Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF) (PREDICT)

This study has been completed.
Sponsor:
Collaborator:
Ferring Arzneimittel GmbH
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01225835
First received: October 7, 2010
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels might be a useful predictor for the success rate of the ongoing pregnancy rates


Condition Intervention Phase
Infertility
Drug: Menotrophin
Drug: Follitrophin alpha
Drug: Cetrorelix
Drug: Choriongonadotropin
Drug: Progesterone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Highly Purified Menotrophin and Recombinant Follicle Stimulating (rFSH, Follitrophin Alpha) in Subfertile Female Patients Undergoing IVF on Progesterone Serum Levels During the Follicular Phase and Their Possible Use as Predictors for the Success Rate of Ongoing Pregnancies

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration [ Time Frame: approximately day 10 ] [ Designated as safety issue: No ]
    Ovulation induction was performed by administration of hCG once three follicles >=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (<39 years and >=39 years).


Secondary Outcome Measures:
  • Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration [ Time Frame: Day 7, approximately Day 10 (hCG Administration) ] [ Designated as safety issue: No ]
    The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.

  • Percentage of Participants With Ongoing Pregnancy [ Time Frame: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test) ] [ Designated as safety issue: No ]
    Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.

  • Number of Follicles at hCG Administration [ Time Frame: approximately day 10 ] [ Designated as safety issue: No ]
    Number of follicles >=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.

  • Average Follicle Diameter at hCG Administration [ Time Frame: approximately day 10 ] [ Designated as safety issue: No ]
  • Number of Cumulus-oocyte Complexes Retrieved [ Time Frame: approximately day 12 after study start ] [ Designated as safety issue: No ]
    Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.

  • Number of Pronuclear Oocytes [ Time Frame: approximately day 13 after study start ] [ Designated as safety issue: No ]
    Pronuclear oocytes are fertilized oocytes.

  • Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade [ Time Frame: approximately day 13 ] [ Designated as safety issue: No ]

    The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality.

    Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once.


  • Number of Embryos Transferred [ Time Frame: approximately day 14 ] [ Designated as safety issue: No ]
    Mean number of embryos transferred 2-3 days following oocyte retrieval.

  • Best Quality of an Embryo Transferred [ Time Frame: approximately day 14 ] [ Designated as safety issue: No ]

    Embryo quality was measured by the following grades:

    • Grade 1: Evenly sized cells, regular cleavage, no fragmentation
    • Grade 2: Regular or slightly irregular cleavage, <=20% fragmentation
    • Grade 2.5: Regular or slightly irregular cleavage, >20%and <=50% fragmentation
    • Grade 3: Irregular cleavage, >50% fragmentation, >1 intact cell
    • Grade 4: Extensive fragmentation, only 1 cell intact
    • Grade 5: Totally fragmented, no viable cells.

    Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.


  • Number of Frozen Oocytes at Pronuclear Stage [ Time Frame: approximately day 14 ] [ Designated as safety issue: No ]
    No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.

  • Endometrial Thickness on Day of hCG Administration [ Time Frame: approximately day 10 ] [ Designated as safety issue: Yes ]
    Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.

  • Estradiol (E2) Levels on Day of hCG Administration [ Time Frame: approximately day 10 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Successful Embryo Transfer [ Time Frame: approximately day 18 ] [ Designated as safety issue: No ]
  • Number of Days Stimulated With Gonadotrophins [ Time Frame: Day 1 up to Day 12 ] [ Designated as safety issue: No ]
    Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.

  • Number of Ampoules of Gonadotrophins Used [ Time Frame: Day 1 up to Day 12 ] [ Designated as safety issue: No ]
    Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.

  • Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test [ Time Frame: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test ] [ Designated as safety issue: No ]
    A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.

  • Summary of Pregnancy Outcome [ Time Frame: up to 10 months ] [ Designated as safety issue: No ]
    Pregnancy outcomes were reported at the optional long-term follow up visit.


Enrollment: 124
Study Start Date: October 2010
Study Completion Date: June 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Menotrophin
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Drug: Menotrophin
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
Other Name: Menogon® HP
Drug: Cetrorelix
Participants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction.
Other Names:
  • Cetrotide®
  • GnRH antagonist
Drug: Choriongonadotropin
10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles >+17 mm diameter as shown by pelvic ultrasound examination.
Other Names:
  • Brevactid®
  • human chorionic gonadotropin (hCG)
Drug: Progesterone
Vaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14).
Other Names:
  • Crinone®
  • intravaginal progesterone
Active Comparator: Follitrophin Alpha
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Drug: Follitrophin alpha
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
Other Name: Gonal-f®
Drug: Cetrorelix
Participants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction.
Other Names:
  • Cetrotide®
  • GnRH antagonist
Drug: Choriongonadotropin
10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles >+17 mm diameter as shown by pelvic ultrasound examination.
Other Names:
  • Brevactid®
  • human chorionic gonadotropin (hCG)
Drug: Progesterone
Vaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14).
Other Names:
  • Crinone®
  • intravaginal progesterone

  Eligibility

Ages Eligible for Study:   34 Years to 42 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Subfertile premenopausal female patients eligible for in vitro fertilisation (IVF) treatment
  • Aged ≥34 and ≤42 years
  • Body mass index of >18 and <28 kg/m^2
  • Normal pelvic ultrasound at Screening
  • No more than two previous gonadotrophin stimulated cycles of IVF or intracytoplasmic sperm injection (ICSI) in the history of infertility treatment (gonadotrophin stimulated cycles not used for IVF or ICSI do not count; Clomifen cycles are no exclusion criterion)
  • At least 3 consecutive ovulatory menstrual cycles of 24-35 days
  • No fertility stimulating drugs at all
  • Sperm of partner classified as normal according to World Health Organisation (WHO) 2010 criteria
  • Clinically normal baseline haematology, clinical chemistry, and urinalysis values
  • Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within the last 6 months prior to Screening
  • Endocrine test results within the clinically normal limits at Screening

Exclusion Criteria:

  • Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus)
  • A history of or current endocrine disease (excluding treated hypothyreosis), including polycystic ovary syndrome (PCOS) and hyperprolactinaemia
  • A history of coagulation disorders
  • Persistent ovarian cysts (>3 months)
  • A history of hypersensitivity to any of the constituents of the study medication or related compounds
  • Diagnosed poor (<3 oocytes) responders to prior gonadotrophin stimulated ART-cycle
  • History of severe ovarian hyperstimulation syndrome in former gonadotrophin stimulated assisted reproductive technology (ART)-cycle
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225835

Locations
Germany
Fertility Center Berlin
Berlin, Germany
Praxisklinik Sydow am Gendarmenmarkt
Berlin, Germany
Kinderwunschzentrum Dortmund
Dortmund, Germany
Universitätsklinikum Duesseldorf, Frauenklinik
Dusseldorf, Germany
Praxis für Kinderwunschbehandlung
Erlangen, Germany
NOVUM Zentrum
Essen, Germany
IVF Zentrum
Saar, Germany
Endokrinologikum Ulm
Ulm, Germany
Sponsors and Collaborators
Ferring Pharmaceuticals
Ferring Arzneimittel GmbH
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

No publications provided

Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01225835     History of Changes
Other Study ID Numbers: FE999906 CS11, 2010-019411-37
Study First Received: October 7, 2010
Results First Received: December 19, 2013
Last Updated: February 17, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Infertility
Genital Diseases, Female
Genital Diseases, Male
Cetrorelix
Chorionic Gonadotropin
Progesterone
Fertility Agents
Fertility Agents, Female
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014