Clinical trial NCT00249834: Safety and Efficacy of Pre-defined, Fixed Dose of Gonal-f Pen Based on Subject Baseline Characteristics in Subjects Undergoing in Vitro Fertilization (IVF)
Official title: A Phase IIIB/IV, Open Label Study to Assess the Efficacy and Safety of a Pre-defined, Fixed Dose of Gonal-f® (Filled-by-Mass in a Prefilled Pen) Based on Subject Baseline Characteristics, for Ovarian Stimulation in Subjects Undergoing in Vitro Fertilization (IVF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: Assisted Reproductive Technology (ART)
Infertility
Ovarian stimulation
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2005-11-07
Enrollment: 166
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clinical validation of the assisted reproductive technology (ART) treatment guidelines, which determine the optimal dose of recombinant human follicle stimulating hormone (r-hFSH) based on subject baseline characteristics/predictors of ovarian response.


Eligibility criteria: Inclusion Criteria

* Be an infertile subject justifying an in-vitro fertilization/embryo transfer (IVF/ET) treatment.
* Have a male partner with semen analysis within the past six months prior to study entry 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.
* Be between her 18th and 35th birthday (35 not included).
* Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length.
* Have early follicular phase (Day 2-4) serum levels within the last 3 months prior to study entry of:
* Follicle stimulating hormone (FSH) greater than or equal to (\>=) 12 International units per liter (IU/L), and
* Oestradiol (E2) within center's local normal laboratory range values.
* Presence of both ovaries.
* Have a uterine cavity without abnormalities, which, in the investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed within the last 3 years using ultrasound (US), hysteroscopy (HSC), or hysterosalpingography (HSG).
* Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to study entry.
* Have at least one wash-out cycle (defined as \>= 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 gonadotrophin releasing hormone (GnRH) agonist therapy.
* Have a negative pregnancy test prior to beginning GnRH agonist therapy.
* Be willing and able to comply with the protocol for the duration of the study. Have given written informed consent, prior to any study-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:

* Had 2 previous ART cycles with a poor response to gonadotrophin stimulation, defined as less than or equal to (\<=) 5 mature follicles and/or \<=3 oocytes collected in any previous IVF cycle or hyper response, defined as \>=25 oocytes retrieved.
* Any medical condition, which in the judgement 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 Serono's Therapeutic Director.
* Had previous severe ovarian hyperstimulation syndrome (OHSS).
* A body mass index (BMI) greater than (\>) 30 kilogram per square meter (kg/m\^2)
* Any contraindication to being pregnant and/or carrying a pregnancy to term.
* Extra-uterine pregnancy within the last 3 months.
* History of 3 or more miscarriages (early or late miscarriages) due to any cause.
* Tumours of the hypothalamus and pituitary gland.
* Ovarian enlargement or cyst of unknown aetiology.
* Ovarian, uterine or mammary cancer.
* A clinically significant systemic disease.
* Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus.
* Abnormal gynaecological 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.
* Entered previously into this study or simultaneous participation in another clinical trial

Primary outcomes:
measure: Number of Oocytes Retrieved
timeFrame: Ovum pick up day (34 to 38 hours post r-hCG administration)
Secondary outcomes:
measure: Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
timeFrame: up to end of stimulation cycle (approximately 31 days)
measure: Mean Number of Ovarian Stimulation Days
timeFrame: up to end of stimulation cycle (approximately 31 days)
measure: Percentage of Cycles Cancelled Due to Excessive or Inadequate Response to r-hFSH
timeFrame: up to end of stimulation cycle (approximately 31 days)
measure: Number of Subjects Needing Dose Adjustment
timeFrame: 6 days post r-hFSH treatment
measure: Mean Daily Recombinant Human Follicle Stimulating Hormone (r-hFSH) Dose
timeFrame: up to end of stimulation cycle (approximately 31 days)
measure: Embryo Implantation Rate
timeFrame: 35-42 days post r-hCG administration
measure: Overall Pregnancy Rate, Clinical Rate and Multiple Pregnancy Rate
timeFrame: 35-42 days post r-hCG administration
Other outcomes:
Locations:
city: Paris
country: France
facility: Medical Information
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Olivennes F, Howles CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V; CONSORT study group. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2009 Feb;18(2):195-204. doi: 10.1016/s1472-6483(10)60256-8.
citation: Olivennes F, Howies CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2011 Feb;22 Suppl 1:S73-82. doi: 10.1016/S1472-6483(11)60012-6.