A Post Marketing Assessment of Gonal f Solution for Injection in a Prefilled Pen for Follicular Stimulation in in Vitro Fertilisation/Embryo Transfer (IVF-ET) Cycles
Condition: Infertility
MeSH terms: Infertility
Study type: Observational

Summary: 
      The development of recombinant DNA technology, culminated in the introduction of the first
      recombinant human follicle stimulating hormone (r hFSH), Gonal-f, which further developed to
      become Gonal-f Filled-by-Mass (FbM) pen has been used in the fertility treatment since many
      years. It has been found that subjects using the pen found it less stressful, easier to use
      and more convenient than a conventional syringe and would recommend the prefilled pen to
      another woman considering gonadotropin treatment. However, the use of the Gonal-f (FbM) pen
      between Serbian subjects is on a very low level though the Gonal f vials with the 75 IU of
      follitropin alfa have been present in Serbian market since 2003. On the contrary from the
      clinical practice in European countries, Serbian subjects usually receive daily dose of
      injectable gonadotropins at the IVF clinics or by partner/family member.

      This open-label, multicentric, observational non-interventional study is designed with the
      aim to know the reason of Serbian subjects not injecting themselves with Gonal f and the
      quality of life (QoL) of Serbian women/couples with the infertility problem.
    

Detailed description: 
      Fertility is the ability to conceive or induce conception. A normal fertile couple has about
      a 20% chance of achieving pregnancy in any one month of unprotected intercourse. Infertility
      is defined as the failure to conceive after 12 months of unprotected intercourse. It is
      generally estimated that about 10% to 15% of couples can be classified as having conception
      difficulties. About 30% of these are as a result of female factors, 30% as a result of male
      factors and a further 30% are due to a combination of both male and female factors. In about
      10% of cases, the underlying cause is not found (unexplained fertility).

      Follicle-stimulating hormone is one of the key hormones regulating reproductive functions
      both in females and males. In females, it stimulates the development of ovarian follicles
      which carry the oocytes, while in males it promotes spermatogenesis. Follicle-stimulating
      hormone binding to its receptor triggers intracellular mechanisms that regulate
      steroidogenesis, cell replication and expression of specific proteins and growth that
      modulate gametogenesis. Complete or partial deficiencies in FSH secretion are common causes
      of infertility in both women and men. Administration of FSH, either alone or in combination
      with luteinizing hormone (LH), has been used successfully to treat these infertility
      problems. Nearly 40% of women who are infertile have an ovulatory problem. These disorders
      may originate in the pituitary, the hypothalamus, the ovaries, or the anatomy of the
      reproductive system.

      Over the last 50 years the quality of FSH used in fertility treatment for inducing follicular
      development has improved via several distinguishable steps. For many years only human
      menopausal gonadotropin (hMG), a mixture of human LH and FSH extracted from the urine of
      post-menopausal women, was available for treatment of infertility. However, Merck Serono has
      developed the recombinant human FSH (r-hFSH) for clinical use, which has been in the market
      for several years. This development has been guided by the quest for control over the
      variability in urinary derived drugs. The recombinant system is a well-defined and controlled
      manufacturing process, which means that the content of these recombinant gonadotropins is
      consistent from batch-to-batch, accurately measured and filled-by-mass (i.e. in terms of
      weight in micrograms). This allows precise dosing control in both ovulation induction (OI)
      and assisted reproduction techniques (ART). Recombinant human fertility hormones are
      considered to have consistency of the source material and of the active product, the purity
      and specific activity of the protein, a good efficacy, safety and tolerability.

      OBJECTIVES

      Primary objective:

        -  To evaluate the ease-of-use of Gonal-f (FbM) in a prefilled pen in normal clinical
           practice conditions under different protocols of follicular stimulation

      Secondary objective:

        -  To evaluate the local tolerability (incidence of local reaction at the injection site)
           to drug administration.

      This study is planned to be conducted in 3 IVF/ART clinics in Serbia recruiting approximately
      20 subjects per centre (10 to each group) giving a total of 60 subjects. Subjects with
      previous stimulation treatment by the use of some injectable gonadotropins and not the
      stimulation with clomiphene citrate will be enrolled in this study. Depending on the kind of
      gonadotropin used in the previous stimulation treatment the subject has been treated with
      (meaning either Gonal-f ampules or urinary derived drugs), subjects will be stratified into
      two groups. The first group will include subjects who have undergone at least one treatment
      cycle with Gonal f powder and solvent for solution for injection within the past 12 months
      (equivalent to 75 IU/ml, 450 IU/0.75ml or 1050 IU/1.75 ml). The second group will include
      subjects which had undergone at least one treatment cycle with urine-derived FSH therapy with
      vials within the past 12 months. Subjects in both groups included in the study will be
      treated according to the Summary of Product Characteristics (SmPC) and according to clinical
      practice at each site. These subjects will also answer on questions from the first
      internationally validated QoL questionnaire called FertiQoL. The FertiQoL is the instrument
      that surveys infertile subjects to assess their QoL. Each and every subject will undergo one
      stimulation treatment cycle and each subject should be followed for approximately 2 weeks or
      until chemically proven pregnancy. After treatment, subject satisfaction with the Gonal f
      (FbM) prefilled pen will be measured using a post-treatment questionnaire in which
      participants will be asked to compare their treatment experiences and choose a preferred
      injection method.
    

Intervention name(s): Quality of Life Questionnaire (FertiQoL)
Intervention type(s): Other
Intervention description(s): Subjects will be administered the first internationally validated Quality of Life questionnaire (FertiQoL) to assess the quality of life of infertile subjects.
Other intervention name(s): FertiQoL
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pre-menopausal woman, between 18-43 years old requiring treatment with recombinant FSH for
        controlled ovarian hyperstimulation for IVF or OI in Serbia
      
Biospecimen description: 
      Plasma
    
Keywords: Ovulation Induction; Infertility; Gonal-f; FertiQoL; Quality of Life