Extended LH Administration

NCT06883890 | Not Yet Recruiting Phase 2

• 2 other identifiers: EC 174/20232022-004285-38
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief Summary

Luteinizing hormone (LH) plays an important role in follicular development, especially in the later stages of folliculogenesis. Theca interstitial cells and, later, granulosa cells express high concentrations of receptors for LH (LH-R). LH modulates the progressive remodeling and growth of the follicle . New evidence points to a role for LH in promoting ovarian follicle growth and maturation, even at very early stages of folliculogenesis. Studies analyzing LH-R expression profiles in the ovary have shown that LH-R is moderately expressed even in the smallest follicles, during what is known as the gonadotropin-independent phase . Immunohistochemical studies that examined the localization of LH-R in human follicles through different stages of follicular development reveal that LH-R is expressed by granulosa cells and some thecal cells in small pre-antral follicles LH promotes the transition of follicles to the antral stage, thus leading to an increase in functional ovarian reserve. Early follicular stages, particularly those between the primordial and pre-antral stages, are critical as they regulate the rate of follicle recruitment. The potential roles of LH in the early follicular phase were analyzed in a prospective, randomized multicenter study using a sequential approach to stimulation with recombinant human r-LH, followed by r-FSH, in women in hypogonadotropic hypogonadism because they were profoundly down-regulated by the administration of depo agonist GnRH analog. LH treatment was associated with an increase in small antral follicles before FSH stimulation and a higher number of normally fertilized embryos. In addition, AMH hormone was found to be significantly increased in both groups during the week prior to FSH stimulation These results seem to indicate that, if the reduction in the number of antral follicles is not due to a decrease in the number of primordial follicles, but to a slowing of progression, as in the case of women with long-standing hypothalamic amenorrhea, there may be room for a therapeutic approach. This is with the aim of improving the response to ovarian stimulation of the aforementioned patients who present with anovulatory cycles and in a condition of hypogonadotropic hypogonadism. A recent case series described two patients suffering from hypothalamic amenorrhea with very low levels of endogenous gonadotropins, and ovulatory factor infertility. These patients were treated with exogenous LH for one to two months (prolonged administration of LH). Increased levels of both AMH and AFC were demonstrated, and they responded adequately to ovarian stimulation. The purpose of this multicenter prospective randomized study follows recent publications confirming the implementation of ovarian reserve by supplementation with pretreatment with r-LH, a drug already on the market and routinely used in conventional controlled ovarian stimulation protocols. The aim is to confirm that pretreatment with rhLH at a dose of 185.5 IU/day for 60 days can improve ovarian reserve, as indicated by increased baseline AMH and AFC, compared with no pretreatment. The primary outcome is serum AMH value after treatment with r-LH and without. The planned duration of the study is 18 months, and a total of 84 patients are to be recruited. Patients will be randomized into two groups: group A who will receive pre-treatment with r-LH 185.5IU/day for 60 days and group B who will not receive pre-treatment. Patients will have a monitoring visit every two weeks for the duration of treatment, during which an ultrasound and blood sampling will be performed to evaluate the hormonal picture. Following pretreatment, a visit of with assessment of serum AMH and AFC value will be performed and the planned IVF cycle will be started. This will be followed by an additional final follow-up visit to collect obstetric and newborn outcomes that will be conducted by telephone

Conditions

Ovarian Reserve

Keywords

AMH; AFC; Ovarian reserve; LH

Outcome Measures

Primary Outcomes (1)

• Anti-Mullerian Hormone

  The primary endpoint of the study will be to confirm that the pre-treatment with rhLH at the dose of 187.5 IU/day for 60 days may improve ovarian reserve as indicated by an increase in basal AMH

  up to 18 months

Secondary Outcomes (1)

• Antral follicle count

  up to 18 months

Study Arms (2)

LH group

ACTIVE COMPARATOR

In the treatment group patients will receive the pretreatment with rLH, a daily dose of 187.5 IU (75 U in the morning and 112.5U in the evening) rLH treatment for 60 days will be administered

Drug: Recombinant LH (Luveris)

Control group

SHAM COMPARATOR

In the control group, women will not receive any therapy and will be followed up with the same schedule as women in the treatment group

Drug: No Treatment Added

Interventions

Recombinant LH (Luveris) DRUG

In the treatment group patients will receive the pretreatment with rLH, a daily dose of 187.5 IU (75 U in the morning and 112.5U in the evening) rLH treatment for 60 days will be administered.

LH group

No Treatment Added DRUG

In the control group, women will not receive any therapy and will be followed up with the same schedule as women in the treatment group

Control group

Eligibility Criteria

• Age: 25 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• AFC of at least 5 in the 3 months prior to the study cycle
• Basal AMH levels of at least 1 ng/ml in the 3 months prior to the study cycle
• Age 25-38 at the moment of the study cycle
• D3 Basal LH: 1-6 IU/L in the 3 months prior to the study cycle
• D3 Basal FSH: \< 8 IU/L in the 3 months prior to the study cycle 13
• D3 Estradiol \< 70 pg/ml in the 3 months prior to the study cycle
• Willing to participate
• Capable to understand and follow the study procedure
• eumenorrheic women with low LH levels candidate to IVF/ICSI cycle for tubal factor, male factor or for idiopathic infertility
• Acceptance and signature of the informed consent

You may not qualify if:

• PCOS patients according to Rotterdam's criteria
• Patients with irregular cycles (shorter than 25 days or longer than 35 days)
• Patients already treated with LH priming
• Patients planning to undergo duo/double stimulation
• Patients with ASRM Stage III or IV endometriosis
• Patients with prior surgery significantly affecting ovary (ie ovariectomy, cystectomy significantly reducing ovarian volume or others) as assessed by the responsible gynecologist
• Previous cycle with less than 4 oocytes recovered
• Patients treated with hormones in the 3 months before the study
• Patients with an already known endocrinological disease including hypothyroidism (defined by TSH \< 4 mIU/L), adrenocortical deficiency (ACTH stimulation test (250 mcg) with basal cortisol \<3 mcg or, if basal cortisol is 3-18 mcg serum level, cortisol serum level 30 minutes after the stimulation test \<18 mcg) and hyperprolactinemia (PLR \> 25mcg/l)
• previous episode of OHSS or exuberant ovarian response to gonadotropins
• hypersensitivity to the study drug
• contraindication for pregnancy
• porphyria or a family history of porphyria
• history of ovarian torsion
• BMI \> 30 kg/m2

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead

Related Publications (1)

• La Marca A, Longo M. Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series. Hum Reprod. 2022 Oct 31;37(11):2655-2661. doi: 10.1093/humrep/deac195.

  PMID: 36107111 BACKGROUND

MeSH Terms

Interventions

Luteinizing Hormone, beta Subunit

Intervention Hierarchy (Ancestors)

Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Antonio La Marca, MD, PhD

  University of Modena and Reggio Emilia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio La Marca, MD, PhD

CONTACT

+390594225862; antonio.lamarca@unimore.it

Maria Longo, MD

CONTACT

+390594225862; marialongo.d@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two-arm, multicenter, prospective, RCT (proof of concept) trial with two treatment arms at 2:1 ratio will involve couples attending an IVF/ICSI cycle, phase II study.

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 19, 2025
• Study Start: March 17, 2025
• Primary Completion: November 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 19, 2025

Record last verified: 2025-02