Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility

NCT04071574 | Completed Phase 1

• 1 other identifier: LU-MC-001/18
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The study will describe the effectiveness of ovarian stimulation in correlation with female infertility causes in a Lebanese population: a comparative study using 5 protocols of ovulation induction (treatment with "A" gonadotropins alone, "B" short GnRH agonist, "C" multiple-dose GnRH antagonist, "D" long GnRH agonist and "E" combined protocol of GnRH antagonist and agonist) and the outcomes of ICSI. This comparative study will help clinicians to select the relevant protocol of ovarian stimulation related to the female infertility disorders.

Conditions

Female Infertility; Female Infertility Due to Ovulatory Disorder; Premature Ovarian Failure; Polycystic Ovary Syndrome; Female Infertility of Tubal Origin; Ectopic Pregnancy; Salpingitis; Female Infertility Due to Tubal Block; Female Infertility Due to Tubal Occlusion; Hydrosalpinx; Female Infertility - Cervical/Vaginal; Female Infertility Endocrine; Endometriosis; Fibroids; Congenital Uterine Anomaly; Infections Uterine; Female Infertility of Other Origin

Keywords

Infertility; Ovarian; Ovulation; IVF; ICSI; Gonadotropin

Outcome Measures

Primary Outcomes (1)

• Ovulation Induction

  Monitoring of Ovulation Stimulation by trans-vaginal ultrasound determining the growth, number and appearance of the ovarian follicles as well as the maturation of the endometrium (measurement of its thickness); Follicles are considered mature when their diameter is greater than 18-20mm and each of them provides 250-300pg/mL of E2. When these criteria are obtained, ovulation is triggered

  36 hours

Secondary Outcomes (4)

• fertilization rate

  12 months

• embryo quality

  12 months

• pregnancy rate

  12 months

• live birth rate

  12 months

Study Arms (5)

Protocol "A"

ACTIVE COMPARATOR

Protocol with gonadotropins alone without agonist or antagonist: Gonadotropin treatment begins after spontaneous menses. The gonadotropins (e.g. Menopur, 150-225IU) are injected daily from D2/3 of the cycle (Gonadotropin dose varies based on the follicular response). The moment to trigger ovulation by administration of HCG (e.g. Ovitrelle or Pregnyl, 10.000IU) is determined by monitoring ovulation (folliculogenesis) approximately 14 days after gonadotropins regimen and the presence of at least 3 follicles with 18 mm sizes and at least the levels of E2 reaches 250-300 pg/ml. 36 h after HCG triggering, the mature oocytes are retrieved.

Drug: Human Chorionic Gonadotropin (hCG); Drug: Gonadotropins

Protocol "B"

ACTIVE COMPARATOR

Short GnRH agonist protocol: For the short GnRH agonist protocol, the administration of gonadotropins begins at the same time as that of the agonist, which makes it possible to take advantage of the action of endogenous gonadotropins released by the flare-up effect of the agonist. A low dose of GnRH agonist (e.g., triptorelin (Decapeptyl 0.1mg/day)) is administered in parallel to gonadotropin (e.g. Menopur, 150-225 IU) daily starting on cycle-day 2 (Gonadotropin dose varies based on the follicular development). Continual administration of GnRH agonist and gonadotropin lasts until HCG triggering (e.g. Ovitrelle or Pregnyl, 10.000IU), \~14 days post GnRH agonist regimen when follicles size reached 16-18 mm and at least the levels of E2 reaches 250-300 pg/ml. 36 h after HCG triggering, the mature oocytes are retrieved.

Drug: Human Chorionic Gonadotropin (hCG); Drug: Gonadotropins; Drug: GNRH-A Triptorelin

Protocol "C"

ACTIVE COMPARATOR

Multiple-dose antagonist protocol: For the GnRH antagonist protocol, a low dose of GnRH antagonist (0.25 mg/day) is administered. The protocol starts with the administration of gonadotropin (e.g. Menopur, 150-225 IU) daily which is initiated after monitoring of patients' follicles sizes on cycle-day 2/3 (Gonadotropin dose varies based on the follicular response). Almost after the 6th days of gonadotropin injection or when follicular size reaches more than or equal to 14 mm, GnRH antagonist (e.g., cetrorelix (cetrotide) or ganirelix (orgulatron) 0.25mg) begins by subcutaneous administration every day till HCG triggering (e.g. Ovitrelle or Pregnyl, 10.000IU). 36 h after HCG triggering, the mature oocytes are retrieved.

Drug: Human Chorionic Gonadotropin (hCG); Drug: Gonadotropins; Drug: GnRH antagonist

Protocol "D"

ACTIVE COMPARATOR

Long GnRH agonist protocol: For the long GnRH agonist protocol, a low dose of GnRH agonist (e.g., triptorelin (Decapeptyl 0.1mg)) is administered on cycle-day 21 followed by gonadotropin (e.g. Menopur, 150-225 IU) daily starting on cycle-day 2 after menses (Gonadotropin dose varies based on the follicular development). Continual administration of GnRH agonist and gonadotropin lasts until HCG triggering (e.g. Ovitrelle or Pregnyl, 10.000IU), \~14 days post GnRH agonist regimen when follicles size reached 16-18 mm. 36 h after HCG triggering, the mature oocytes are retrieved.

Drug: Human Chorionic Gonadotropin (hCG); Drug: Gonadotropins; Drug: GNRH-A Triptorelin

Protocol "E"

ACTIVE COMPARATOR

Combined GnRH antagonist and agonist protocol: For the combined protocol, it starts with the administration of gonadotropin (e.g. Menopur, 150-225 IU) daily which is initiated after monitoring of patients' follicles sizes on cycle-day 2/3 (Gonadotropin dose varies based on the follicular response). Almost after the 6th days of gonadotropin injection or when follicular size reaches more than or equal to 14 mm, GnRH antagonist (e.g., cetrorelix (cetrotide) or ganirelix (orgulatron) 0.25mg) begins by subcutaneous administration every day till GnRH agonist injection (e.g., triptorelin (Decapeptyl 0.1mg/day)). 36 h after agonist injection, the mature oocytes are retrieved.

Drug: Gonadotropins; Drug: GNRH-A Triptorelin; Drug: GnRH antagonist

Interventions

Human Chorionic Gonadotropin (hCG) DRUG

Administration of hCG (10.000IU) for ovulation triggering

Also known as: OVITRELLE / PREGNYL

Protocol "A"; Protocol "B"; Protocol "C"; Protocol "D"

Gonadotropins DRUG

Administration of Menotropin (hMG / FSH and LH at a 1:1 ratio) (150-225IU/day)

Also known as: MENOPUR

Protocol "A"; Protocol "B"; Protocol "C"; Protocol "D"; Protocol "E"

GNRH-A Triptorelin DRUG

Administration of Triptorelin (0.1mg/day)

Also known as: DECAPEPTYL

Protocol "B"; Protocol "D"; Protocol "E"

GnRH antagonist DRUG

Administration of cetrorelix (cetrotide) or ganirelix (orgulatron) (0.25mg/day)

Also known as: CETROTIDE / ORGULATRON

Protocol "C"; Protocol "E"

Eligibility Criteria

• Age: 21 Years - 44 Years
• Gender Eligibility Details: The average age of the population must be around 30 years old. Note that no one of the 264 women in this study should have any chromosomal abnormalities or mutated genes that affect ovarian function.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• must not show any of the excluded criteria
• Patients affected by female infertility due to particularly Ovulatory Disorder, Premature Ovarian Failure, Polycystic Ovary Syndrome, Tubal Origin, Ectopic Pregnancy, Salpingitis, Tubal Block/Occlusion, Hydrosalpinx, Cervical/Vaginal, Endocrine, Endometriosis, Fibroids, Congenital Uterine Anomaly, Infections Uterine, and Female Infertility of Other Origin
• The selection of subjects' age must be group matched between protocols of treatment. Premature ovarian failure is defined as AMH (Anti Mullerian Hormone) ≤ 2 ng/mL.
• Willing to collaborate and to attend to the clinical follow-ups for the next three years
• Patients willing to sign informed consent
• Able and willing to comply with all study requirements
• Absence of genetic causes
• Medically suitable to undergo ovarian stimulation
• Normal serum chemistry and hematology screening tests
• Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) serology
• No history of malignancy
• Complete history \& physical examination

You may not qualify if:

• Subjects to be excluded from the study if the male (husband) had any male infertility problem(s)
• Patients with any genetic abnormalities
• Patients with histories of neurologic conditions including moderate or severe head injury, stroke, cerebral or bone damage or malignancies, brain abnormalities, learning disability, major medical or psychiatric illness, and metabolic/cardiovascular disease or evidence of cardiac/renal damage or malignancies, alcohol, loss of weight during the last 2 years, chemotherapy or immunosuppressive therapy.
• Women aged 45 years and older, under 21 years

Sponsors & Collaborators

• Lebanese University: lead

Study Sites (1)

Lebanese University, faculty of sciences III

Tripoli, North Lebanon, 961, Lebanon

Location

MeSH Terms

Conditions

Infertility, Female; Primary Ovarian Insufficiency; Polycystic Ovary Syndrome; Pregnancy, Ectopic; Salpingitis; Endometriosis; Leiomyoma; Uterine Anomalies; Endometritis; Infertility

Interventions

Chorionic Gonadotropin; Gonadotropins; Menotropins; Triptorelin Pamoate; LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; cetrorelix

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Ovarian Cysts; Cysts; Neoplasms; Pregnancy Complications; Fallopian Tube Diseases; Pelvic Inflammatory Disease; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Uterine Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Gonadotropins, Pituitary; Pituitary Hormones, Anterior; Pituitary Hormones; Biological Products; Complex Mixtures; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins

Study Officials

• Nehman Makdissy, Professor

  Lebanese University

  STUDY CHAIR

• Samar El Hamoui, Dr

  Lebanese University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: comparative protocols

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 28, 2019
• Study Start: February 1, 2018
• Primary Completion: August 22, 2019
• Study Completion: May 5, 2023
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)