Clinical trial NCT00805935: Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)
Official title: A Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in Polycystic Ovarian Syndrome (PCOS) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovarian Syndrome
Infertility
Keywords: pre-menopausal women
PCOS
polycystic ovarian syndrome
infertility
IVF
in vitro fertilization
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-12-10
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, randomized, open-label exploratory study will be performed in approximately 200 polycystic ovary syndrome (PCOS) but otherwise healthy females undergoing in vitro fertilization (IVF). Each study center will follow its standard practice for in vitro fertilization (IVF) within the study parameters as noted in this protocol. The study centers will use marketed products purchased from Schraft's Pharmacy for all phases of the study (down-regulation, stimulation, ovulation induction, and luteal support). Subjects will be randomly assigned to highly purified menotropin (Menopur®) or follitropin beta (Follistim Pen®) for stimulation and progesterone vaginal insert (Endometrin®) or progesterone in oil for luteal support. Subjects will return to the study center for regular scheduled clinic visits as required per in vitro fertilization (IVF) protocol at the site and at specified times during the cycle (Stimulation Day 6, Day of human chorionic gonadotropin (hCG), and first serum pregnancy test) for estradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG) labs. All subjects will be required to complete a final study visit at completion of luteal support or negative serum pregnancy test following embryo transfer.


Eligibility criteria: Inclusion Criteria:

1. Pre-menopausal females between the ages of 18 and 42 years
2. Diagnosed with polycystic ovary syndrome (PCOS), using criteria adopted as the 2003 Rotterdam PCOS Consensus (2 out of 3, excluding other etiologies \[congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome\])

   * Oligo- or anovulation
   * Clinical and/or biochemical signs of hyperandrogenism
   * Polycystic ovaries
3. Body mass index (BMI) of 18-39
4. Early follicular phase (Day 3) follicle stimulating hormone (FSH) \< 15 IU/L and estradiol (E2) within normal limits
5. Documented history of infertility (e.g., unable to conceive for at least one year, or for 6 months for women \> 38 years of age, or bilateral tubal occlusion or absence, or male factor but excluding severe male factor requiring invasive or surgical sperm retrieval. Donor sperm may be used.)
6. Transvaginal ultrasound at screening consistent with findings adequate for assisted reproductive technology (ART) with respect to uterus and adnexa
7. Signed informed consent

Exclusion Criteria:

1. Gestational or surrogate carrier, donor oocyte
2. Presence of any clinically relevant systemic disease (e.g., uncontrolled thyroid or adrenal dysfunction, an organic intracranial lesion such as a pituitary tumor, insulin-dependent diabetes mellitus, uterine cancer)
3. Surgical or medical condition which, in the judgment of the Investigator or Sponsor, may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used
4. Two or more previous failed in vitro fertilization (IVF) cycles or in vitro fertilization (IVF)/assisted reproductive technology (ART) failure due to a poor response to gonadotropins, defined as development of 2 mature follicles
5. History of recurrent pregnancy loss, defined as more than two clinical losses
6. Presence of abnormal uterine bleeding of undetermined origin
7. Current or recent substance abuse, including alcohol or smoking \> 10 cigarettes per day
8. Refusal or inability to comply with the requirements of the Protocol for any reason, including scheduled clinic visits and laboratory tests
9. Participation in any experimental drug study within 30 days prior to Screening
10. Severe male factor requiring invasive or surgical sperm retrieval (e.g., microsurgical epididymal sperm aspiration \[MESA\], testicular sperm extraction \[TESE\])
11. Prior hypersensitivity to any of the protocol drugs

Primary outcomes:
measure: Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3
timeFrame: weeks 1-3
Secondary outcomes:
measure: Number of Follicles Observed at Day 15
timeFrame: approximately day 15
measure: Number of Oocytes Retrieved at Day 18
timeFrame: approximately day 18
measure: Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrieved
timeFrame: approximately day 19
measure: Number of Embryos Transferred at Three Stages of Development Before Implantation
timeFrame: approximately day 24
measure: Number of Embryos Frozen
timeFrame: approximately day 24
measure: Percentage of Participants With Biochemical Pregnancy at Approximately Day 38
timeFrame: approximately day 38 (Day 14 post embryo transfer)
measure: Percentage of Participants With Clinical Pregnancy at Week 7
timeFrame: approximately Day 52
measure: Percentage of Participants With Ongoing Pregnancy at Week 9
timeFrame: approximately Day 65
measure: Estradiol Levels at Day 6
timeFrame: Day 6
measure: Human Chorionic Gonadotropin (hCG) Levels at Day 6
timeFrame: Day 6
measure: Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administration
timeFrame: approximately day 16
measure: Number of Live Births Resulting From the In Vitro Fertilization Process
timeFrame: Approximately 10 months
measure: Participants With Treatment Emergent Adverse Events
timeFrame: Week 1 to week12
Other outcomes:
Locations:
city: Littleton
country: United States
facility: Conceptions Reproductive Associates of Colorado
state: Colorado
city: Clearwater
country: United States
facility: Women's Medical Research Group LLC, Florida
state: Florida
city: Chicago
country: United States
facility: Fertility Center of Illinois
state: Illinois
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Providence
country: United States
facility: Women & Infants' Hospital of RI
state: Rhode Island
city: Bedford
country: United States
facility: Center for Assisted Reproduction
state: Texas
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
citation: Beltsos AN, Sanchez MD, Doody KJ, Bush MR, Domar AD, Collins MG. Patients' administration preferences: progesterone vaginal insert (Endometrin(R)) compared to intramuscular progesterone for Luteal phase support. Reprod Health. 2014 Nov 11;11:78. doi: 10.1186/1742-4755-11-78.