Analysis of Two Therapeutic With Cetrotide® in Polycystic Ovarian (PCO) Women in Assisted Reproductive Technology (ART)

A Phase IIIb Randomized Open-label Study to Compare the Estradiol Level on the Releasing Day in Two Regimen of Cetrotide® 0.25 mg Used From Day 1 or From Day 7 of the Menstrual Cycle (Day 0 or Day 6 of Stimulation) in Polycystic Ovarian (PCO) Women in ART (IVF/ICSI).

This is a randomized open-label study to compare between in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes of the two regimen of Cetrotide® (Cetrorelix acetate) which are 0.25 milligram (mg) used from Day 1 or Day 7 of the menstrual cycle (Day 0 or Day 6 of stimulation) in polycystic ovarian (PCO) women in assisted reproductive technology (ART).

Polycystic ovarian syndrome population is an androgenic syndrome characterized by a wide spectrum of clinical manifestations such as obesity, hirsutism, insulin resistance, diabetes and presence of specific ultrasonic features.

Cetrotide®, cetrorelix acetate, is an antagonist of luteinizing-hormone-releasing hormone (LHRH). Cetrotide® is registered in 70 countries (including France) for the prevention of premature ovulation in subjects undergoing a controlled ovarian stimulation, followed by oocyte pick-up and ARTs. Ovitrelle®, active ingredient human chorionic-gonadotropin alfa, is administered to trigger final follicular maturation and luteinization after stimulation of follicular growth.

OBJECTIVES

Primary objective:

• To compare the hormonal level of plasmatic estradiol on the releasing day (day of r-hCG administration) induced by Cetrotide® 0.25 mg/day started on Day 1 (Group A: Day 1) or on Day 7 (Group B: Day 7) of the menstrual cycle (Day 0 (S0) or Day 6 (S6) of stimulation) in PCO subjects undergoing IVF/ICSI procedures.

Secondary objectives:

• To compare the hormonal changes during the stimulation induced by Cetrotide® in A and B Groups
• To assess by ultrasound scans (US) the follicular development induced by Cetrotide® in A and B Groups
• To assess biological and clinical outcomes induced by Cetrotide® in A and B Groups
• To monitor safety of Cetrotide in A and B Groups

The trial will be conducted on an outpatient basis. Once each subject has met all eligibility criteria, they will be randomly assigned in one of the two treatment groups.

Inclusion Criteria:

• Female subjects with PCO or Polycystic ovary syndrome (PCOS) according to the revised 2003 Rotterdam Consensus
• Female subjects suitable for IVF/ICSI, undergoing first or second attempt
• 18-35 years old, Body Mass Index (BMI) less than or equal to 32, non-smoking at least from Visit 0 (V0)
• Normal FSH value (less than 10 international unit per liter [IU/L]) on Day 3 of spontaneous cycle within 12 months prior to the trial
• Anti Mullerian Hormone (AMH) value (greater than 1.5 nanogram per milliliter [ng/mL]) of a spontaneous cycle within 12 months prior to the trial or at least at V0
• No history of active genito-urinary infection
• Normal thyroid function (or adequate substitution for at least 3 months)
• Negative cervical papanicolaou test within the last 12 months prior to study entry
• No gonadotropins, for at least one month prior to the trial
• No metformin therapy for at least one month prior to Visit 1 (V1)
• Subject who is able to participate in the trial and has provided written, informed consent.

Exclusion Criteria:

• Ongoing pregnancy, any pregnancy within 3 months prior to study entry, or any contraindication to pregnancy or carrying pregnancy to term
• Drilling 3 months prior to V0
• Uterine malformation, diethylstilbestrol syndrome, synechia
• Female subjects with World Health Organization (WHO) Type I or III anovulation
• Female subjects with hyperprolactinemia
• Female subjects with more than 2 recurrent miscarriages (early or late, and for any reasons)
• Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus, for subject or partner
• Abnormal gynecological bleeding of undetermined origin
• History of major thromboembolic disease
• Endometriosis (Grade III or IV)
• Presence or history of malignant tumors and related treatment
• Known case of tumors of the hypothalamus or pituitary gland
• Clinically significant systemic disease or clinically significant abnormal hematology, chemistry, or urinalysis results at screening
• Known allergic reaction or hypersensitivity to Cetrotide® or Ovitrelle®
• Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
• Participation in another clinical trial within 3 months prior to study entry.