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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
136
Cetrotide® 0.25 mg will be administered subcutaneously once daily from Day 1 (Day 0 of stimulation period \[S0\]) until r-hCG day (at least 2 follicles \>=17 mm)
Cetrotide® 0.25 mg will be administered subcutaneously once daily from Day 7 (Day 6 of stimulation period \[S6\]) until r-hCG day (at least 2 follicles \>=19 mm)
The r-hCG will be administered subcutaneously as a single dose of 250 microgram (mcg) on r-hCG day
Research Site
Toulouse, France
Estradiol (E2) Levels on r-hCG Day
Time frame: r-hCG day (end of stimulation cycle [approximately 15 days])
Serum Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Levels
Time frame: Day 1
Serum Estradiol (E2) Levels
Time frame: Day 1
Serum Progesterone (P4) Levels
Time frame: Day 1
Anti Mullerian Hormone (AMH) Levels
Time frame: Day 0
Number of Follicles Greater Than or Equal (>=) to 17 mm (For Day 1 Protocol) or 19 mm (For Day 7 Protocol) on r-hCG Day
Time frame: r-hCG day (end of stimulation cycle [approximately 15 days])
Number and Quality of Oocytes Retrieved
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body. Oocytes were classified into 4 different categories based on their quality: mature, fractured, immature and inseminated oocytes.
Time frame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
Time frame: Day 1 up to r-hCG day (end of stimulation cycle [approximately 15 days])
Percentage of Fertilized Oocytes Retrieved
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an IVF procedure in which a single sperm is injected directly into an egg under a microscope.
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Recombinant human follicle stimulating hormone (r-hFSH) will be administered subcutaneously at a dose between 75 and 187.5 international unit (IU) once daily from Day 2 (Day 1 of stimulation period \[S1\]) until r-hCG day
Time frame: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Number of Embryos
Embryo is defined as the product of the zygote, two or three days after fertilization of the oocytes.
Time frame: Day 2-3 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Number of Blastocysts
Blastocyst is an embryo, five or six days after fertilization, with an inner cell mass, outer layer of trophectoderm and a fluid-filled blastocoele cavity.
Time frame: Day 5-6 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Number of Transferred Embryos
Embryo transfer is the procedure in which one or more embryos are placed in the uterus.
Time frame: Day 2-3 post Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Implantation Rate
Implantation rate per reporting group was measured as the number of gestational sacs observed, divided by the number of embryos transferred multiplied by 100.
Time frame: 5 weeks post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
Percentage of Participants With Clinical Pregnancy
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Time frame: 10 weeks post r-hCG day (end of stimulation cycle [approximately 15 days])
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. To avoid the participant/event combination double-count AEs and SAEs are reported separately.
Time frame: Day 1 up to end of study (15 days post last administration of study drug)