Clinical trial NCT00971152: Effect of a Higher Than Maximum 450IU Gonadotropin Dose in an In-vitro Fertilization Cycle
Official title: Effect of a Higher Than Maximum 450IU Gonadotropin Dose on Patient Outcomes in an In-Vitro Fertilization Setting: a Randomized Controlled Non-infertility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Subfertility
Keywords: IVF
dose comparison of gonadotrophins
poor responder to ovarian stimulation
Lead sponsor: Clinique Ovo
Sponsor class: INDUSTRY
Collaborators: name: Ferring Pharmaceuticals
First posted: 2009-09-03
Enrollment: 366
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This goal of this study is to evaluate the outcomes from in vitro fertilization cycles where a 450 IU daily dose of gonadotropins is administered compared to those where a 600 IU daily dose is administered for women who are at risk of a poor ovarian response in order to determine if one dose or the other results in improved cycle outcomes.


Eligibility criteria: Inclusion Criteria:

* RESIDENT OF CANADA
* Premenopausal
* Age 40 years or less at the time of enrollment
* At risk of a poor ovarian response defined as: either \<5 oocytes or \<8 follicles in a previous cycle, FSH \> 10 IU/L, AMH \< 1 pg/ml , antral follicle count less or equal to 8 or previous IVF cancellation
* Primary infertility or secondary
* Not previously undertaken a cycle that was included in this study

Exclusion Criteria:

* Simultaneous participation in another clinical trial
* Body mass index (BMI) \> 38 kg/m2
* Early follicular phase (day 2-4) serum FSH level \> 20 mIU/ml
* Any contraindication to being pregnant and carrying a pregnancy to term
* Contraindication for the use of Estrace® , Suprefact®, Menopur®, Bravelle®, hCG, and luteal phase support medication
* Any ovarian or abdominal abnormality that may interfere with adequate transvaginal ultrasound evaluation
* Administration of any investigational drugs within three months prior to study enrollment
* Patient not able to communicate adequately with the investigators and to comply with the requirements of the entire study
* Positive results of screening of either partner for HIV antibodies, Hepatitis B (other than for surface antibodies present after vaccination) or Hepatitis C
* Unwillingness to give written informed consent

Primary outcomes:
measure: Number of metaphase II oocytes retrieved during the course of one treatment cycle
timeFrame: 2 years
Secondary outcomes:
measure: Number of follicles recruited per patient during stimulation
timeFrame: 2 years
measure: Fertilization rate per patient (number of normally fertilized (with 2 pronuclei) oocytes/number of mature oocytes collected)
timeFrame: 2 years
measure: Embryo cleavage rate per patient (number of divided normally fertilized oocytes/number of normally fertilized oocytes)
timeFrame: 2 years
measure: Number of embryos available per patient
timeFrame: 2 years
measure: Number of supernumerary embryos available for cryopreservation per patient
timeFrame: 2 years
measure: Implantation rate
timeFrame: 2 years
measure: Biochemical pregnancy rate
timeFrame: 2 years
measure: Clinical pregnancy rate
timeFrame: 2 years
measure: Rate of multiple gestation
timeFrame: 2 years
measure: Ongoing pregnancy rate
timeFrame: 2 years
measure: Live birth rate
timeFrame: 2 years
measure: rate of occurrence of ovarian hyperstimulation syndrome (OHSS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Ovo Fertilité
state: Quebec
Study officials:
affiliation: ovo fertilité
name: Louise Lapensee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OVO Fertilité and OVO R & D
name: Jacques Kadoch, MD
role: STUDY_DIRECTOR
References:
citation: Srouji SS, Missmer SA, Ginsburg ES (2004) Impact of increasing gonadotropins > 450 IU on cycle outcome. Brigham and Women's Hospital, Boston, MA. Fertil Steril 82 (Suppl 2): P292.
citation: Flisser E, Krey LC, Berkeley AS (2005) Diminishing Returns of Increasing Gonadotropin Dosage in Subsequent In Vitro Fertilization (IVF) Cycles?. Fertil Steril 84 (Suppl 1) P483.
citation: Lefebvre J, Antaki R, Kadoch IJ, Dean NL, Sylvestre C, Bissonnette F, Benoit J, Menard S, Lapensee L. 450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial. Fertil Steril. 2015 Dec;104(6):1419-25. doi: 10.1016/j.fertnstert.2015.08.014. Epub 2015 Sep 8.