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
Condition: Infertility; Ovarian Stimulation
MeSH terms: Infertility
Intervention: Recombinant Human-Luteinizing Hormone (Luveris)
Intervention description: Recombinant Human-Luteinizing Hormone (Luveris) was administered once daily subcutaneously at a starting dose of 150 IU per day beginning on stimulation Day 6.
Intervention MeSH terms: Hormones
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Infertility; Ovarian Stimulation; Luveris; Lutropin alpha; Controlled ovarian stimulation; Reproductive techniques, assisted

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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