Clinical trial NCT00749853: Efficacy of Ovarian Stimulation Based on FSHR Genotype Status
Official title: Prospective, Randomized Open Trial to Evaluate the Efficacy of an Ovarian Stimulation Protocol Based on FSH Receptor Genotype
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Sterility
Keywords: ovarian stimulation
FSH
genotyping
polymorphism
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2008-09-09
Enrollment: 165
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: clinical pregnancy rate
timeFrame: 3 months
Secondary outcomes:
measure: follicle count, cycle cancellation rate, poor responder rate
timeFrame: 2 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Johannes C. Huber, MD, PhD
role: STUDY_DIRECTOR
References: