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

NCT07128394 | Recruiting

• 2 other identifiers: SZ-ELH-2025BJHPA-2023-SZHYXZHQN-006
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility, Female; Luteinizing Hormone (LH)

Keywords

Luteinizing Hormone; Long GnRH Agonist Protocol; Excessive LH Suppression; Controlled Ovarian Stimulation; In Vitro Fertilization; Embryo Quality

Outcome Measures

Primary Outcomes (1)

• Proportion 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.

  7 days after oocyte retrieval

Secondary Outcomes (7)

• Number of high-quality Day 3 embryos

  7 days after oocyte retrieval

• Total gonadotropin dose used

  At the end of ovarian stimulation (average 8-12 days)

• Duration of gonadotropin stimulation

  At the end of ovarian stimulation (average 8-12 days)

• Number of oocytes retrieved

  At oocyte retrieval (36-38 hours after trigger)

• Clinical pregnancy rate

  30 days after embryo transfer

Study Arms (2)

Recombinant LH Supplementation Group

EXPERIMENTAL

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.

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

Conventional rFSH-Only Group

ACTIVE COMPARATOR

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.

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

Interventions

Recombinant Luteinizing Hormone (rLH) 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.

Also known as: lutropin alfa, Luveris

Recombinant LH Supplementation Group

Recombinant Follicle-Stimulating Hormone (rFSH) 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.

Also known as: follitropin alfa, Gonal-F

Conventional rFSH-Only Group; Recombinant LH Supplementation Group

Gonadotropin-Releasing Hormone Agonist (GnRH-a) DRUG

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

Also known as: triptorelin, Diphereline

Conventional rFSH-Only Group; Recombinant LH Supplementation Group

Eligibility Criteria

• Age: 20 Years - 37 Years
• Gender Eligibility Details: Eligibility is limited to biological females of reproductive age due to the study's focus on ovarian stimulation and embryo quality in IVF/ICSI cycles.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanjing University: lead

Study Sites (1)

Nanjing Drum Tower Hospital, Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

Related Publications (10)

• 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.

  PMID: 25237892 BACKGROUND

• 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.

  PMID: 12456612 BACKGROUND

• 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.

  PMID: 3108319 BACKGROUND

• 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.

  PMID: 30973022 BACKGROUND

• 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.

  PMID: 21839437 BACKGROUND

• 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.

  PMID: 31110533 BACKGROUND

• 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.

  PMID: 10875848 BACKGROUND

• 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.

  PMID: 10783342 BACKGROUND

• 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.

  PMID: 16790105 BACKGROUND

• 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.

  PMID: 32470947 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Luteinizing Hormone; Luteinizing Hormone, beta Subunit; Glycoprotein Hormones, alpha Subunit; follitropin alfa; Gonadotropin-Releasing Hormone; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Chorionic Gonadotropin; Follicle Stimulating Hormone; Thyrotropin; Placental Hormones; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• 慧 Jiang, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yue Jiang, PhD

CONTACT

+8613814122872; jiangyue85@163.com

Hui Zhang, PhD

CONTACT

+8618262637731; hellozhanghui@sina.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Not applicable. This is an open-label trial in which both participants and investigators are aware of the assigned interventions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

Model Details: 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.

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 19, 2025
• Study Start: February 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)