Study to Evaluate if the Addition of r-hLH (Luveris®) to FSH From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing ART, Who Required High FSH Dose in a Previous Cycle
Condition: Reproductive Techniques, Assisted
MeSH terms: Infertility
Intervention: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH); r-hFSH
Intervention description: One r-hFSH and one r-hLH injection subcutaneously (s.c.) once daily during the treatment phase from Day 8 of stimulation until injection of human chorionic gonadotropin (hCG) or cancellation of the treatment cycle.; One r-hFSH injection s.c. once daily during the treatment phase from Day 8 of stimulation until injection of hCG or cancellation of the treatment cycle.
Intervention MeSH terms: Hormones; Follicle Stimulating Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 133.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: Reproductive Techniques, Assisted; Recombinant human follicle stimulating hormone (r-hFSH); Recombinant leutinizing hormone (r-hLH)

Summary:

      The present study was designed to investigate, in hyporesponder subjects, that required in a
      previous assisted reproductive technologies (ART) cycle follicle stimulating hormone (FSH)
      >3500 International Unit (IU), the possibility to decrease through recombinant human
      luteinizing hormone (r-hLH) supplementation, the FSH amount per oocytes retrieved and in the
      mean time to improve the overall cycle outcome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pre-menopausal infertile woman, aged 18 to 40 years inclusive, who wishes to conceive

          -  Regular, spontaneous menstrual cycle of 25-35 days

          -  Body mass index (BMI) ≤ 28

          -  FSH ≤ 10 IU/L (follicular phase, days 2-5)

          -  Prolactin (PRL) within the normal ranges

          -  Evidence of both ovaries by ultrasound scan

          -  Women undergoing IVF-Embryo Transfer (ET) or ICSI, down regulated with Gonadotropin
             releasing hormone analogues (GnRHa) (daily dose) under controlled ovarian
             hyperstimulation (COH) with FSH

          -  Washout > 90 days from last dose of clomiphene or gonadotrophin, before ongoing COH
             cycle

          -  Only one previous IVF-ET or ICSI cycle (in the last 9 months preceding the ongoing COH
             cycle) resulted in a hypo-response properly documented (from 6 to 12 oocytes with a
             total FSH dose ≥ 4000 IU)

          -  Negative pregnancy hCG test (urine or blood sample) before the ongoing COH cycles

          -  Willing and able to comply with the protocol for the duration of the study

          -  Written informed consent before applying any procedure related to the study protocol,
             which is not part of routine medical care, with the understanding that consent may be
             withdrawn by the subject at any time, without prejudice on their future medical care

        Exclusion Criteria:

          -  Oligo/Anovulatory cycles (World Health Organization [WHO] I and II)

          -  Male partner azoospermia (assessed within the last 12 months)

          -  Follicular phase (day 2-5) FSH > 10 IU/L even if only once observed in the medical
             history

          -  Abnormal cervical cytology (assessed within the last 12 months)

          -  History of unexplained gynecologic hemorrhage

          -  Any contraindication to pregnancy

          -  Known allergy to gonadotrophin

          -  Any clinically important systemic disease (e.g. insulin-dependent diabetes mellitus,
             epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular
             disease, serious corticoid-dependent asthma) which constitutes a contraindication to
             gonadotropin use

          -  Any medical condition which, according to the investigator's judgement, may affect the
             absorption, distribution, metabolism or excretion of the drug. In case of doubt,
             inclusion of the subject in question should be discussed with the Medical Responsible
             of Serono

          -  Known Human Immunodeficiency Virus (HIV) positivity

          -  Any substance abuse or history of drugs or alcohol abuse within the past 5 years

          -  Prior inclusion in the present study or simultaneous inclusion in a clinical study of
             another drug

          -  Refusal or inability to comply with the protocol