Reproductive Techniques, Assisted
Conditions
Keywords
oocyte maduration, oocyte donation, dietary supplement
Brief summary
This study evaluates the effect of pretreatment with a multivitamin supplement with probiotics (Seidivid Ferty4®) on oocyte retrieval in normo-responder patients undergoing controlled ovarian hyperstimulation (COH) for oocyte donation, considering both the total number of oocytes retrieved and the number of mature oocytes retrieved, that is, in metaphase II (MII).
Detailed description
Patients will be recruited on the day they are going to start the egg donation program. The patient will start taking the study treatment (multivitamin supplement with probiotics or placebo) immediately after inclusion and will call the site to initiate the oocyte donation protocol approximately 30 days after enrollment. Throughout the COH period of the protocol the patient will continue taking the study supplement (or placebo), without interruption until the day of the GnRH-agonist trigger. The administration of the agonist will be as a single dose, 36 hours before follicular puncture for the retrieval of mature eggs. Then, the retrieved oocytes will be denuded and examined by light microscopy to assess their quality. The evaluation will carried out by two different embryologists, blinded to the study protocol.
Interventions
DIETARY_SUPPLEMENTSeidivid Ferty4
The patient will start taking the study treatment (multivitamin supplement with probiotics) immediately after inclusion. Throughout the COH period of the protocol (usual mean duration: 11 days) the patient will continue taking the diatary supplement, without interruption until the day of the GnRH-agonist trigger.
OTHERPlacebo
The patient will start taking the study treatment (placebo) immediately after inclusion. Throughout the COH period of the protocol (usual mean duration: 11 days) the patient will continue taking the treatment (placebo), without interruption until the day of the GnRH-agonist trigger.
Sponsors
SEID S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study multivitamin product with probiotics (Seidivid Ferty4®) and placebo will be supplied as capsules with an identical external appearance packaged in blisters in a white box with no label, marked only with the study code and patient code.
Intervention model description
This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a dietary supplement with probiotics, with two parallel group of subjects. Based on previous studies, considering this study as a non-inferiority versus placebo study the calculated sample size of subjects is 210 (105 subject for each arm). Once the informed consent is signed, the patient will be assigned a patient code and will be given the treatment box (white and with no label) corresponding to her code. The patient will start taking the study treatment (multivitamin supplement with probiotics or placebo) immediately after inclusion. Throughout the COH period the patient will continue taking the study supplement and will undergo the regular ultrasound controls of the egg donation program for evolutive control of the number and growth of follicles, without interruption until the day of the GnRH-agonist trigger.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 34 Years
Healthy volunteers
No
Inclusion criteria
* Women undergoing COH for egg donation cycles * Signing of Informed Consent * Age 18-34 years * Body mass index between 18-29.9 kg/m2 * Meet the criteria for inclusion in the oocyte donation program of the Next Fertility center * Ultrasound antral follicle count before COH of ≥15 follicles
Exclusion criteria
* Patients excluded from the oocyte donation program * Untreated sexually transmitted disease, HIV, HCV, HBV positive serology * Blood disorders, neurodegenerative/psychiatric diseases, fragile X syndrome, oncological diseases, endometriosis. * Polycystic ovary syndrome * Oligomenorrhea (\<1 menstrual cycle in 3 months) * Diabetic patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Oocytes Retrieved | Through study completion, an average of 42 days | Total number of oocytes retrieved in the follicular puncture |
| Number of Mature (MII) Oocytes Retrieved | Through study completion, an average of 42 days | Total number of mature oocytes (metaphase II, or MII) retrieved in the follicular puncture |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Follicles at the Time of Trigger Administration | Through trigger administration, an average of 40 days | Ultrasound follicle count at the time of trigger administration |
| Fasting Glucose After 30 Days of Treatment With Dietary Supplement. | Through COH start, an average of 30 days | Fasting blood glucose at the start of controlled ovarian hyperstimulation (COH) |
| AST After 30 Days of Treatment With Dietary Supplement. | Through COH start, an average of 30 days | Serum aspartate aminotransferase (AST) levels at the time of controlled ovarian hyperstimulation (COH) start |
| Number of Good Quality Oocytes | Through study completion, an average of 42 days | Number of oocytes MII without dimorphisms |
| Cholesterol After 30 Days of Treatment With Dietary Supplement. | Through COH start, an average of 30 days | Total cholesterol at the time of controlled ovarian hyperstimulation (COH) start |
| LH at the Time of COH Start | Through COH start, an average of 30 days | Plasma levels of luteinizing hormone (LH) at the time of controlled ovarian hyperstimulation (COH) start |
| ALT After 30 Days of Treatment With Dietary Supplement. | Through COH start, an average of 30 days | Serum alanine aminotransferase (ALT) levels at the time of controlled ovarian hyperstimulation (COH) start |
| Number of Oocytes With Dimorphisms | Through study completion, an average of 42 days | Number of mature oocytes MII with dimorphisms |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Seidivid Ferty4 Patients included in this group will be administered dietary supplement Seidivid Ferty4 (2 capsules per day, as a single dose) for at least 30 days prior to controlled ovarian hyperstimulation and until the day of the agonist trigger (GnRH a). | 98 |
| Placebo Patients included in this group will be administered placebo (2 capsules per day, as a single dose) for at least 30 days prior to controlled ovarian hyperstimulation and until the day of the agonist trigger (GnRH-a). | 98 |
| Total | 196 |
Baseline characteristics
| Characteristic | Placebo | Total | Seidivid Ferty4 |
|---|---|---|---|
| Age, Continuous | 23.10 years STANDARD_DEVIATION 3.24 | 23.58 years STANDARD_DEVIATION 3.71 | 24.06 years STANDARD_DEVIATION 4.09 |
| Baseline ALT | 16.80 U/L STANDARD_DEVIATION 8.26 | 17.26 U/L STANDARD_DEVIATION 9.2 | 17.72 U/L STANDARD_DEVIATION 10.07 |
| Baseline AST | 19.88 U/L STANDARD_DEVIATION 6.42 | 20.60 U/L STANDARD_DEVIATION 10.78 | 21.31 U/L STANDARD_DEVIATION 13.78 |
| Baseline Cholesterol | 164.40 mg/dL STANDARD_DEVIATION 31.29 | 165.16 mg/dL STANDARD_DEVIATION 29.74 | 165.91 mg/dL STANDARD_DEVIATION 29.74 |
| Baseline Cholesterol LDL | 87.83 mg/dl STANDARD_DEVIATION 23.25 | 88.58 mg/dl STANDARD_DEVIATION 22.32 | 89.32 mg/dl STANDARD_DEVIATION 21.48 |
| Baseline Fasting Glucose | 79.91 mg/dl STANDARD_DEVIATION 9.27 | 80.61 mg/dl STANDARD_DEVIATION 8.85 | 81.21 mg/dl STANDARD_DEVIATION 8.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 98 Participants | 196 Participants | 98 Participants |
| Number of Antral Follicles at Study Inclusion | 21.33 antral follicles STANDARD_DEVIATION 4.54 | 21.82 antral follicles STANDARD_DEVIATION 4.65 | 22.30 antral follicles STANDARD_DEVIATION 4.73 |
| Region of Enrollment Spain | 98 participants | 196 participants | 98 participants |
| Sex: Female, Male Female | 98 Participants | 196 Participants | 98 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 / 98 | 0 / 98 |
| other Total, other adverse events | 2 / 98 | 0 / 98 |
| serious Total, serious adverse events | 0 / 98 | 0 / 98 |
Outcome results
Primary
Number of Mature (MII) Oocytes Retrieved
Total number of mature oocytes (metaphase II, or MII) retrieved in the follicular puncture
Time frame: Through study completion, an average of 42 days
Population: Only patients who completed the study and underwent follicular puncture
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Number of Mature (MII) Oocytes Retrieved | 20.41 mature oocytes | Standard Deviation 9.32 |
| Placebo | Number of Mature (MII) Oocytes Retrieved | 18.86 mature oocytes | Standard Deviation 8.47 |
p-value: 0.3582Wilcoxon (Mann-Whitney)
Primary
Number of Oocytes Retrieved
Total number of oocytes retrieved in the follicular puncture
Time frame: Through study completion, an average of 42 days
Population: Only patients who completed the study and underwent follicular puncture
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Number of Oocytes Retrieved | 24.77 oocytes retrieved | Standard Deviation 10.96 |
| Placebo | Number of Oocytes Retrieved | 22.57 oocytes retrieved | Standard Deviation 9.12 |
p-value: 0.2629Wilcoxon (Mann-Whitney)
Secondary
ALT After 30 Days of Treatment With Dietary Supplement.
Serum alanine aminotransferase (ALT) levels at the time of controlled ovarian hyperstimulation (COH) start
Time frame: Through COH start, an average of 30 days
Population: Only patients with ALT data recorded at baseline and at 30 days were analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | ALT After 30 Days of Treatment With Dietary Supplement. | 19.14 U/L | Standard Deviation 8.75 |
| Placebo | ALT After 30 Days of Treatment With Dietary Supplement. | 16.84 U/L | Standard Deviation 6.13 |
p-value: 0.06281t-test, 2 sided
Comparison: ALT at the start of COH compared to baseline ALT.p-value: 0.417757t-test, 2 sided
Comparison: ALT at the start of COH compared to baseline ALT.p-value: 0.968525t-test, 2 sided
Secondary
AST After 30 Days of Treatment With Dietary Supplement.
Serum aspartate aminotransferase (AST) levels at the time of controlled ovarian hyperstimulation (COH) start
Time frame: Through COH start, an average of 30 days
Population: Only patients with AST data recorded at baseline and at 30 days were analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | AST After 30 Days of Treatment With Dietary Supplement. | 20.38 U/L | Standard Deviation 5.79 |
| Placebo | AST After 30 Days of Treatment With Dietary Supplement. | 20.37 U/L | Standard Deviation 6.14 |
p-value: 0.59695t-test, 2 sided
Comparison: AST at the start of COH compared to baseline AST.p-value: 0.466503t-test, 2 sided
Comparison: AST at the start of COH compared to baseline AST.p-value: 0.959877t-test, 2 sided
Secondary
Cholesterol After 30 Days of Treatment With Dietary Supplement.
Total cholesterol at the time of controlled ovarian hyperstimulation (COH) start
Time frame: Through COH start, an average of 30 days
Population: Only patients with total cholesterol data recorded at baseline and at 30 days were analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Cholesterol After 30 Days of Treatment With Dietary Supplement. | 167.89 mg/dl | Standard Deviation 29.66 |
| Placebo | Cholesterol After 30 Days of Treatment With Dietary Supplement. | 170.17 mg/dl | Standard Deviation 31.33 |
p-value: 0.686488t-test, 2 sided
Comparison: Cholesterol at the start of COH compared to baseline cholesterol.p-value: 0.39512t-test, 2 sided
Comparison: Cholesterol at the start of COH compared to baseline cholesterol.p-value: 0.127135t-test, 2 sided
Secondary
Fasting Glucose After 30 Days of Treatment With Dietary Supplement.
Fasting blood glucose at the start of controlled ovarian hyperstimulation (COH)
Time frame: Through COH start, an average of 30 days
Population: Only patients with fasting glucose data recorded at baseline and at 30 days were analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Fasting Glucose After 30 Days of Treatment With Dietary Supplement. | 81.49 mg/dl | Standard Deviation 13.04 |
| Placebo | Fasting Glucose After 30 Days of Treatment With Dietary Supplement. | 82.48 mg/dl | Standard Deviation 9.02 |
p-value: 0.9214t-test, 2 sided
Comparison: Fasting glucose at the start of COH compared to baseline fasting glucose.p-value: 0.042t-test, 2 sided
Comparison: Fasting glucose at the start of COH compared to baseline fasting glucose.p-value: <0.001t-test, 2 sided
Secondary
LH at the Time of COH Start
Plasma levels of luteinizing hormone (LH) at the time of controlled ovarian hyperstimulation (COH) start
Time frame: Through COH start, an average of 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | LH at the Time of COH Start | 6.55 mUI/ml | Standard Deviation 4.16 |
| Placebo | LH at the Time of COH Start | 5.69 mUI/ml | Standard Deviation 3.96 |
p-value: 0.257496t-test, 2 sided
Secondary
Number of Follicles at the Time of Trigger Administration
Ultrasound follicle count at the time of trigger administration
Time frame: Through trigger administration, an average of 40 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Number of Follicles at the Time of Trigger Administration | 28.01 follicle count | Standard Deviation 10.41 |
| Placebo | Number of Follicles at the Time of Trigger Administration | 24.8 follicle count | Standard Deviation 7.08 |
p-value: 0.0314Wilcoxon (Mann-Whitney)
Secondary
Number of Good Quality Oocytes
Number of oocytes MII without dimorphisms
Time frame: Through study completion, an average of 42 days
Population: Only patients who completed the study underwent follicular puncture and retrieved MII oocytes. One case was excluded because no mature oocytes were retrieved.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Number of Good Quality Oocytes | 17.00 oocytes | Standard Deviation 7.67 |
| Placebo | Number of Good Quality Oocytes | 15.43 oocytes | Standard Deviation 8.2 |
p-value: 0.2187Wilcoxon (Mann-Whitney)
Secondary
Number of Oocytes With Dimorphisms
Number of mature oocytes MII with dimorphisms
Time frame: Through study completion, an average of 42 days
Population: Only patients who completed the study and underwent follicular puncture, and who specified whether the oocytes had dysmorphisms. One case was excluded because no mature oocytes were obtained, and three cases were excluded because the number of dysmorphic oocytes was not specified.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seidivid Ferty4 | Number of Oocytes With Dimorphisms | 3.71 oocytes | Standard Deviation 4.41 |
| Placebo | Number of Oocytes With Dimorphisms | 3.46 oocytes | Standard Deviation 4.66 |
p-value: 0.3005Wilcoxon (Mann-Whitney)