This randomized controlled trial aims to evaluate whether supplementation with exogenous luteinizing hormone (LH) can improve embryo quality in patients undergoing in vitro fertilization (IVF) with a long gonadotropin-releasing hormone agonist (GnRH-a) protocol who have excessive suppression of LH. Eligible participants will be randomly assigned to receive either exogenous LH supplementation or standard care. The primary outcome is embryo quality, and secondary outcomes include pregnancy rates and safety assessments. The study is conducted at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University.
Excessive suppression of luteinizing hormone (LH) during ovarian stimulation with a long gonadotropin-releasing hormone agonist (GnRH-a) protocol has been associated with suboptimal follicular development, impaired oocyte maturation, and reduced embryo quality. LH plays a critical role in the final stages of folliculogenesis, steroidogenesis, and ovulation, and its deficiency during controlled ovarian hyperstimulation may adversely affect the developmental competence of oocytes. This randomized controlled trial is designed to evaluate whether supplementation with exogenous LH can improve embryo quality in patients undergoing in vitro fertilization (IVF) with excessive LH suppression during a long GnRH-a protocol. Eligible participants are women meeting predefined hormonal suppression criteria prior to or during stimulation. Participants will be randomly assigned to receive either exogenous LH supplementation in addition to standard ovarian stimulation or standard care without LH supplementation. The primary endpoint is the proportion of high-quality embryos obtained per cycle. Secondary endpoints include clinical pregnancy rate, implantation rate, live birth rate, and safety outcomes such as incidence of ovarian hyperstimulation syndrome (OHSS) and adverse events. The study aims to provide high-quality evidence to guide the optimal management of patients with profound LH suppression during controlled ovarian stimulation. Findings from this trial may contribute to refining stimulation protocols and improving reproductive outcomes in assisted reproductive technology (ART).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
590
Recombinant LH administered subcutaneously in combination with recombinant FSH (rFSH) at a ratio of 2:1 starting on stimulation day, continued throughout controlled ovarian hyperstimulation. Dosage adjusted according to follicular growth and serum hormone levels.
Recombinant FSH administered subcutaneously for controlled ovarian hyperstimulation after pituitary downregulation with a long-acting GnRH agonist. Dosage adjusted based on follicular development and hormone monitoring.
Long-acting GnRH agonist (3.75 mg) administered subcutaneously on menstrual cycle day 2-4 for pituitary downregulation before controlled ovarian hyperstimulation.
Nanjing Drum Tower Hospital, Nanjing University Medical School
Nanjing, Jiangsu, China
RECRUITINGProportion of cycles with no usable embryos
The number of IVF/ICSI cycles with no transferable embryos divided by the total number of oocyte retrieval cycles, evaluated based on embryo morphology and grading on Day 3 or Day 5-6 after fertilization.
Time frame: 7 days after oocyte retrieval
Number of high-quality Day 3 embryos
Count of embryos meeting morphological criteria for high quality on Day 3 after fertilization, as determined by standard embryology scoring.
Time frame: 7 days after oocyte retrieval
Total gonadotropin dose used
Cumulative dose (IU) of gonadotropins administered from stimulation start to trigger day.
Time frame: At the end of ovarian stimulation (average 8-12 days)
Duration of gonadotropin stimulation
Number of days from gonadotropin initiation to trigger day.
Time frame: At the end of ovarian stimulation (average 8-12 days)
Number of oocytes retrieved
Total number of oocytes collected during transvaginal ultrasound-guided oocyte retrieval.
Time frame: At oocyte retrieval (36-38 hours after trigger)
Clinical pregnancy rate
Proportion of embryo transfer cycles resulting in at least one intrauterine gestational sac with fetal heartbeat, confirmed by transvaginal ultrasound.
Time frame: 30 days after embryo transfer
Early miscarriage rate
Proportion of clinical pregnancies ending in miscarriage before 12 completed weeks of gestation.
Time frame: Within 12 weeks of gestation
Live birth rate
Proportion of embryo transfer cycles resulting in the delivery of at least one live-born infant.
Time frame: At delivery (up to 1 year after embryo transfer)
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