Clinical trial NCT01196143: A Study to Evaluate the Baseline Follicle Stimulating Hormone, Ovarian Volume and Antral Follicle Count as Prognostic Factors of the Outcome of In-vitro Fertilisation/Intracytosolic Sperm Injection in Infertile Patients Receiving Gonal f for Controlled Ovarian Hyperstimulation
Official title: Non-interventional Observational Study to Evaluate the Baseline FSH, Ovarian Volume and AFC (Antral Follicle Count) as Prognostic Factors of the Outcome of the In-vitro Fertilization/Intracytosolic Sperm Injection (IVF/ICSI) in Infertile Patients Who Receive r-FSH (GONAL-f®) for Controlled Ovarian Hyperstimulation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility
Keywords: Ovulation induction
Intrauterine insemination
Gonal-f
Controlled ovarian stimulation
Female infertility
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-09-08
Enrollment: 356
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects undergoing COH for IVF/ICSI-treatment with Gonal-f in Greece.

Brief summary: This is a phase IV non-interventional, multicentric observational study to evaluate the baseline follicle stimulating hormone (FSH) levels, ovarian volume, antral follicle count (AFC) and age as prognostic factors of the outcome of the in-vitro fertilisation/intracytosolic sperm injection (IVF/ICSI) in infertile subjects receiving Gonal-f for controlled ovarian hyperstimulation (COH).

Detailed description: Treatment of subfertility and infertility by assisted reproduction technologies (ART) such as IVF and embryo transfer (ET) requires multiple follicular development to increase the number of female gametes, and the chances of a successful treatment outcome. These technologies include the stimulation of multiple follicular development by exogenous FSH administration and the suppression of endogenous luteinizing hormone (LH) secretion by administration of a GnRH analogue (antagonist or agonist, as required). A single dose of human chorionic gonadotropin (hCG) is administered to mimic the endogenous LH surge and induce final oocyte maturation after adequate follicular development. Recombinant-hFSH (r-hFSH) has been shown to be efficacious in terms of number of oocytes recovered and in terms of pregnancy rates as compared to urinary-hFSH.

Gonal-f fill-by-mass is available as a liquid formulation that can be administered with the pen device. The pen device is prefilled and hence the subject does not require to assemble the device making it simpler to use. The prefilled pen allows the accurate delivery of a precise dose of r-hFSH in 37.5 International Units (IU) increments.

OBJECTIVES

Primary objective:

* Evaluation of the significance of baseline FSH, ovarian volume and AFC with a model adjusted for age as prognostic factors of the IVF/ICSI treatment outcome.

This study planned to enrol 500 female subjects undergoing COH for IVF/ICSI-treatment with Gonal-f. Gonal-f will be administered daily subcutaneously (s.c.) according to the centre's usual clinical practice, commencing on Days 2 or 3 of the cycle during the stimulation period. Treatment with Gonal-f will be continued until adequate follicular development has been achieved with the dose adjusted according to the subject's response, to usually not higher than 450 IU daily. A single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG would be administered 24-48 hours after the last Gonal-f injection to induce final follicular maturation. Gonal-f will be started approximately 2 weeks after the start of an gonadotrophin-releasing hormone (GnRH) agonist treatment, both being continued until adequate follicular development will be achieved. Oocyte retrieval will be done 34-36 hours after hCG administration followed by IVF/ICSI treatment according to clinic's protocol. Each enrolled subject would be followed up until the confirmation of her pregnancy status. Active follow up of all pregnancies will be performed, including those subjects withdrawn from the study.

Eligibility criteria: Inclusion Criteria:

* Pre-menopausal female subjects aged between 20-43 years
* Subjects requiring treatment with recombinant FSH for COH for IVF and/or ICSI
* Subjects who are able to communicate well with the investigator and can comply with the requirements of the entire study
* Subjects who have given written informed consent, prior to treatment, with the understanding that consent may be withdrawn by the subject at any time without prejudice

Exclusion Criteria:

* Female subjects not pregnant or lactating
* Subjects with known allergic reaction against one of the ingredients
* Subjects with enlarged ovaries or cysts unrelated to polycystic ovarian disease.
* Subjects with gynaecological bleeding of unknown origin
* Subjects with ovarian, uterine, or mammary cancer
* Subjects with hyperprolactinaemia
* Subjects with tumors of the hypothalamus or the pituitary gland

Primary outcomes:
measure: Live birth rate
timeFrame: Up to 28 days after birth
Secondary outcomes:
measure: Pregnancy rate (ongoing, clinical, biochemical)
timeFrame: up to 40 weeks post embryo-transfer
measure: Fertilization rate
timeFrame: 24 hours post oocyte retrieval
measure: Implantation rate
timeFrame: 2 weeks post embryo-transfer
measure: Detailed record of adverse events
timeFrame: Up to 1 year after subject enrollment
measure: Hormone (E2) levels on hCG day
timeFrame: Up to 12 hours prior to hCG administration
measure: Duration of treatment
timeFrame: Up to 12 hours post last FSH injection
measure: Total amount of FSH administered
timeFrame: Up to 1 hour post last FSH injection
measure: Number of oocytes
timeFrame: Up to 1 hour post oocyte retrieval
measure: Miscarriage rate
timeFrame: Up to 12 weeks post embryo-transfer
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Centre of Assisted Reproduction "Embryoland"
Study officials:
affiliation: Merck A.E. Hellas,Greece, an affiliate of MerckKGaA, Darmstadt, Germany
name: Michalis Arvanitis, MD, MSc
role: STUDY_DIRECTOR
References: