of Ubiquinol Supplementation on Ovulation Induction in Clomiphene Citrate Resistance

Status Completed

Clinical Trial 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 A blood sample was withdrawn seven days after hCG triggering, for measurement of serum progesterone.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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome

• NCT number: NCT04870502
• Study type: Interventional
• Source: Saudi German Hospital - Madinah
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 1, 2019
• Completion date: July 31, 2020