In Vitro Fertilization
Conditions
Keywords
Luteal Phase Support in IVF patients
Brief summary
Prospective, open, randomised, parallel, multicentre, two arm trial comparing a new form of luteal support (S.C.) to an approved comparator (vaginal gel).
Interventions
DRUGProgesterone
25 mg, s.c., once à day
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Age 18- 42 (upon starting COH); * BMI \<30 kg/m2; * \<3 prior ART cycles (IVF, ICSI and related procedures); * Baseline (day 2-3 of cycling) FSH \<15 IU/L and E2 \<80 pg/mL; * Normal uterine cavity as per recent hysterosalpingogram, sonohysterogram or hysteroscopic exam (i.e. no polyp or protruding sub-mucosal fibroid); * At least 3 retrieved oocytes; * Patient has given written informed consent.
Exclusion criteria
* Intramural uterine fibroids that distort the uterine cavity or polyps \>1 cm; * Stage III or IV endometriosis (endometriomas); * Hydrosalpinx; * History of past poor response to COH resulting in canceling ART; * Use of thawed/donated oocytes; * Use of thawed/donated embryos; * Patients affected by pathologies associated with any contraindication of being pregnant; * Hypersensitivity to study medication; * Uncontrolled adrenal or thyroid dysfunction; * Undiagnosed vaginal bleeding; * History of arterial disease; * Patients with hepatic impairment; * Neoplasias (current) or history of neoplasia that may be responsive to progesterone; * High grade cervical dysplasia; * Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders; * History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages wherein pregnancy developed to a minimum of a gestational sac on TVUS; * Participation in a concurrent clinical trial or another trial within the past 2 months; * Use of concomitant medications that might interfere with the study evaluation; * Pre-implantation genetic diagnosis/screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ongoing Pregnancy Rate at the End of the Study | 10 weeks after treatment start |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delivery Rate and Live Birth Rate | nearly 9 month after treatment start | — |
| Implantation Rate | Four to five weeks after oocytes retrieval | Implantation rate was defined as the mean of the total number of gestational sacs seen divided by the total number of embryos transferred. Values are reported as a percentage. |
Countries
Germany, Hungary, Italy, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Progesterone SC Progesterone SC was administered at a daily dosage of 25 mg during a minimum of two weeks (in case of no pregnancy) to a maximum of 10 weeks (in case of pregnancy) | 339 |
| Progesterone Vaginal Gel Progesterone Vaginal gel was administered at a daily dosage of 90 mg during a minimum of two weeks (in case of no pregnancy) to a maximum of 10 weeks (in case of pregnancy) | 344 |
| Total | 683 |
Baseline characteristics
| Characteristic | Progesterone SC | Progesterone Vaginal Gel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 339 Participants | 344 Participants | 683 Participants |
| Age Continuous | 33.8 years STANDARD_DEVIATION 4.3 | 33.9 years STANDARD_DEVIATION 4.3 | 33.8 years STANDARD_DEVIATION 4.3 |
| Region of Enrollment Germany | 24 participants | 23 participants | 47 participants |
| Region of Enrollment Hungary | 64 participants | 64 participants | 128 participants |
| Region of Enrollment Italy | 157 participants | 162 participants | 319 participants |
| Region of Enrollment Switzerland | 48 participants | 50 participants | 98 participants |
| Region of Enrollment United Kingdom | 46 participants | 45 participants | 91 participants |
| Sex: Female, Male Female | 339 Participants | 344 Participants | 683 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 | — / — | — / — |
| other Total, other adverse events | 168 / 338 | 157 / 344 |
| serious Total, serious adverse events | 14 / 338 | 20 / 344 |
Outcome results
Primary
Ongoing Pregnancy Rate at the End of the Study
Time frame: 10 weeks after treatment start
Population: ITT population was analysed (i.e. all the randomised patients)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone SC | Ongoing Pregnancy Rate at the End of the Study | 27.4 percentage of randomized patient |
| Progesterone Vaginal Gel | Ongoing Pregnancy Rate at the End of the Study | 30.5 percentage of randomized patient |
Comparison: The non -inferiority hypothesis to be tested for the primary endpoint was that the ongoing pregnancy rate (oPR) in the test group (Pe)was lower than the oPR in the control group (Pc)against the alternative one that the oPR in the test group was equal to or higher than the oPR in the control group.~H0 : Pc\>= Pe + d(-10%) H1 : Pc\< Pe + d(-10%)p-value: 0.3795% CI: [-9.9, 3.7]Chi-squared
Secondary
Delivery Rate and Live Birth Rate
Time frame: nearly 9 month after treatment start
Population: all the randomised patients were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone SC | Delivery Rate and Live Birth Rate | 26.8 percentage of randomised patients |
| Progesterone Vaginal Gel | Delivery Rate and Live Birth Rate | 29.9 percentage of randomised patients |
p-value: 0.3795% CI: [-9.87, 3.68]Chi-squared
Secondary
Implantation Rate
Implantation rate was defined as the mean of the total number of gestational sacs seen divided by the total number of embryos transferred. Values are reported as a percentage.
Time frame: Four to five weeks after oocytes retrieval
Population: All the patients who had at least one embryo transferred
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Progesterone SC | Implantation Rate | 22.6 percentage of embryos transferred | Standard Deviation 35 |
| Progesterone Vaginal Gel | Implantation Rate | 23.1 percentage of embryos transferred | Standard Deviation 33.1 |
p-value: 0.8595% CI: [-4.7, 5.8]t-test, 2 sided