Efficacy of Ovarian Stimulation Based on FSHR Genotype Status

NCT ID: NCT00749853

Last Updated: 2015-05-05

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 165 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2015-06-30

Brief Summary

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).

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.

Conditions

Sterility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

follicle stimulating hormone

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

follicle stimulating hormone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

buserelin, r-hFSH, r-hLH; buserelin, r-hFSH, HCG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Clemens Tempfer

Prof. Clemens Tempfer, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johannes C. Huber, MD, PhD

Role: STUDY_DIRECTOR

Medical University of Vienna

Locations

University of Vienna

Vienna, Vienna, Austria

Countries

Austria

Other Identifiers

ufktem1

Identifier Type: -

Identifier Source: org_study_id