Clinical trial NCT06571214: Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
Official title: An Exploratory, Randomized, Open-label, Controlled Study to Evaluate the Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Infertility
Keywords: recombinant human LH
recombinant human FSH
ovarian stimulation treatment
advanced maternal age population
Lead sponsor: Nanjing University
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 300
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

1. Treatment group: 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.
2. Control group: 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.

The estimated treatment duration is 11 days from the first day of COS until 24\~48 h prior to trigger drug injection, and this may vary depending on individual circumstances.

Follicular development, serum E2 and P levels will be monitored during COS according to the investigator site's ART practice until the criteria to administer trigger drug are met to induce final oocyte maturation. Trigger drug administration is to be performed according to the site's routine clinical practice.

Oocyte pick-up (OPU), IVF/ICSI, ET, and luteal phase support (LPS) will be performed according to the site's routine practice. LPS will be started after oocyte retrieval in fresh embryo transfer.

Eligibility criteria: Inclusion Criteria:

* Age 35 to 40 (including 40)
* 18.5\<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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Good quality embryo rate (cleavage stage)
timeFrame: Day 3 after fertilization
Secondary outcomes:
measure: Number of oocytes
timeFrame: 24 hours after Oocytes pick up
measure: Number of MII oocytes (analyzed in ICSI subgroup only)
timeFrame: 24 hours after Oocytes pick up
measure: Total r-hFSH dose
timeFrame: 24 hours after ovulation triggering
measure: Fertilization rate
timeFrame: 24 hours after fertilization
measure: Blastocyst development rate
timeFrame: 5 days after fertilization, up to 7 days
measure: Utilizable embryo rate
timeFrame: 5 days after fertilization, up to 7 days
measure: Implantation rate
timeFrame: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
measure: Clinical pregnancy rate (per transfer cycle and per oocyte retrieval cycle)
timeFrame: At 4-6 weeks of amenorrhea after customized timing of embryo transfer
measure: Ongoing pregnancy rate
timeFrame: At 12 weeks of amenorrhea after customized timing of embryo transfer
measure: Ovarian sensitivity index (OSI)
timeFrame: 24 hours after fertilization
measure: Follicular output rate (FORT)
timeFrame: 24 hours after fertilization
measure: Follicle oocyte index (FOI)
timeFrame: 24 hours after fertilization
measure: Safety Assessments
timeFrame: During the COS cycle (average cycle range 11 days), Up to 12 weeks after transfer
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Haiming Xia, Dr.
role: PRINCIPAL_INVESTIGATOR
References: