A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve
Condition: Infertility; Ovulation Induction
MeSH terms: Infertility
Intervention: Recombinant human follicle stimulating hormone (r-hFSH); Recombinant human luteinizing hormone (r-hLH)
Intervention description: Subjects will receive subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day [mg/day]).; Subjects will receive subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation.
Intervention MeSH terms: Hormones; Follicle Stimulating Hormone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: Female
Minimum age: 35 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Reproductive technology, Assisted; Recombinant human follicle stimulating hormone (r-hFSH); Recombinant leutinizing hormone (r-hLH); Ovulation induction; Infertility

Summary:

      This was a prospective, randomized, Phase II, comparative study with a parallel control for
      evaluating the efficacy and safety of combined treatment of recombinant human follicle
      stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH). The combined
      treatment was administered at the middle of the follicular phase in subjects undergoing
      in-vitro fertilisation (IVF) through intracytoplasmic sperm injection (ICSI) and transfer of
      embryos (ET).
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects must meet the following inclusion criteria within the 6 months prior to
        starting the pituitary suppression unless otherwise specified:

          -  Postmenopausal woman aged between 35 and 40 years that wishes to become pregnant

          -  Subjects with basal serum level (beginning of the follicular phase, Day 2-5) of
             Follicle-Stimulating Hormone (FSH) less than 10 IU/L determined within the 6 months
             prior as well as Luteinizing hormone (LH) and Estradiol (E2) levels within the normal
             interval according to standard data for the area where the study was carried out

          -  Subjects with a regular menstrual cycles between 25-35 days

          -  Subjects with infertility that justifies treatment with IVF/ET or ICSI

          -  Subjects undergoing controlled ovarian stimulation (COS) with r-hFSH using a long
             protocol with GnRH-a

          -  Sperm availability from the subject's current partner unless it is planned to use
             sperm from a donor

          -  Subjects with both ovaries

          -  Subjects with uterine cavity capable of withstanding the implantation of the embryo
             and pregnancy

          -  Subjects whose vaginal smear (PAP) was normal within the 3 years prior to starting the
             stimulation

          -  Subjects with body mass index (BMI) between 18 and 30 at the time of participation in
             the study

          -  Subjects in whom at least 30 days have elapsed since the last dose of clomiphene
             citrate or gonadotropins before beginning treatment with GnRH-a

          -  Subjects with a negative pregnancy test result using the beta human chorionic
             gonadotropin (beta-hCG) test (in urine or blood) before beginning treatment with
             GnRH-a

          -  Subjects willing to and capable of following the protocol during the entire study

          -  Subjects who have provided informed written consent before carrying out any procedure
             related with the study (that is not part of the normal medical treatment followed by
             the subject)

        Exclusion Criteria:

          -  Subject who were human immunodeficiency virus, hepatitis B and C virus positive

          -  Subjects suffering from any clinically important systematic disease, hypothalmic or
             pituitary tumour, ovarian, uterine or breast cancer, endocrinopathy and/or medical
             alterations, biochemical or hematological that as per the investigators judgement, may
             interfere with the gonadotropin treatment

          -  Subjects who have been subjected to more than 2 assisted reproductive cycles in the
             past

          -  Subjects who have cancelled 2 cycles in the past

          -  Subjects who have cryopreserved embryos from previous assisted reproductive cycles

          -  Subjects with non explained vaginal haemorrhages

          -  Subjects with polycystic ovary, enlarged ovary or ovarian cysts of unknown aetiology

          -  Subjects with any contraindication for getting pregnant or taking the pregnancy to
             full term

          -  Subjects with known allergy to the gonadotropin preparations or any of its excipients

          -  Subjects with current drug use or prior personal history of alcohol, drug or
             psychiatric drug dependency in the past five years

          -  Subjects with prior participation in this study or simultaneous participation in a
             different clinical study with a medication under investigation

          -  Subjects who were not willing to or incapable of following the study protocol