A Prospective Study to Evaluate the Addition of Subcutaneous Recombinant Human-Luteinizing Hormone With Recombinant Human-Follicle Stimulating Hormone on Follicular Development in Women Undergoing Ovarian Stimulation for Assisted Reproductive Technologies

NCT01121991 | Completed Phase 3 Results

• 1 other identifier: IMP 25244
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

In-vitro fertilization (IVF) of human oocytes followed by the replacement of embryo in the uterine cavity has become a well established treatment for female infertility attributable to damaged fallopian tubes, endometriosis or unexplained causes where alternative forms of therapy have failed. The most commonly used protocols of follicular stimulation now employs follicle stimulating hormone (FSH) and long-acting agonists of gonadotropin releasing hormone (GnRH) to prevent the occurrence of a mid-cycle luteinizing hormone (LH) surge and to ensure the induction of well-synchronized larger cohort of ovarian follicles. The results of a number of studies have demonstrated that in the majority of clinical situations, FSH administration alone is sufficient to achieve successful follicular development. A study had shown that in subjects receiving recombinant human-follicle stimulating hormone (r-hFSH) and recombinant human-luteinizing hormone (r-hLH), pregnancy rates were similar in the younger and older age groups, however, in women receiving r-hFSH alone, there was a significant decline in pregnancy rates for women 35 and older. This particular study also went on to show that the subgroup of women 35 and older, may benefit from supplementary r-hLH. A number of studies have been conducted to assess the safety and efficacy of r-hLH administered concomitantly with r-hFSH in the presence of developing follicles to reduce the rate of growth of intermediate and small follicles while allowing the dominant follicle to continue to progress. This was a Phase III, open-label, multicentre study to evaluate safety and efficacy of addition of Recombinant Human-Luteinizing Hormone (Luveris) to a standard assisted reproductive technologies (ART) protocol.

Conditions

Infertility; Ovarian Stimulation

Keywords

Infertility; Ovarian Stimulation; Luveris; Lutropin alpha; Controlled ovarian stimulation; Reproductive techniques, assisted

Outcome Measures

Primary Outcomes (2)

• Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI)

  Mean number of metaphase II oocytes was calculated for each participant undergoing ovum pick up for ICSI. ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.

  On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration).

• Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF)

  Mean number of oocytes undergoing ovum pick up for IVF were calculated for each participant. IVF is a process by which egg cells are fertilized by sperm outside the body, in-vitro.

  On the day of ovum pick up (Day 1 or 2 after hCG administration).

Secondary Outcomes (6)

• Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up

  On day of ovum pick up (Day 1 or 2 after hCG administration)

• Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies

  Post-hCG days 15-20 and post-hCG days 35-42.

• Number of Participants With Multiple Pregnancies

  Post-hCG Day 35-42.

• Number of Live Births

  Post-hCG days 15-20 to pregnancy follow up.

• Pregnancy Loss Per Clinical Pregnancy

  Post-hCG days 35-42.

Interventions

Recombinant Human-Luteinizing Hormone (Luveris) DRUG

Recombinant Human-Luteinizing Hormone (Luveris) was administered once daily subcutaneously at a starting dose of 150 IU per day beginning on stimulation Day 6.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female subjects who underwent ovarian stimulation for ART (IVF/ICSI) using r-hFSH.
• Subjects who in the opinion of the treating investigator met any of the following criteria to require r-LH supplementation during the ovarian stimulation:
• were selected for a GnRH agonist protocol to induce pituitary desensitization
• previous poor ovarian response to r-hFSH alone
• aged 35 to 40 years
• elevated baseline hormone parameters that were predictive of poor ovarian response
• Female subjects aged between 18-40 years
• Subjects with uterine cavity able to sustain embryo implantation or pregnancy
• Subject who had no known infection with human immunodeficiency virus, hepatitis B or C virus
• Subjects who were willing to participate and comply with the protocol for the duration of the study
• Subjects who had given informed consent, prior to any study-related procedure not part of normal medical care

You may not qualify if:

• Subjects with clinically significant systemic disease (e.g. insulin-dependent diabetes, epilepsy, severe migraine, intermittent porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)
• Any contraindication to being pregnant and/or carrying a pregnancy to term
• Subjects with abnormal gynecological bleeding of undetermined origin
• Subjects with known allergy to gonadotrophin preparations
• Subjects with any medical condition for which the use of gonadotrophin preparations was contraindicated
• Subjects who had previously entered into this study or simultaneously participated in another clinical drug trial
• Subjects with any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
• Subjects who had refused or were unable to comply with protocol

Sponsors & Collaborators

• EMD Serono: lead

MeSH Terms

Conditions

Infertility; Helping Behavior

Interventions

Luteinizing Hormone, beta Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Social Behavior; Behavior

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

Results Point of Contact

• Title: Medical Responsible
• Organization: EMD Serono Canada Inc., an affiliate of Merck KGaA, Darmstadt, Germany

david.sciberras@emdserono.com

+1-888-737-6668

Study Officials

• Medical Responsible

  EMD Serono Canada Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 10, 2010
• First Posted: May 12, 2010
• Study Start: September 1, 2004
• Primary Completion: September 1, 2005
• Last Updated: August 7, 2013
• Results First Posted: March 18, 2011

Record last verified: 2013-08