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

Study Overview
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Brief Summary
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Prospective open label, randomised, parallel group, comparative pilot.

Detailed Description
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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.

Official Title
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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

Conditions
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Infertility

Intervention / Treatment
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* Drug: Menotrophin
* Drug: Follitropin alfa


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menotrophin<br> | Drug: Menotrophin<br>* 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.<br>* Other names: highly purified menotrophin;|
| Active Comparator: Follitropin alfa<br> | Drug: Follitropin alfa<br>* 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.<br>* Other names: recombinant FSH;|

What is the study measuring?
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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 |