A Study of the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant Follitropin Alfa

A Prospective, Open Label, Randomised, Parallel Group, Comparative Pilot Study to Study the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant FSH (Follitropin Alfa) Administered Subcutaneously to Subfertile Female Patients Undergoing IVF Using Antagonist Downregulation

Prospective open label, randomised, parallel group, comparative pilot.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Menotrophin; Drug: Follitropin alfa

Detailed Description

Ongoing pregnancy rate, defined as positive fetal heart action 9 weeks after the first positive pregnancy test. Number/diameter of follicles, number of oocytes retrieved, number of pronuclear oocytes (referred to as zygotes or pre-embryos in the UK), quality of pronuclear stage oocytes, number of embryos transferred, quality of embryos, number of frozen embryos, endometrial thickness and morphology on day of HCG administration, estradiol levels at day of HCG administration, implantation rate, number of days stimulated with gonadotrophins and number of ampoules used, clinical pregnancy rate at 6 weeks after the first positive pregnancy test, pregnancy outcome.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Dortmund, Germany, 44135
    • Gemeinschaftspraxis und Tagesklinik, Olpe 19
  • Heidelberg, Germany, 69115
    • Universitats-Frauenklinik Heidelberg Abt. Gynakologische Endokrinologie und Fertilitatsstorungen, Voßstr. 9
  • Hildesheim, Germany, 1134
    • Gemeinschaftspraxis und Tagesklinik, Zingel 29
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh, 51 Little France
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary, Great George Street
  • Sheffield, United Kingdom, S10 2SF
    • The Royal Hallamshire Hospital, University of Sheffield, Jessop Wing, Tree Root Walk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Female patients aged > or = 20 and < or = 35 years with a BMI of >18 and <32 kg/m2 who have received no more than two previous cycles of in vitro fertilisation (IVF) or other assisted reproductive technique (ART) and whose partners have normal sperm (according to WHO 1999 criteria).

Inclusion criteria:

• Signed informed consent;
• Subfertile premenopausal female patients eligible for IVF treatment;
• Aged >=20 and <=35 years;
• Body mass index of >18 and <32 kg/m2
• Normal endocrine assessment within the last 6 months;
• Normal pelvic ultrasound (showing two ovaries, no ovarian abnormalities and normal uterus) within the last 6 months;
• Receipt of no more than two previous cycles of IVF (or other ART);
• At least 3 consecutive ovulatory menstrual cycles of 24-35 days, and documented evidence of ovulatory cycles within the previous 12 months;
• No fertility-modifying treatment within the 3 months prior to this treatment cycle;
• Infertility attributable to or in association with either tubal factor, or unexplained causes;
• Sperm of partner classed as normal according to WHO 1999 criteria within the year prior to beginning therapy;
• Negative serum beta-HCG pregnancy test prior to beginning therapy;
• Clinically normal baseline haematology, clinical chemistry, and urinalysis parameter values, negative serum HBsAg and HIV antibody tests;
• Screening endocrine test results (estradiol, LH, FSH, progesterone, prolactin, TSH) in early follicular phase within the normal limits for the clinical laboratory.

Exclusion criteria

• Presence of any clinically relevant systemic disease(e.g. insulin- dependent diabetes mellitus);
• A history of or current endocrine disease, including polycystic ovary- like syndrome and hyperprolactinaemia;
• A history of coagulation disorders;
• Persistent ovarian cysts;
• Contraindications for the use of gonadotrophins or GnRH antagonists;
• A history of hypersensitivity to any of the constituents of the study medication or related compounds;
• Three or more previous cycles of IVF (or other ART);
• A history of alcohol abuse (more than 30 units per week on a regular basis);
• History of chemo- or radiotherapy;
• Currently breast-feeding, pregnant or with a contraindication to pregnancy;
• Diagnosed poor responders in prior IVF treatment;
• History of severe ovarian hyperstimulation syndrome (OHSS) (4 or 5) in former IVF treatment;
• Investigational drug within the 30 days prior to treatment;
• Any other condition or history that the investigator considers might increase the risk to the individual.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menotrophin	Drug: Menotrophin; 150 IU Menotrophin daily subcutaneous injection for a maximum of 13 days. In the event of hyperstimulation, the dose was reduced to 75 IU daily.; Other Names: Menopur; hMG; highly purified menotrophin
Active Comparator: Follitropin alfa	Drug: Follitropin alfa; 150 IU follitropin alfa daily by subcutaneous injection for a maximum of 13 days. In the event of hyperstimulation, the dose was reduced to 75 IU daily.; Other Names: recombinant FSH; rFSH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an Ongoing Pregnancy	Number of participants who met human chorionic gonadotrophin (hCG) criterion, received an embryo transfer, tested positive with a serum pregnancy test 11-14 days after embryo transfer and had an ongoing pregnancy (defined as positive fetal heart action) at ≥ 9 weeks after the first positive pregnancy test.	Approx week 13; 9 weeks or more after the 1st positive pregnancy test
Percentage of Participants With an Ongoing Pregnancy	Percentage of participants who had an ongoing pregnancy ≥ 9 weeks after the first positive pregnancy test, as indicated by positive fetal heart action.	Approx week 13; 9 weeks or more after the first positive pregnancy test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Varying Numbers of Follicles That Were Greater Than or Equal to 17 Millimeters	The criterion for ovulation induction was three follicles ≥ 17 mm diameter as shown by pelvic ultrasound examination. Patients were assessed by pelvic ultrasound on the morning (prior to menotrophin or follitropin alfa administration) of Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13) until the criterion was met.	Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13)
Participants With Varying Numbers of Oocytes Retrieved	Number of participants with grouped by the number of oocytes retrieved. Oocytes were retrieved following ovulation induction by subcutaneous administration of human chorionic gonadotrophin (hCG) in the form of choriogonadotropin alfa at a dose of 250 micrograms once participants reached the criteria of at least three follicles with >= 17mm in diameter.	Approximately study day 15
Participants With Varying Numbers of Pronuclear Stage Oocytes	Number of participants with various groupings of pronuclear oocytes retrieved 16-20 hours after insemination.	Approximately study day 15
Participants With Varying Numbers of Embryos Transferred	Number of participants with various categories of numbers of embryos transferred.	Approximately study day 17
Participants With Varying Numbers of Embryos Frozen	Number of participants with different categories of number of embryos frozen.	Approximately study day 17
Mean Number of Days Stimulated With Gonadotrophins	Number of days stimulated with study drug until participant met the criteria for ovulation induction. Ovulation induction criteria is three follicles greater than or equal to 17 mm diameter as shown by pelvic ultrasound examination.	study days 1 - 13
Pregnancy Outcomes	Long term follow-up to determine the outcome of the pregnancy.	Approximately 10 months
Mean Endometrial Thickness	Measurement performed on day of human chorionic gonadotrophin (hCG) administration/ovulation induction.	Day 7 or 9 or 11 or 13
Mean Estradiol Level	Measurement on day of human chorionic gonadotrophin (hCG) administration / ovulation induction.	Day 7 or 9 or 11 or 13

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimate): November 23, 2005

Study Record Updates

• Last Update Posted (Estimate): February 26, 2010
• Last Update Submitted That Met QC Criteria: February 12, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Follicle Stimulating Hormone; Menotropins
• Other Study ID Numbers: FE999906 CS004 (PROSPECT); 2004-001307-35 (Registry Identifier: EudraCT)