Reproductive Issues, Reproductive Disorder, Fertility Disorders, Fertility Issues, Gynecologic Disease, IVF
Conditions
Keywords
follitropin alpha, follicle-stimulating hormone, in vitro fertilization, assisted reproductive technologies, biosimilar, follitropin alfa, real-world data
Brief summary
Aim to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.
Detailed description
A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.
Interventions
DRUGFollitropin Alfa
Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH or agonist of GnRH.
DRUGFollicle Stimulating Hormone/Luteinizing Hormone
Subcutaneous injection of follitropin alpha biosimilar, with daily dose 100-300 IU for at least 5 days, than added another gonadotropin for a maximum of 10 days, using antagonists of GnRH or agonist of GnRH.
Sponsors
Institute for Preventive and Social Medicine
IVFarma LLC
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 43 Years
Healthy volunteers
No
Inclusion criteria
* Women with established causes of infertility and indications for the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation On the use of assisted reproductive technologies, contraindications and limitations to their use No. 107 n dated August 30, 2012. * Infertility due to female and/or male factor. * Presence of ovaries accessible for aspiration of follicles. * Anatomical and functional capability of uterus to bear pregnancy.
Exclusion criteria
* Women with established contraindications to the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation On the use of assisted reproductive technologies, contraindications and limitations to their use No. 107 n dated August 30, 2012. * Presence of pregnancy * Hypersensitivity to follitropin alfa or excipients. * Ovarian cysts (not associated with polycystic ovarian syndrome), uterine hemorrhage of unclear etiology * Premature ovarian failure * Presence of clinically significant systemic disease * Presence of chronic cardiovascular, hepatic, renal or pulmonary disease * Neoplasia * Narcomania, alcoholism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Oocytes Retrieved | From date of start of ovarian stimulation with follitropin alpha up to 15 days | The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the ovulation inducer (HCG or GnRH-agonist). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646). |
| Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | At least 6 weeks after embryo transfer | Ongoing clinical pregnancy per embryo transfer (detection of gestational sac and heartbeat from 6 weeks after transfer), n (ongoing pregnancy rate per transfer with known outcome, %). Due to delayed embryo transfers, the analysed population for Ongoing clinical pregnancy per embryo transfer was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2007 embryo transfers (1542 with known outcome); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2213 embryo transfers (1800 with known outcome); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 1809 embryo transfers (1466 with known outcome) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 404 embryo transfers (334 with known outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Mature Oocytes | From date of start of ovarian stimulation with follitropin alpha up to 15 days | Mature oocytes (MII stage of development). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646). |
| Number of Fertilized Oocytes | From date of start of ovarian stimulation with follitropin alpha up to 16 days | Fertilization rate (FR) is percentage of transformation of oocytes into two pronuclei (presence of two pronuclei: zygotes with 2PN). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646). |
| Total Dose of Follitropin Alpha Biosimilar Protocol, IU | From date of start of ovarian stimulation with follitropin alpha up to 16 days | Mean dose of follitropin alpha biosimilar for ovarian stimulation. Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646). |
Countries
Russia
Participant flow
Recruitment details
All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins.
Participants by arm
| Arm | Count |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH The OS protocols included: mixed protocols (recombinant with addition of urinary-derived gonadotropins) and antagonists/agonists of GnRH (ganirelix, cetrorelix, triptorelin, buserelin), where follitropin alpha biosimilar used for at least 5 days during OS.
Follicle Stimulating Hormone/Luteinizing Hormone: Subcutaneous injection of follitropin alpha biosimilar, with daily dose 100-300 IU for at least 5 days, than added another gonadotropin for a maximum of 10 days, using antagonists of GnRH or agonist of GnRH. | 2,625 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH The OS protocols included: monotherapy protocols with using only follitropin alpha biosimilar and antagonists of GnRH.
Follitropin Alfa: Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH only for suppression. | 2,183 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH The OS protocol included: monotherapy protocols with using only follitropin alpha biosimilar and agonists of GnRH.
Follitropin Alfa: Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using agonists of GnRH only for suppression. | 676 |
| Total | 5,484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 78 | 59 | 30 |
Baseline characteristics
| Characteristic | Total | Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH |
|---|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 4.8 | 34.9 years STANDARD_DEVIATION 4.8 | 32.9 years STANDARD_DEVIATION 4.6 | 33.1 years STANDARD_DEVIATION 4.9 |
| Body Mass Index (BMI), kg/m^2 | 23.8 kg/m^2 STANDARD_DEVIATION 5.7 | 23.9 kg/m^2 STANDARD_DEVIATION 4.7 | 23.7 kg/m^2 STANDARD_DEVIATION 4.6 | 23.1 kg/m^2 STANDARD_DEVIATION 4.5 |
| Duration of infertility, years | 5.6 years STANDARD_DEVIATION 4.2 | 5.7 years STANDARD_DEVIATION 4.1 | 5.4 years STANDARD_DEVIATION 4.3 | 5.6 years STANDARD_DEVIATION 3.8 |
| IVF attempt | 1.3 number of IVF attempts STANDARD_DEVIATION 0.7 | 1.4 number of IVF attempts STANDARD_DEVIATION 0.7 | 1.2 number of IVF attempts STANDARD_DEVIATION 0.5 | 1.4 number of IVF attempts STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5484 Participants | 2625 Participants | 2183 Participants | 676 Participants |
| Region of Enrollment Russia | 5484 participants | 2625 participants | 2183 participants | 676 participants |
| Sex: Female, Male Female | 5484 Participants | 2625 Participants | 2183 Participants | 676 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5,484 |
| other Total, other adverse events | 657 / 5,484 |
| serious Total, serious adverse events | 0 / 5,484 |
Outcome results
Primary
Number of Oocytes Retrieved
The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the ovulation inducer (HCG or GnRH-agonist). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Time frame: From date of start of ovarian stimulation with follitropin alpha up to 15 days
Population: Arm Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH is combined group for primary and secondary outcome measures and consist of patients from Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH and Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Number of Oocytes Retrieved | 8.6 The total number of retrieved oocytes | Standard Deviation 6.8 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | Number of Oocytes Retrieved | 10.3 The total number of retrieved oocytes | Standard Deviation 7.4 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Number of Oocytes Retrieved | 10.5 The total number of retrieved oocytes | Standard Deviation 7.5 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | Number of Oocytes Retrieved | 9.6 The total number of retrieved oocytes | Standard Deviation 7 |
| The Overall Protocols | Number of Oocytes Retrieved | 9.5 The total number of retrieved oocytes | Standard Deviation 7.2 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.032Wilcoxon (Mann-Whitney)
Primary
Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer
Ongoing clinical pregnancy per embryo transfer (detection of gestational sac and heartbeat from 6 weeks after transfer), n (ongoing pregnancy rate per transfer with known outcome, %). Due to delayed embryo transfers, the analysed population for Ongoing clinical pregnancy per embryo transfer was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2007 embryo transfers (1542 with known outcome); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2213 embryo transfers (1800 with known outcome); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 1809 embryo transfers (1466 with known outcome) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 404 embryo transfers (334 with known outcome).
Time frame: At least 6 weeks after embryo transfer
Population: Arm Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH is combined group for primary and secondary outcome measures and consist of patients from Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH and Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | 39.3 Percetnage of patients (%) |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | 37.6 Percetnage of patients (%) |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | 37.9 Percetnage of patients (%) |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | 35.9 Percetnage of patients (%) |
| The Overall Protocols | Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer | 38.4 Percetnage of patients (%) |
Comparison: 95% Confidence intervals (CIs) of point estimates were calculated using the exact binominal distribution (Clopper-Pearson method) for proportionsp-value: 0.31495% CI: [-0.0161, 0.0501]Chi-squared
Comparison: 95% Confidence intervals (CIs) of point estimates were calculated using the exact binominal distribution (Clopper-Pearson method) for proportionsp-value: 0.48295% CI: [-0.0369, 0.0782]Chi-squared
Secondary
Number of Fertilized Oocytes
Fertilization rate (FR) is percentage of transformation of oocytes into two pronuclei (presence of two pronuclei: zygotes with 2PN). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Time frame: From date of start of ovarian stimulation with follitropin alpha up to 16 days
Population: Arm Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH is combined group for primary and secondary outcome measures and consist of patients from Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH and Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Number of Fertilized Oocytes | 5.8 zygotes with 2PN | Standard Deviation 5.2 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | Number of Fertilized Oocytes | 7.2 zygotes with 2PN | Standard Deviation 6.2 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Number of Fertilized Oocytes | 7.3 zygotes with 2PN | Standard Deviation 6.3 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | Number of Fertilized Oocytes | 5.7 zygotes with 2PN | Standard Deviation 5 |
| The Overall Protocols | Number of Fertilized Oocytes | 6.1 zygotes with 2PN | Standard Deviation 5.8 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Mature Oocytes
Mature oocytes (MII stage of development). Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Time frame: From date of start of ovarian stimulation with follitropin alpha up to 15 days
Population: Arm Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH is combined group for primary and secondary outcome measures and consist of patients from Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH and Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Number of Mature Oocytes | 6.7 Number of mature oocytes | Standard Deviation 6.2 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | Number of Mature Oocytes | 7.7 Number of mature oocytes | Standard Deviation 6.9 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Number of Mature Oocytes | 7.6 Number of mature oocytes | Standard Deviation 6.9 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | Number of Mature Oocytes | 6.7 Number of mature oocytes | Standard Deviation 5.7 |
| The Overall Protocols | Number of Mature Oocytes | 6.8 Number of mature oocytes | Standard Deviation 6.6 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Total Dose of Follitropin Alpha Biosimilar Protocol, IU
Mean dose of follitropin alpha biosimilar for ovarian stimulation. Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).
Time frame: From date of start of ovarian stimulation with follitropin alpha up to 16 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 1672 IU (International Units) | Standard Deviation 568 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 1919 IU (International Units) | Standard Deviation 639 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 1952 IU (International Units) | Standard Deviation 621 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 1711 IU (International Units) | Standard Deviation 680 |
| The Overall Protocols | Total Dose of Follitropin Alpha Biosimilar Protocol, IU | 1825 IU (International Units) | Standard Deviation 647 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)