Infertility, Female, Luteinizing Hormone (LH)
Conditions
Keywords
Luteinizing Hormone, Long GnRH Agonist Protocol, Excessive LH Suppression, Controlled Ovarian Stimulation, In Vitro Fertilization, Embryo Quality
Brief summary
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.
Detailed description
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).
Interventions
DRUGRecombinant Luteinizing Hormone (rLH)
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.
DRUGGonadotropin-Releasing Hormone Agonist (GnRH-a)
Long-acting GnRH agonist (3.75 mg) administered subcutaneously on menstrual cycle day 2-4 for pituitary downregulation before controlled ovarian hyperstimulation.
Sponsors
Nanjing University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Not applicable. This is an open-label trial in which both participants and investigators are aware of the assigned interventions.
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to either the intervention group receiving exogenous luteinizing hormone (LH) supplementation in addition to the standard long GnRH agonist protocol, or the control group receiving the standard long GnRH agonist protocol without LH supplementation. Both groups will undergo controlled ovarian stimulation and in vitro fertilization (IVF) according to the study protocol.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 37 Years
Healthy volunteers
No
Inclusion criteria
* Women aged 20 to 37 years (inclusive). Diagnosed with infertility and undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the long-acting GnRH agonist protocol. Serum luteinizing hormone (LH) level \<0.5 U/L after pituitary downregulation. Normal uterine cavity as confirmed by hysteroscopy, sonohysterography, or hysterosalpingography within 6 months. Written informed consent provided prior to participation.
Exclusion criteria
* Polycystic ovary syndrome (PCOS). History of recurrent implantation failure (RIF). Presence of endometriosis or adenomyosis. History of ovarian surgery. Ovarian cysts ≥3 cm or with suspected malignancy. Poor ovarian reserve (antral follicle count \<5, anti-Müllerian hormone \<1.1 ng/mL, or baseline FSH \>10 IU/L). Chromosomal abnormalities in either partner. Systemic diseases such as uncontrolled hypertension, diabetes, thyroid disorders, or autoimmune diseases. Contraindications to ovarian stimulation medications or pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of cycles with no usable embryos | 7 days after oocyte retrieval | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total gonadotropin dose used | At the end of ovarian stimulation (average 8-12 days) | Cumulative dose (IU) of gonadotropins administered from stimulation start to trigger day. |
| Duration of gonadotropin stimulation | At the end of ovarian stimulation (average 8-12 days) | Number of days from gonadotropin initiation to trigger day. |
| Number of oocytes retrieved | At oocyte retrieval (36-38 hours after trigger) | Total number of oocytes collected during transvaginal ultrasound-guided oocyte retrieval. |
| Number of high-quality Day 3 embryos | 7 days after oocyte retrieval | Count of embryos meeting morphological criteria for high quality on Day 3 after fertilization, as determined by standard embryology scoring. |
| Early miscarriage rate | Within 12 weeks of gestation | Proportion of clinical pregnancies ending in miscarriage before 12 completed weeks of gestation. |
| Live birth rate | At delivery (up to 1 year after embryo transfer) | Proportion of embryo transfer cycles resulting in the delivery of at least one live-born infant. |
| Clinical pregnancy rate | 30 days after embryo transfer | Proportion of embryo transfer cycles resulting in at least one intrauterine gestational sac with fetal heartbeat, confirmed by transvaginal ultrasound. |
Countries
China
Contacts
Primary ContactYue Jiang, PhD
Backup ContactHui Zhang, PhD
Outcome results
None listed