Recombinant Follicle Stimulating Hormone (FSH) (Gonal-f®): Use in Ovulation Induction
Condition: Ovulation Induction
Intervention: Recombinant FSH (follitropin alpha)
Intervention description: A starting dose of 75 IU and a first adjustment on Day 14 or Day 7 of stimulation in Group I and II respectively, if no ovarian response is observed.
Intervention MeSH terms: Follicle Stimulating Hormone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 310.0
Sex: Female
Minimum age: 18 Years
Maximum age: 37 Years
Healthy volunteers: No
Keywords: Infertility; Ovulation induction; Gonal-f; Follitropin alpha; Polycystic ovarian syndrome; Anovulatory infertility

Summary:

      This is an open-label, prospective, randomized, controlled, multicentric, multinational,
      phase IV study to evaluate the use of Gonal-f in inducing ovulation in female subjects with
      chronic anovulation. It has been observed that conventional high dose set up regimen of
      gonadotropin and human chorionic gonadotropin (hCG) is effective in anovulatory subjects in
      terms of overall pregnancy rates. However, development of multiple follicles leading to
      multiple pregnancy and/or ovarian hyperstimulation syndrome (OHSS) is the major complications
      associated with this high dose set up. Chronic low-dose (CLD) protocols of follicle
      stimulating hormone (FSH), aimed at finding the threshold amount of FSH necessary to promote
      monofolliculogenesis, have been found to be successful in reducing the rate of OHSS almost to
      nil and the rate of multiple pregnancies to a minimum. This post-marketing study will
      investigate tailoring of recombinant follicle stimulating hormone (r-FSH) in a large
      population (N=310) of subjects from a region (North Africa/Middle East) that has not been
      included in previous studies of ovulation induction in subjects with chronic anovulation. The
      study aims to increase current knowledge of the efficacy and safety of Gonal-f, and provide
      fertility physicians with experience in Gonal-f treatment in anovulatory infertility, thereby
      contributing to the development of FSH dosing guidelines for ovulation induction by defining
      the optimal CLD and Low dose (LD) regimens.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Premenopausal female subjects, aged between 18 and 37 years inclusive

          -  Subjects willing to conceive

          -  Subjects who are infertile due to chronic anovulation demonstrated by a cycle duration
             of > 35 days, or regular cycles with progesterone (P4) levels < 1 nanomole/milliliter
             (nmol/mL) during luteal phase (Day 25)

          -  Subjects who have experienced spontaneous menses, menses induced by clomiphene citrate
             therapy, or a positive progestin-induced withdrawal within the previous year

          -  Subjects with FSH and PRL serum values within the normal range in the early follicular
             phase

          -  Subjects with total antral follicle count (AFC) > 10 (of follicle size ≥ 2 mm and < 11
             mm) in both ovaries

          -  Subjects with at least 1 patent tube, as documented by recent (within 2 years before
             treatment assignment) hysterosalpingography (HSG)

          -  Subjects with normal uterine cavity, as documented by recent (within 2 years before
             treatment assignment) hysteroscopy, HSG or ultrasound scan

          -  Subjects with body mass index (BMI) >20 and ≤32 kilogram square per meter (kg/m^2)

          -  Subjects with negative cervical Papanicolaou (PAP) test within the 6 months prior to
             screening

          -  Male partners of female subjects with sperm compatible with non assisted fertilization

          -  Subjects who are willing and able to participate in the study and have provided
             written, informed consent

        Exclusion Criteria:

          -  Subjects with history of hypersensitivity to the active substance follitropin alpha,
             FSH, or to any of the excipients of Gonal-f

          -  Subjects with ovarian enlargement or ovarian cyst unrelated to PCOS, and of unknown
             origin on ultrasound

          -  Subjects with evidence of diminished ovarian reserve (cycle length < 26 days; FSH
             above the upper limit of local serum FSH values, total AFC in both ovaries < 10)

          -  Subjects with myomatous uterus, which in the opinion of the investigator could impair
             pregnancy evolution

          -  Subjects who have undergone 3 or more previous miscarriages

          -  Subjects with any previous extrauterine pregnancy

          -  Pregnant or lactating female subjects

          -  Subjects with abnormal gynecological bleeding of unknown etiology

          -  Subjects with previous history of severe OHSS

          -  Subjects who have undergone operative pelvic surgery which could induce mechanical
             infertility (e.g tubes blockage) or pelvic inflammatory disease (PID) before treatment
             assignment excluding curettage and hysteroscopy

          -  Subjects with tumors of the hypothalamus and pituitary gland

          -  Subjects with ovarian, uterine or mammary carcinoma

          -  Subjects treated with clomiphene citrate or gonadotropins within 1 month of the
             screening evaluation

          -  Subjects with any medical condition which, in the opinion of the investigator, would
             prevent an effective response, such as primary ovarian failure, or malformations of
             the reproductive organs incompatible with pregnancy

          -  Subjects with any medical condition which, in the opinion of the investigator, may
             interfere with the absorption, distribution, metabolism or excretion of the drug

          -  Subjects with any clinically significant systemic disease (e.g. insulin-dependent
             diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to
             term; also including subjects with non insulin dependent diabetes mellitus (NIDDM)

          -  An active substance abuser

          -  Subjects with known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or
             C virus in the trial subject or her male partner

          -  Subjects who have simultaneously participated in another clinical trial