Extra Luteinizing Hormone Improve Embryo Quality in IVF Patients With Low LH During Long GnRH-Agonist Treatment (ELH-IVF)

Nanjing University

Status: Enrolling

Conditions: Luteinizing Hormone (LH); Infertility, Female

Treatments: Drug: Gonadotropin-Releasing Hormone Agonist (GnRH-a); Drug: Recombinant Luteinizing Hormone (rLH); Drug: Recombinant Follicle-Stimulating Hormone (rFSH)

Study type: Interventional

Funder types: Other

Identifiers

NCT07128394

BJHPA-2023-SZHYXZHQN-006 (Other Identifier)

SZ-ELH-2025

Details and patient eligibility

About

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.

Full 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).

Enrollment: 590 estimated patients

Sex: Female

Ages: 20 to 37 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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590 participants in 2 patient groups

Recombinant LH Supplementation Group

Experimental group

Description:

Participants receive controlled ovarian hyperstimulation (COH) using a long-acting GnRH agonist (triptorelin 3.75 mg) for pituitary downregulation, followed by recombinant FSH (rFSH) combined with recombinant LH (rLH) at a ratio of 2:1 starting on stimulation day. rLH administration continues throughout the stimulation phase, with gonadotropin doses adjusted based on follicular growth and hormone monitoring. Trigger is given when 2-3 leading follicles reach ≥18 mm, followed by oocyte retrieval, IVF/ICSI, and embryo quality assessment.

Treatment:

Drug: Recombinant Follicle-Stimulating Hormone (rFSH)

Drug: Recombinant Luteinizing Hormone (rLH)

Drug: Gonadotropin-Releasing Hormone Agonist (GnRH-a)

Conventional rFSH-Only Group

Active Comparator group

Description:

Participants receive the same long-acting GnRH agonist downregulation and rFSH stimulation protocol as the experimental arm, but without rLH supplementation. Only rFSH is used during COH, with dose adjustments according to follicular development and hormone levels. Trigger, oocyte retrieval, IVF/ICSI, and embryo assessment follow the same procedures as in the experimental arm.

Treatment:

Drug: Recombinant Follicle-Stimulating Hormone (rFSH)

Drug: Gonadotropin-Releasing Hormone Agonist (GnRH-a)