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

NCT ID: NCT07128394

Last Updated: 2025-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

590 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-01

Study Completion Date

2026-11-30

Brief Summary

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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

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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).

Conditions

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Infertility, Female Luteinizing Hormone (LH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Not applicable. This is an open-label trial in which both participants and investigators are aware of the assigned interventions.

Study Groups

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Recombinant LH Supplementation Group

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.

Group Type EXPERIMENTAL

Recombinant Luteinizing Hormone (rLH)

Intervention Type DRUG

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 Follicle-Stimulating Hormone (rFSH)

Intervention Type DRUG

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.

Gonadotropin-Releasing Hormone Agonist (GnRH-a)

Intervention Type DRUG

Long-acting GnRH agonist (3.75 mg) administered subcutaneously on menstrual cycle day 2-4 for pituitary downregulation before controlled ovarian hyperstimulation.

Conventional rFSH-Only Group

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.

Group Type ACTIVE_COMPARATOR

Recombinant Follicle-Stimulating Hormone (rFSH)

Intervention Type DRUG

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.

Gonadotropin-Releasing Hormone Agonist (GnRH-a)

Intervention Type DRUG

Long-acting GnRH agonist (3.75 mg) administered subcutaneously on menstrual cycle day 2-4 for pituitary downregulation before controlled ovarian hyperstimulation.

Interventions

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Recombinant 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.

Intervention Type DRUG

Recombinant Follicle-Stimulating Hormone (rFSH)

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.

Intervention Type DRUG

Gonadotropin-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.

Intervention Type DRUG

Other Intervention Names

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lutropin alfa Luveris follitropin alfa Gonal-F triptorelin Diphereline

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Nanjing University

OTHER

Sponsor Role lead

Responsible Party

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Li-jun Ding

Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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慧 Jiang, PhD

Role: PRINCIPAL_INVESTIGATOR

Nanjing Drum Tower Hospital: Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital

Locations

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Nanjing Drum Tower Hospital, Nanjing University Medical School

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yue Jiang, PhD

Role: CONTACT

+8613814122872

Hui Zhang, PhD

Role: CONTACT

+8618262637731

Facility Contacts

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Yue Jiang, PhD

Role: primary

+8613814122872

Hui Zhang, PhD

Role: backup

+8618262637731

References

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Yazici Yilmaz F, Gorkemli H, Colakoglu MC, Aktan M, Gezginc K. The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation. Gynecol Endocrinol. 2015 Feb;31(2):141-4. doi: 10.3109/09513590.2014.965675. Epub 2014 Sep 19.

Reference Type BACKGROUND
PMID: 25237892 (View on PubMed)

Tesarik J, Mendoza C. Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod. 2002 Dec;17(12):3129-37. doi: 10.1093/humrep/17.12.3129.

Reference Type BACKGROUND
PMID: 12456612 (View on PubMed)

Wu KK, Papp AC, Manner CE, Hall ER. Interaction between lymphocytes and platelets in the synthesis of prostacyclin. J Clin Invest. 1987 Jun;79(6):1601-6. doi: 10.1172/JCI112995.

Reference Type BACKGROUND
PMID: 3108319 (View on PubMed)

Kan O, Simsir C, Atabekoglu CS, Sonmezer M. The impact of adding hp-hMG in r-FSH started GnRH antagonist cycles on ART outcome. Gynecol Endocrinol. 2019 Oct;35(10):869-872. doi: 10.1080/09513590.2019.1600667. Epub 2019 Apr 11.

Reference Type BACKGROUND
PMID: 30973022 (View on PubMed)

Propst AM, Hill MJ, Bates GW, Palumbo M, Van Horne AK, Retzloff MG. Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration. Fertil Steril. 2011 Oct;96(4):898-904. doi: 10.1016/j.fertnstert.2011.06.069. Epub 2011 Aug 11.

Reference Type BACKGROUND
PMID: 21839437 (View on PubMed)

Tayyar AT, Kahraman S. Comparison between cycles of the same patients when using recombinant luteinizing hormone + recombinant follicle stimulating hormone (rFSH), human menopausal gonadotropin + rFSH and rFSH only. Arch Med Sci. 2019 May;15(3):673-679. doi: 10.5114/aoms.2017.72408. Epub 2018 Jan 8.

Reference Type BACKGROUND
PMID: 31110533 (View on PubMed)

Fleming R, Rehka P, Deshpande N, Jamieson ME, Yates RW, Lyall H. Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH. Hum Reprod. 2000 Jul;15(7):1440-5. doi: 10.1093/humrep/15.7.1440.

Reference Type BACKGROUND
PMID: 10875848 (View on PubMed)

Westergaard LG, Laursen SB, Andersen CY. Increased risk of early pregnancy loss by profound suppression of luteinizing hormone during ovarian stimulation in normogonadotrophic women undergoing assisted reproduction. Hum Reprod. 2000 May;15(5):1003-8. doi: 10.1093/humrep/15.5.1003.

Reference Type BACKGROUND
PMID: 10783342 (View on PubMed)

Alviggi C, Clarizia R, Mollo A, Ranieri A, De Placido G. Outlook: who needs LH in ovarian stimulation? Reprod Biomed Online. 2006 May;12(5):599-607. doi: 10.1016/s1472-6483(10)61186-8.

Reference Type BACKGROUND
PMID: 16790105 (View on PubMed)

Li F, Ye T, Kong H, Li J, Hu L, Jin H, Su Y, Li G. Efficacies of different ovarian hyperstimulation protocols in poor ovarian responders classified by the POSEIDON criteria. Aging (Albany NY). 2020 May 29;12(10):9354-9364. doi: 10.18632/aging.103210. Epub 2020 May 29.

Reference Type BACKGROUND
PMID: 32470947 (View on PubMed)

Other Identifiers

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BJHPA-2023-SZHYXZHQN-006

Identifier Type: OTHER

Identifier Source: secondary_id

SZ-ELH-2025

Identifier Type: -

Identifier Source: org_study_id

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