Efficacy of a Pharmacogenetic Controlled Ovarian Stimulation Protocol Based on Follicle Stimulating Hormone Receptor (FSHR) Genotype Status

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2008 by Medical University of Vienna.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00749853
First received: September 8, 2008
Last updated: NA
Last verified: September 2008
History: No changes posted
  Purpose

Available data from in vitro studies and clinical trials indicate that genetic factors play a significant role in the success of controlled ovarian stimulation (COS) prior to in vitro fertilization - embryo trandfer (IVF-ET). Women with the FSHR Ser680Asn Ser/Ser genotype make up between 13% and 26% of women undergoing IVF-ET and are characterised by higher basal FSH serum concentrations, the need for a higher amount of FSH for COS, and a higher risk of poor response to COS and cycle cancellation.

The investigators therefore intend to perform a study to investigate whether a dose-intensified COS protocol based on FSHR genotype status in women with the FSHR Ser680Asn Ser/Ser genotype is more effective than routine management in terms of

  • the mean number of follicles
  • the mean number of embryos
  • the rate of poor responders
  • the rate of women with cycle cancellations, and v) the clinical pregnancy rates.

Eligible women will be randomized to a stimulation protocol characterised by a longer duration and increased dosage of FSH stimulation (group A) or a standard stimulation protocol (group B).


Condition Intervention Phase
Sterility
Drug: follicle stimulating hormone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Randomized Open Trial to Evaluate the Efficacy of an Ovarian Stimulation Protocol Based on FSH Receptor Genotype

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • clinical pregnancy rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • follicle count, cycle cancellation rate, poor responder rate [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: January 2009
Estimated Study Completion Date: November 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Pituitary down-regulation will be achieved using buserelin (Suprefact®, Hoechst, Frankfurt, Germany) at a fixed daily dose of 200 mg s.c., according to a long agonist protocol, starting on day 2 of the normal menstrual cycle. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The initial r-hFSH dose will be 250 IU s.c. daily for 5 days, after which the dose will be increased to a maximum of 450 IU per day using a step-up protocol with steps of 50 IU/day.
Drug: follicle stimulating hormone
Pituitary down-regulation will be achieved using buserelin (Suprefact®, Hoechst, Frankfurt, Germany) at a fixed daily dose of 200 mg s.c., according to a long agonist protocol, starting on day 2 of the normal menstrual cycle. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The initial r-hFSH dose will be 250 IU s.c. daily for 5 days, after which the dose will be increased to a maximum of 450 IU per day using a step-up protocol with steps of 50 IU/day.
Other Name: buserelin, r-hFSH, r-hLH
Active Comparator: 2
No pituitary down-regulation will be performed. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The r-hFSH dose will be 150 IU s.c. daily for 11 consecutive days.
Drug: follicle stimulating hormone
No pituitary down-regulation will be performed. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The r-hFSH dose will be 150 IU s.c. daily for 11 consecutive days.
Other Name: buserelin, r-hFSH, HCG

Detailed Description:

Women in group A will undergo controlled ovarian stimulation according to the following protocol:

Pituitary down-regulation will be achieved using buserelin (Suprefact®, Hoechst, Frankfurt, Germany) at a fixed daily dose of 200 mg s.c., according to a long agonist protocol, starting on day 2 of the normal menstrual cycle. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The initial r-hFSH dose will be 250 IU s.c. daily for 5 days, after which the dose will be increased to a maximum of 450 IU per day using a step-up protocol with steps of 50 IU/day.

Once the leading follicle has reached a diameter of 14 mm, patients will receive r-hLH (lutropin alfa; Luveris®, Serono Austria GmbH, Vienna, Austria) at a dose of 75 IU s.c. for a maximum of 10 days. A dose of 75 IU LH per day was chosen based on findings from a controlled, prospective, dose-finding study in gonadotrophin-deficient women (WHO I classification) (7). Ovulation will be induced by administration of HCG (Profasi®, Serono Austria GmbH, Vienna, Austria), 10 000 IU i.m. or s.c., when at least two follicles have reached a diameter of >17 mm.

Oocyte retrieval will be performed by ultrasound-guided follicular aspiration techniques 34-38 h after administration of HCG. IVF will be performed according to standard practices at our institution. A maximum of three embryos will be transferred 48 h after oocyte retrieval (ESHRE Committee on Good Clinical and Laboratory Practice, 1995 ). Patients will receive micronized progesterone, 600 mg/day, by vaginal administration for at least the first 3 weeks of pregnancy, beginning on the day of embryo transfer.

Women in group B will undergo ovarian hyperstimulation according to the following protocol:

No pituitary down-regulation will be performed. Treatment with r-hFSH (Gonal-F®, Serono Austria GmbH, Vienna, Austria) will be started in women with serum E2 concentrations <200 pmol/l and no follicles >15 mm in diameter or ovarian cysts on ultrasonographic examination. The r-hFSH dose will be 150 IU s.c. daily for 11 consecutive days.

Once the leading follicle has reached a diameter of 14 mm, patients will receive r-hLH (lutropin alfa; Luveris®, Serono Austria GmbH, Vienna, Austria) at a dose of 75 IU s.c. for a maximum of 10 days. A dose of 75 IU LH per day was chosen based on findings from a controlled, prospective, dose-finding study in gonadotrophin-deficient women (WHO I classification) (European Recombinant Human LH Study Group, 1998 ). Ovulation will be induced by administration of HCG (Profasi®, Serono Austria GmbH, Vienna, Austria), 10 000 IU i.m. or s.c., when at least two follicles have reached a diameter of >17 mm.

Oocyte retrieval will be performed by ultrasound-guided follicular aspiration techniques 34-38 h after administration of HCG. IVF will be performed according to standard practices at our institution. A maximum of three embryos will be transferred 48 h after oocyte retrieval (ESHRE Committee on Good Clinical and Laboratory Practice, 1995 ). Patients will receive micronized progesterone, 600 mg/day, by vaginal administration for at least the first 3 weeks of pregnancy, beginning on the day of embryo transfer.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 and 40
  • Informed consent
  • Indication for IVF-ET

Exclusion Criteria:

  • Inability to understand written informed consent form
  • Personal history of ovarian hyperstimulation syndrome
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00749853

Contacts
Contact: Clemens B. Tempfer, MD +43 1 40400 ext 2915 clemens.tempfer@meduniwien.ac.at

Locations
Austria
University of Vienna Not yet recruiting
Vienna, Austria, A-1090
Contact: Clemens B. Tempfer, MD    +43 1 40400 ext 2915    clemens.tempfer@meduniwien.ac.at   
Principal Investigator: Clemens B. Tempfer, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Study Director: Johannes C. Huber, MD, PhD Medical University of Vienna
  More Information

No publications provided

Responsible Party: Clemens Tempfer, MD, professor, University of Vienna
ClinicalTrials.gov Identifier: NCT00749853     History of Changes
Other Study ID Numbers: ufktem1
Study First Received: September 8, 2008
Last Updated: September 8, 2008
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Medical University of Vienna:
ovarian stimulation
FSH
genotyping
polymorphism

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Buserelin
Hormones
Follicle Stimulating Hormone
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 16, 2014