Mild Stimulation Protocol Using Clomiphene Citrate for Women With PCOS Undergoing in Vitro Fertilization

NCT04157725 | Unknown Phase 4 DMC

• 1 other identifier: AmericanUBMC-MS
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

Infertility is of increasing significance affecting almost 48.5 million couples around the world. Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. Ultrasound morphological features of PCOS include the presence of 16 or more follicles measuring 2-9 mm in diameter, and/or an overall large ovarian volume of \>10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation. Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome, IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable. Recently, patient-friendly stimulation protocols for assisted reproductive technology were introduced aiming at minimizing overall treatment costs and health hazards to the patient. Mild stimulation protocols are considered relatively novel protocols. They consist of combining oral stimulation agents (clomiphene citrate or letrozole) with low-dose gonadotropins as effective alternatives to conventional gonadotropin-only stimulation protocols. Mild stimulation protocol has been associated with better tolerance, ease of use, and comparable livebirth outcomes. The investigators aim to test the hypothesis that mild stimulation protocols could produce a similar proportion of term livebirths to conventional treatment, while reducing treatment costs and health hazards. This is a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.

Conditions

PCO - Polycystic Ovaries; Infertility

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Defined as number of viable fetuses above 24 weeks of gestation per number of embryos transferred

  more than 24 weeks of gestation

Secondary Outcomes (11)

• Total number of gonadotropins

  up to 2 weeks

• Duration of stimulation

  up to 2 weeks

• total number of developing follicles

  up to 2 weeks

• Rate of GnRHa trigger of final follicle maturation, endometrial thickness and pattern.

  up to 2 weeks

• Fertilization rate

  up to 1 week

Study Arms (2)

Group A (mild stimulation protocol)

EXPERIMENTAL

Drug: mild stimulation protocol: oral Clomiphene Citrate

Group B (conventional stimulation protocol)

ACTIVE COMPARATOR

Drug: Conventional Stimulation Protocol: will receive FSH/HMG

Interventions

mild stimulation protocol: oral Clomiphene Citrate DRUG

Group A (mild stimulation protocol) will receive oral Clomiphene Citrate (Clomid®) 150 mg/day for 5 days (starting on the 2nd of menses), followed by FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting from the 6th day of the menstrual cycle. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above.

Group A (mild stimulation protocol)

Conventional Stimulation Protocol: will receive FSH/HMG DRUG

Group B (conventional stimulation protocol) will receive FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting on the 2nd day of menses. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above.

Group B (conventional stimulation protocol)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: For women with PCOS who are undergoing IVF
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female patients between 18-40 years of age
• Antral follicle count exceeding 16 and/or AMH exceeding 3.5 ng/dl
• PCOS features as per Rotterdam criteria: 2 of 3 criteria: a. Ultrasound morphology; b. Oligo/amenorrhea; c. Hyperandrogenism (clinical or chemical).

You may not qualify if:

• Recurrent implantation failure
• Recurrent pregnancy loss
• Congenital uterine anomalies
• Untreated maternal medical conditions (Diabetes, thyroid disease…)

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

American University of Beirut Medical Center

Beirut, Lebanon

Location

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Johnny T Awwad, M.D

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics and Gynecology

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: November 8, 2019
• Study Start: June 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: July 1, 2025
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)