Potential Benefit of r-hLH Addition in Patients Aged 35 to 40 Under Ovarian Stimulation Treatment
- Conditions
- Infertility
- Interventions
- Drug: Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®)Drug: Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®)
- Registration Number
- NCT06571214
- Lead Sponsor
- Nanjing University
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 300
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment group Recombinant Human Follitropin Alfa Solution for Injection (Gonal-f®) 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. Treatment group Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) 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. Control group Recombinant Human Lutropin alfa for Injection (r-hLH, Luveris®) 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.
- Primary Outcome Measures
Name Time Method Good quality embryo rate (cleavage stage) Day 3 after fertilization 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.
- Secondary Outcome Measures
Name Time Method Number of oocytes 24 hours after Oocytes pick up Number of oocytes is defined as the total number of oocytes obtained through transvaginal ultrasound guided puncture on the day of OPU. All follicles with an estimated diameter of ≥12 mm should be punctured.
Number of MII oocytes (analyzed in ICSI subgroup only) 24 hours after Oocytes pick up Number of MII oocyte is defined as the total number of an oocyte at metaphase of meiosis II, exhibiting the first polar body and with the ability to become fertilized
Total r-hFSH dose 24 hours after ovulation triggering Total r-hFSH dose is defined as the total dose of r-hFSH used for subcutaneous injection during COS period.
Fertilization rate 24 hours after fertilization * IVF normal fertilization rate is defined as the number of oocytes with 2PN and 2PB divided by the number of COCs inseminated.
* ICSI normal fertilization rate is defined as the number of oocytes with 2PN and 2PB divided by the number of MII oocytes injected.Blastocyst development rate 5 days after fertilization, up to 7 days Blastocyst development rate is defined as the proportion of blastocysts observed at 116 ± 2 h post-insemination as a function of the number of normally fertilized oocytes.
Clinical pregnancy rate (per transfer cycle and per oocyte retrieval cycle) At 4-6 weeks of amenorrhea after customized timing of embryo transfer Clinical pregnancy rate is defined as the number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. Clinical pregnancy is defined as the presence of gestational sac (intrauterine or ectopic) using ultrasound examination at 4\~6 weeks after embryo transfer.
Ongoing pregnancy rate At 12 weeks of amenorrhea after customized timing of embryo transfer Ongoing pregnancy rate is defined as the number of intrauterine pregnancies continued for 12 gestational weeks divided by the number of embryo transfer cycles.
Ovarian sensitivity index (OSI) 24 hours after fertilization OSI is defined as the total r-hFSH dose divided by the number of oocytes retrieved.
Follicular output rate (FORT) 24 hours after fertilization FORT is defined as the number of pre-ovulatory follicles (16\~22 mm) on the day of trigger divided by the AFC (3\~8 mm)
Follicle oocyte index (FOI) 24 hours after fertilization FOI is defined as the number of total oocytes retrieved divided by the AFC
Safety Assessments During the COS cycle (average cycle range 11 days), Up to 12 weeks after transfer AE, SAE and OHSS
Utilizable embryo rate 5 days after fertilization, up to 7 days Utilizable embryo rate is defined as the number of embryos (or blastocysts) suitable for transfer or cryopreservation as a function of the number of normally fertilized (2PN) oocytes observed on Day 1.
Implantation rate At 4-6 weeks of amenorrhea after customized timing of embryo transfer Implantation rate is defined as the number of gestational sacs observed divided by the number of embryos transferred using transvaginal ultrasound 4\~6 weeks after embryo transfer.
Trial Locations
- Locations (1)
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China