Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment

NCT06571214 | Not Yet Recruiting Phase 4

• 1 other identifier: MS700642_0020
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an exploratory, prospective, randomized, open-label and controlled trial to evaluate the potential benefit of r-hFSH:r-hLH 2:1 co-treatment starting from COS D1 versus r-hFSH alone in patients aged 35 to 40 under ovarian stimulation treatment. After signing informed consent form (ICF), all eligible participants will be randomly assigned in a 1:1 ratio to either treatment or control group, and GnRH antagonist protocol will be used in both treatment and control groups.

Conditions

Infertility

Keywords

recombinant human LH; recombinant human FSH; ovarian stimulation treatment; advanced maternal age population

Outcome Measures

Primary Outcomes (1)

• Good quality embryo rate (cleavage stage)

  Cleavage stage good-quality embryos are defined as embryos derived from normally fertilized zygotes with 7\~9 cells on day 3 post-fertilization, stage-specific cell size, less than 10% fragmentation, and no multinucleation. Cleavage stage good-quality embryo rate is defined as the number of cleavage stage good-quality embryos divided by the number of normally fertilized zygotes. Embryos will be assessed by two independent experienced embryologists to minimize intra-observation variability.

  Day 3 after fertilization

Secondary Outcomes (13)

• Number of oocytes

  24 hours after Oocytes pick up

• Number of MII oocytes (analyzed in ICSI subgroup only)

  24 hours after Oocytes pick up

• Total r-hFSH dose

  24 hours after ovulation triggering

• Fertilization rate

  24 hours after fertilization

• Blastocyst development rate

  5 days after fertilization, up to 7 days

Study Arms (2)

Treatment group

EXPERIMENTAL

The r-hFSH starting dose will be based on the patient's profile and physician's experience. r-hLH will be added at a ratio of 2:1 starting from day 1 of r-hFSH administration; the dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, and the r-hFSH: r-hLH dose will be 2:1, continuing to 24\~48 hours prior to trigger drug injection. For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians.

Drug: Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®); Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)

Control group

ACTIVE COMPARATOR

r-hFSH alone will be administrated for ovarian stimulation. The r-hFSH starting dose will be based on the patient's profile and physician's experience. The dose of r-hFSH during COS will be adjusted by the physician based on clinical experience and the patient's ovarian response, continuing to 24\~48 hours prior to trigger drug injection. For both groups, daily injection of 0.25 mg of cetrorelix (Cetrotide®, Merck Serono S.A.) will be administrated subcutaneously when at least one follicle with diameter ≥ 14 mm or serum LH level exceeds 10 IU/L or LH level is 2 folder than basal LH level or P level exceeds 0.8 ng/ml, continuing until ovulation triggering day. Cetrorelix can be administrated earlier in patients with advanced age or diminished ovarian reserve according to judgment of clinicians.

Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)

Interventions

Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) DRUG

As a r-hFSH agent, Gonal-f® is used for COS. It is a prefilled ready to use pen device containing follitropin alfa for injection and is designed for subcutaneous self-administration by patients undergoing COS for ART. It is available as dose presentations of 150 IU and 450 IU. The investigators and/or his/her delegate/s will explain the use of Gonal-f® prefilled pen. Gonal-f® will be prescribed by the investigator based on clinical diagnosis and treatment routines, and will not be provided free of charge.

Treatment group

Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) DRUG

This product is a white freeze-dried powder and a colorless and clear injection solvent, and stored away from light under 25℃ in the original packaging. Luveris® will be provided free of charge.

Control group; Treatment group

Eligibility Criteria

• Age: 35 Years - 40 Years
• Gender Eligibility Details: Patients aged 35 to 40 under ovarian stimulation treatment
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 35 to 40 (including 40)
• \<BMI\<28 kg/m2
• AFC up to 14
• First or second ART cycle
• Planned for ovarian stimulation with GnRH-antagonist for down-regulation
• Ejaculated sperm

You may not qualify if:

• Contraindications to ART treatment
• History of two or more spontaneous miscarriages
• History of two or more implantation failures after fresh or frozen-warmed embryo transfers
• Diagnosis of severe endometriosis
• Patients with endocrine and metabolic diseases (diabetes mellitus, hypogonadotropic amenorrhea, genital system tumors, hyperprolactinemia, etc.)
• Confirmed chromosomal abnormalities

Sponsors & Collaborators

• Nanjing University: lead

Study Sites (1)

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

MeSH Terms

Conditions

Infertility

Interventions

Injections; follitropin alfa; Luteinizing Hormone, beta Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Haiming Xia, Dr.

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haixiang Sun, Dr.

CONTACT

13851622008; stevensunz@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Reproductive Medicine Department

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 26, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): January 30, 2027
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)