Infertility
Conditions
Keywords
In vitro fertilization (IVF), Assisted reproduction technologies (ART), GnRH-antagonist, Follicle stimulating hormone (FSH)
Brief summary
The purpose of the non-inferiority study is to evaluate the clinical efficacy and the safety of two different subcutaneous FSH preparations (Fostimon versus Gonal-F) for controlled ovarian hyperstimulation in a GnRH-antagonist cycle.
Interventions
DRUGUrofollitrophin
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-38 years old; * BMI: 18-28 kg/m2; * Less than 3 previously completed IVF cycles; * Basal FSH \<10 IU/L and E2 \<80 pg/ml; * TSH \< 2.5 mIU/L * \>10 and \<30 antral follicles 2-10 mm in size for both ovaries combined * AMH: \>1 ng/ml (7.15 pmol/l) and \<5.6 ng/ml (40.0 pmol/l) * Presence and adequate visualization of both ovaries; * Within 12 months of the beginning of the study, uterine cavity consistent with expected normal function as assessed through transvaginal ultrasound, hysterosalpingogram, sonohysterogram or hysteroscopic examination;
Exclusion criteria
* Primary ovarian failure or women known as poor responders; * PCO and PCOS; * Severe OHSS in a previous COH cycle; * Uterine malformation that may impair the possibility to get pregnant; * Ovarian cysts \>10 mm; * Hydrosalpinx that have not been surgically removed or ligated; * Endometriosis stage 3 or 4; * Oocyte donation; * Severe male factor; * Pathologies associated with any contraindication of being pregnant; * History of recurrent miscarriage (more than 3 previous miscarriages); * Hypersensitivity to the study medication; * Abnormal bleeding of undetermined origin; * Uncontrolled thyroid or adrenal dysfunction; * Neoplasias; * Severe impairment of renal and/or hepatic function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pregnancy Rate | 8 weeks | A clinical pregnancy is defined as a pregnancy showing ultrasound embryonic heart activity at 8 weeks of gestation; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Oocytes Retrieved | end of treatment period, approximately 2 - 3 weeks. | — |
| Fertilization Rate | end of treatment period, approximately 2 - 3 weeks | — |
| Embryo Quality (Number of Top Quality Embryos Transferred Per Patient) | On culture day 3 | The embryo quality evaluation will be performed on culture day 3, just before embryo transfer and will consist in the assessment of blastomeres number and 2 embryo morphology parameters: degree of fragmentation and cell division aspect. |
| Number of Follicles >16 mm on the Day of hCG Injection | 10-15 days after starting FSH stimulation | — |
| Delivery Rate | 9 months | — |
| Cumulative Pregnancy Rate | 2 years | Patients who will not get pregnant during the study, will be allowed to perform a frozen embryo transfer. Cumulative pregnancy rate will include also pregnancies achieved after a frozen embryo transfer. |
| Positive Serum Pregnancy Test Rate | 2 weeks after embryo transfer | Two weeks after embryo transfer, a serum pregnancy test will be performed. |
Countries
Belgium, Italy, Spain, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fostimon® 75 IU/vial, powder and solvent for solution for subcutaneous injection (Follicle Stimulating Hormone,IBSA Institut Biochimique SA)
Urofollitrophin | 352 |
| Gonal-F® 75 IU/vial powder and solvent for solution for subcutaneous injection (Follicle Stimulating Hormone; Merck Serono)
Follitrophin alpha | 358 |
| Total | 710 |
Baseline characteristics
| Characteristic | Fostimon® | Gonal-F® | Total |
|---|---|---|---|
| Age, Continuous | 32.39 years STANDARD_DEVIATION 3.83 | 32.68 years STANDARD_DEVIATION 3.52 | 32.53 years STANDARD_DEVIATION 3.5 |
| Race/Ethnicity, Customized Race American Indian or Alaska native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 13 Participants | 14 Participants | 27 Participants |
| Race/Ethnicity, Customized Race Black | 2 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Race White | 336 Participants | 339 Participants | 675 Participants |
| Region of Enrollment Belgium | 39 participants | 41 participants | 80 participants |
| Region of Enrollment Italy | 91 participants | 88 participants | 179 participants |
| Region of Enrollment Spain | 99 participants | 101 participants | 200 participants |
| Region of Enrollment Switzerland | 24 participants | 25 participants | 49 participants |
| Region of Enrollment Turkey | 55 participants | 59 participants | 114 participants |
| Region of Enrollment United Kingdom | 44 participants | 44 participants | 88 participants |
| Sex: Female, Male Female | 352 Participants | 358 Participants | 710 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 352 | 0 / 358 |
| other Total, other adverse events | 36 / 352 | 42 / 358 |
| serious Total, serious adverse events | 24 / 352 | 31 / 358 |
Outcome results
Primary
Clinical Pregnancy Rate
A clinical pregnancy is defined as a pregnancy showing ultrasound embryonic heart activity at 8 weeks of gestation;
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fostimon® | Clinical Pregnancy Rate | 36.93 percentage of participants |
| Gonal-F® | Clinical Pregnancy Rate | 39.66 percentage of participants |
p-value: 0.4995% CI: [-9.88, 4.42]Fisher Exact
Secondary
Cumulative Pregnancy Rate
Patients who will not get pregnant during the study, will be allowed to perform a frozen embryo transfer. Cumulative pregnancy rate will include also pregnancies achieved after a frozen embryo transfer.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fostimon® | Cumulative Pregnancy Rate | 45.2 percentage of participants |
| Gonal-F® | Cumulative Pregnancy Rate | 52.0 percentage of participants |
p-value: 0.07Fisher Exact
Secondary
Delivery Rate
Time frame: 9 months
Population: For 4 patients, 3 allocated to the Fostimon® group and 1 allocated to the Gonal-F® group this information was not available because of lost to follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fostimon® | Delivery Rate | 34.4 percentage of participants |
| Gonal-F® | Delivery Rate | 36.7 percentage of participants |
p-value: 0.53Fisher Exact
Secondary
Embryo Quality (Number of Top Quality Embryos Transferred Per Patient)
The embryo quality evaluation will be performed on culture day 3, just before embryo transfer and will consist in the assessment of blastomeres number and 2 embryo morphology parameters: degree of fragmentation and cell division aspect.
Time frame: On culture day 3
Population: Subject with at least one embryo transferred, with embryo scoring available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostimon® | Embryo Quality (Number of Top Quality Embryos Transferred Per Patient) | 0.47 Top embryos | Standard Deviation 0.64 |
| Gonal-F® | Embryo Quality (Number of Top Quality Embryos Transferred Per Patient) | 0.48 Top embryos | Standard Deviation 0.64 |
p-value: 0.89ANOVA
Secondary
Fertilization Rate
Time frame: end of treatment period, approximately 2 - 3 weeks
Population: subjects with at least one oocyte inseminated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostimon® | Fertilization Rate | 73.98 percentage of oocytes | Standard Deviation 26.44 |
| Gonal-F® | Fertilization Rate | 75.85 percentage of oocytes | Standard Deviation 21.48 |
p-value: 0.32ANOVA
Secondary
Number of Follicles >16 mm on the Day of hCG Injection
Time frame: 10-15 days after starting FSH stimulation
Population: Subject with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostimon® | Number of Follicles >16 mm on the Day of hCG Injection | 4.10 follicles >16 mm | Standard Deviation 2.47 |
| Gonal-F® | Number of Follicles >16 mm on the Day of hCG Injection | 4.47 follicles >16 mm | Standard Deviation 2.33 |
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Positive Serum Pregnancy Test Rate
Two weeks after embryo transfer, a serum pregnancy test will be performed.
Time frame: 2 weeks after embryo transfer
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fostimon® | Positive Serum Pregnancy Test Rate | 47.2 percentage of participants |
| Gonal-F® | Positive Serum Pregnancy Test Rate | 49.7 percentage of participants |
p-value: 0.5Fisher Exact
Secondary
Total Number of Oocytes Retrieved
Time frame: end of treatment period, approximately 2 - 3 weeks.
Population: subjects who underwent oocytes retrieval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostimon® | Total Number of Oocytes Retrieved | 8.45 oocytes | Standard Deviation 4.72 |
| Gonal-F® | Total Number of Oocytes Retrieved | 9.33 oocytes | Standard Deviation 4.9 |
p-value: 0.02ANOVA