Anti-Mullerian Hormone (AMH) Versus Antral Follicle Count (AFC) Guided rFSH Dosing Study

A Phase IV, Open-label 2 Arm Trial to Compare the Efficacy and Safety of a Pre-defined Dose of GONAL-f® Based on Antral Follicle Count [Follicles ≥2mm - <11mm]), or AMH for Ovarian Stimulation in Subjects Undergoing Assisted Reproductive Technology (ART) Treatment.

The overall objectives of this trial are to: To explore the efficacy and safety of using either antral follicle count (AFC) or anti-Mullerian hormone (AMH) to guide the starting dose of GONAL-f® in ovarian stimulation for Assisted Reproductive Technology (ART). To assess the differences in both ovarian response and clinical pregnancy rate between subjects with different AFC and AMH levels undergoing ART.

Trial design This trial is a prospective, Phase IV 2 arm trial exploring the efficacy and safety of using either AFC or AMH to guide the starting GONAL-f® dose for the stimulation treatment of subjects undergoing ART. Throughout the trial period and before the start of a routine ART cycle, investigators will propose the trial to their potential subjects. All subjects who agree to participate in the trial must sign a consent form, irrespective of whether or not they ultimately agree to have their dose determined by the study protocol. Eligible subjects will be randomised in blocks of 4 at each site via a computer generated random number list to either the AFC guided arm (control) or the AMH guided arm (treatment). The starting doses of GONAL-f® for each arm will be based on the study algorithms, using AFC or AMH guidance. The investigator will then enter initiate ovarian stimulation with an individualised GONAL-f® dose for that specific subject. This will be maintained for the first 5 days of stimulation after which the dose can be modified based on investigator decision and in accordance with the site's routine clinical practice. Trial Population Female partners of infertile couples requiring Assisted Reproductive Technology (ART) treatment. Data Analysis and Statistics The primary end-point proportion of patients with desired number of retrieved oocytes (8-12) will be compared between the 2 arms using the chi -square test. The null hypothesis will be that there is no difference between the 2 arms in primary end-point, with the p level set at p=0.05. The secondary end-points will also be compared between the 2 arms using either the Student's t test or anova test.

follicle stimulating hormone, ovarian stimulation, antimullerian hormone, antral follicle count, assisted reproductive technologies

Start dose of recombinant Follicle-Stimulating Hormone (rFSH) based on AFC guide AFC < 6 on both ovary: 375 IU FSH 6<AFC <=15 on both ovary: 225 IU FSH AFC> 15 on both ovary: 150 IU FSH

Start dose of FSH based on AMH guide AMH < 5 pmol/L or < 0.7ng/ml: 375 IU FSH AMH 5 to < 15 pmol/L or 0.7 to 2.1ng/ml: 225 IU FSH AMH ≥ 15 pmol/L or > 2.1ng/ml: 150 IU FSH

Inclusion Criteria: Starting a treatment with GONAL-f® according to the decision of the investigator and in accordance with the indication and dosing recommendation Age < 40 years at the time of GONAL-f® dosing BMI < 28 kg/m2 An early follicular phase (Day 2-4) serum levels of basal FSH ≤12 IU/L measured in the site's own laboratory and taken within 2 months prior to down-regulation start Receiving long Gonadotropin-Releasing Hormone (GnRH) agonist protocol (starting on day 21 of preceding cycle until day of hCG) Agreement to participate in the study, and to disclose any medical events to the investigator. The subject must be willing and able to comply with the protocol requirements for the duration of the study. Have given written informed consent with the understanding that the subject may withdraw consent at any time without prejudice to future medical care. Exclusion Criteria: Simultaneous participation in an interventional clinical trial. Concommitant use of either Luteinizing Hormone or human menopausal gonadotropin/urinary FSH preparations in study cycle