CONSORT Randomized Controlled Trial in Assisted Reproductive Technology

Study Overview
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Brief Summary
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The overall objective of this trial is to compare the ovarian response in assisted reproductive technology (ART) subjects administered GONAL f® according to the 'Consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment' (CONSORT) calculator versus given a standard GONAL f® dose of 150 International Unit (IU) per day.

Official Title
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A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 150 IU Per Day for Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology (ART)

Conditions
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Infertility

Intervention / Treatment
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* Drug: GONAL f® prefilled pen
* Drug: GONAL f® prefilled pen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used Between her 18th and 35th birthday (35 not included) at the time of the randomization visit Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length Have an early follicular phase (Day 2-4) serum level of basal FSH lower than or equal to 12 International Unit per Liter (IU/L) measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down-regulation start) Presence of both ovaries Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization Have at least 1 wash-out cycle (defined as greater than or equal to 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotropin releasing hormone (GnRH) agonist therapy Willing and able to comply with the protocol for the duration of the trial Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care Exclusion Criteria: Have greater than or equal to 2 previous ART cycles with a poor response to gonadotrophin stimulation (defined as lower than or equal to 5 mature follicles and/or lower than or equal to 3 oocytes collected) or have greater than or equal to 2 previous ART cycles with a hyper response (defined as greater than or equal to 25 oocytes retrieved) Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible Have previous severe ovarian hyperstimulation syndrome (OHSS) Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS Presence of endometriosis requiring treatment Uterine myoma requiring treatment Any contraindication to being pregnant and/or carrying a pregnancy to term Extra-uterine pregnancy within the last 3 months prior to screening History of 3 or more miscarriages (early or late miscarriages) due to any cause Tumors of the hypothalamus and pituitary gland Ovarian enlargement or cyst of unknown etiology Ovarian, uterine or mammary cancer A clinically significant systemic disease Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner, Abnormal gynecological bleeding of undetermined origin Known allergy or hypersensitivity to human gonadotrophin preparations, Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit Entered previously into this trial or simultaneous participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CONSORT Dosing<br>GONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator | Drug: GONAL f® prefilled pen<br>* GONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only<br>* Other names: GONAL-f® Prefilled Pen;|
| Active Comparator: Standard Dosing<br>GONAL-f® at a standard dose of 150 IU per day | Drug: GONAL f® prefilled pen<br>* GONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice.<br>* Other names: GONAL-f® Prefilled Pen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Oocytes Retrieved Per Participant | Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. | 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total GONAL-f® Dose |  | Start of treatment until end of stimulation cycle (approximately 28 days) | 
| Mean GONAL-f® Daily Dose |  | Start of treatment until end of stimulation cycle (approximately 28 days) | 
| Total Number of GONAL-f® Stimulation Treatment Days |  | Start of treatment until end of stimulation cycle (approximately 28 days) | 
| Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment | Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment. | Start of treatment until Day 15-20 post-hCG | 
| Percentage of Participants With Biochemical Pregnancies | Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy. | Start of treatment until Day 15-20 Post-hCG | 
| Number of Participants With Fetal Sacs and Fetal Hearts | Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy. | Day 35-42 Post-hCG | 
| Implantation Rate | Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. | Day 35-42 Post-hCG | 
| Number of Participants With Multiple Pregnancies | Multiple pregnancy was defined as 2 or more fetal hearts with activity. | Day 35-42 Post-hCG | 
| Serum Progesterone (P4) Levels |  | End of stimulation cycle (approximately 28 days) | 
| Percentage of Participants With Clinical Pregnancy | Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG. | Day 35-42 Post-hCG | 
| Number of Participants With OHSS | OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. | Start of treatment until Day 15-20 Post-hCG | 
| Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome | Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up). | up to 9 month (following the end of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Assisted reproductive technology