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Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS)

Registration Number
NCT00805935
Lead Sponsor
Ferring Pharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
110
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Follitropin beta/Progesterone in oilProgesterone in oilFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone vaginal insertProgesterone vaginal insertHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone vaginal insertleuprolide acetateHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone in oilProgesterone in oilMenotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone in oilleuprolide acetateMenotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follitropin beta/Progesterone vaginal insertProgesterone vaginal insertFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follitropin beta/Progesterone vaginal insertleuprolide acetateFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follitropin beta/Progesterone in oilleuprolide acetateFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone vaginal insertMenotropinHighly purified menotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 100 mg starts on the day following oocyte retrieval and continues for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Menotropin/Progesterone in oilMenotropinMenotropin (Menopur®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follitropin beta/Progesterone vaginal insertFollitropin betaFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone vaginal insert (Endometrin®) 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Follitropin beta/Progesterone in oilFollitropin betaFollitropin beta (Follistim Pen®) 225 IU from day 1-6 of menstrual cycle. May be adjusted up to 450 IU daily for more days until human chorionic gonadotropin (hCG) criteria are met. Progesterone in oil 50 mg injections start on the day following oocyte retrieval and continue for a total duration of 10 weeks or until a negative pregnancy test is obtained.
Primary Outcome Measures
NameTimeMethod
Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3weeks 1-3

A count of participants whose discontinuation was clearly documented on the study completion/termination form as cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS).

Secondary Outcome Measures
NameTimeMethod
Number of Follicles Observed at Day 15approximately day 15

The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase.

Number of Oocytes Retrieved at Day 18approximately day 18

The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures.

Percentage of Oocytes Fertilized of the Total Number of Oocytes Retrievedapproximately day 19

The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved.

Number of Embryos Transferred at Three Stages of Development Before Implantationapproximately day 24

The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells.

Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape.

Number of Embryos Frozenapproximately day 24

The number of embryos that were not transferred but instead were frozen for future use.

Percentage of Participants With Biochemical Pregnancy at Approximately Day 38approximately day 38 (Day 14 post embryo transfer)

Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer.

Percentage of Participants With Clinical Pregnancy at Week 7approximately Day 52

Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.

Percentage of Participants With Ongoing Pregnancy at Week 9approximately Day 65

Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination.

Estradiol Levels at Day 6Day 6

Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels.

Human Chorionic Gonadotropin (hCG) Levels at Day 6Day 6

Blood tests were sent to a central laboratory to obtain hCG levels.

Progesterone Levels at Human Chorionic Gonadotropin (hCG) Administrationapproximately day 16

Blood tests were sent to a central laboratory to obtain progesterone levels.

Number of Live Births Resulting From the In Vitro Fertilization ProcessApproximately 10 months

Number of live births resulting from the IVF process

Participants With Treatment Emergent Adverse EventsWeek 1 to week12

Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale:

mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable.

Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly.

Trial Locations

Locations (6)

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Women & Infants' Hospital of RI

🇺🇸

Providence, Rhode Island, United States

Conceptions Reproductive Associates of Colorado

🇺🇸

Littleton, Colorado, United States

Center for Assisted Reproduction

🇺🇸

Bedford, Texas, United States

Women's Medical Research Group LLC, Florida

🇺🇸

Clearwater, Florida, United States

Fertility Center of Illinois

🇺🇸

Chicago, Illinois, United States

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