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

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.