Clinical trial NCT00829244: CONSORT Randomized Controlled Trial in Assisted Reproductive Technology
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: Infertility
Assisted reproductive technology
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-01-26
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment
2. 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
3. Between her 18th and 35th birthday (35 not included) at the time of the randomization visit
4. Body mass index (BMI) lower than 30 kilogram per square meter (kg/m\^2) where the BMI is calculated according to the formula
5. Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
6. 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)
7. Presence of both ovaries
8. Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy
9. Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization
10. 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
11. Willing and able to comply with the protocol for the duration of the trial
12. 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:

1. 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)
2. 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
3. Have previous severe ovarian hyperstimulation syndrome (OHSS)
4. Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
5. Presence of endometriosis requiring treatment
6. Uterine myoma requiring treatment
7. Any contraindication to being pregnant and/or carrying a pregnancy to term
8. Extra-uterine pregnancy within the last 3 months prior to screening
9. History of 3 or more miscarriages (early or late miscarriages) due to any cause
10. Tumors of the hypothalamus and pituitary gland
11. Ovarian enlargement or cyst of unknown etiology
12. Ovarian, uterine or mammary cancer
13. A clinically significant systemic disease
14. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner,
15. Abnormal gynecological bleeding of undetermined origin
16. Known allergy or hypersensitivity to human gonadotrophin preparations,
17. Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit
18. Entered previously into this trial or simultaneous participation in another clinical trial

Primary outcomes:
measure: Number of Oocytes Retrieved Per Participant
timeFrame: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)
Secondary outcomes:
measure: Total GONAL-f® Dose
timeFrame: Start of treatment until end of stimulation cycle (approximately 28 days)
measure: Mean GONAL-f® Daily Dose
timeFrame: Start of treatment until end of stimulation cycle (approximately 28 days)
measure: Total Number of GONAL-f® Stimulation Treatment Days
timeFrame: Start of treatment until end of stimulation cycle (approximately 28 days)
measure: Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment
timeFrame: Start of treatment until Day 15-20 post-hCG
measure: Percentage of Participants With Biochemical Pregnancies
timeFrame: Start of treatment until Day 15-20 Post-hCG
measure: Number of Participants With Fetal Sacs and Fetal Hearts
timeFrame: Day 35-42 Post-hCG
measure: Implantation Rate
timeFrame: Day 35-42 Post-hCG
measure: Number of Participants With Multiple Pregnancies
timeFrame: Day 35-42 Post-hCG
measure: Serum Progesterone (P4) Levels
timeFrame: End of stimulation cycle (approximately 28 days)
measure: Percentage of Participants With Clinical Pregnancy
timeFrame: Day 35-42 Post-hCG
measure: Number of Participants With OHSS
timeFrame: Start of treatment until Day 15-20 Post-hCG
measure: Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome
timeFrame: up to 9 month (following the end of treatment)
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Research Site
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Pablo Arriagada, MD
role: STUDY_DIRECTOR
References:
citation: Olivennes F, Trew G, Borini A, Broekmans F, Arriagada P, Warne DW, Howles CM. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa. Reprod Biomed Online. 2015 Mar;30(3):248-57. doi: 10.1016/j.rbmo.2014.11.013. Epub 2014 Dec 15.