Embryo Culture Media, Embryo Morphokinetics, Embryonic Mosaicism, Infertility
Conditions
Brief summary
Embryonic aneuploidy is the underlying etiology for the majority of failed implantation and miscarriage. Preimplantation genetic screening (PGS) with transfer of a euploid embryo has been advocated as a strategy for increasing live birth rates with a single embryo transfer. Culturing embryos to the blastocyst stage for trophectoderm biopsy is a requirement for PGS. Several commercially-available single-step embryonic culture media with varying composition have been established for use in the IVF laboratory. Early reports have suggested differences in clinical outcomes, such as aneuploidy and miscarriage rates, with distinct culture media currently in standard use. However, there have been no clinical trials demonstrating the superiority of any one commercially-available culture media formulation. As a result, clinics use media with varying composition based upon familiarity and cost.
Interventions
DEVICEEmbryoScope Plus
All embryos will be cultured in the EmbryoScope Plus to obtain morphokinetic data
OTHERGLOBAL MEDIA
Embryos will be cultured in GLOBAL media
OTHERSAGE MEDIA
Embryos will be cultured in SAGE media
Sponsors
University of California, San Francisco
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
sibling embryo study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
All subjects planning blastocyst culture for preimplantation genetic screening (PGS) will be offered enrollment. Antral Follicle Count (AFC) \>8 Male and female partner \> 18 years of age
Exclusion criteria
Female partner age \>42 years of age Cleavage stage biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aneuploidy Rates | Preimplantation Genetic Testing at blastocyst stage of embryo development, 2 weeks from start of IVF treatment | number of embryos with abnormal chromosome number over total number of embryos biopsied (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Embryo Quality | 2 weeks from start of IVF treatment | Fraction of freezable quality embryos (6 cells or greater, grades 1-2 for symmetry and fragmentation), (%). |
| Embryonic Mosaicism | Preimplantation Genetic Testing at blastocyst stage of embryo development, 2 weeks from start of IVF treatment | Fraction of embryos given mosaic diagnosis. Embryonic mosaicism is defined as having partial aneuploidy (20-80% aneuploid). Low-level mosaicism is defined as 20-40% whereas high-level mosaicism is defined as 40-80%. |
| Embryo Morphokinetics | 2 weeks from start of IVF treatment | time to first and all subsequent cell cleavages |
Countries
United States
Participant flow
Recruitment details
Enrollment occurred between February 2018 and November 2019. All individuals planning in vitro fertilization with intent for blastocyst culture and PGT-A at UCSF Center for Reproductive Health were offered enrollment prior to their treatment cycle
Pre-assignment details
Of 200 subjects enrolled, 1 subject was pregnant before her planned IVF cycle, 8 subjects were canceled prior to retrieval, 3 chose to withdraw from the study, 11 were found to be ineligible and 1 was withdrawn by study personnel due to the conversion to an oocyte cryopreservation cycle. As a result, 176 subjects underwent egg retrieval. Of these, 49 were removed from analysis for not having paired embryos and 127 had paired embryo sets in each culture arm and were able to complete the study.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants had paired embryo sets in each culture arm (SAGE Media or GLOBAL Media). | 127 |
| All Study Participants All study participants had paired embryo sets in each culture arm (SAGE Media or GLOBAL Media). | 127 |
| Total | 254 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 127 Participants |
| Region of Enrollment United States | 127 participants |
| Sex: Female, Male Female | 127 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 127 | 0 / 127 |
| other Total, other adverse events | 0 / 127 | 0 / 127 |
| serious Total, serious adverse events | 0 / 127 | 0 / 127 |
Outcome results
Primary
Aneuploidy Rates
number of embryos with abnormal chromosome number over total number of embryos biopsied (%)
Time frame: Preimplantation Genetic Testing at blastocyst stage of embryo development, 2 weeks from start of IVF treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE Media | Aneuploidy Rates | 56.1 percentage of embryos | Standard Deviation 34.4 |
| GLOBAL Media | Aneuploidy Rates | 62.3 percentage of embryos | Standard Deviation 34 |
p-value: 0.07Wilcoxon signed-rank testing
Secondary
Embryo Morphokinetics
time to first and all subsequent cell cleavages
Time frame: 2 weeks from start of IVF treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE Media | Embryo Morphokinetics | Morula Formation | 92 Hours | Standard Deviation 8.9 |
| SAGE Media | Embryo Morphokinetics | 4 cell formation | 40.6 Hours | Standard Deviation 5.3 |
| SAGE Media | Embryo Morphokinetics | 8 cell formation | 61.9 Hours | Standard Deviation 8.7 |
| SAGE Media | Embryo Morphokinetics | 5 cell formation | 50.6 Hours | Standard Deviation 6.5 |
| SAGE Media | Embryo Morphokinetics | Start of Blastulation | 102.6 Hours | Standard Deviation 8.1 |
| SAGE Media | Embryo Morphokinetics | 6 cell formation | 54.5 Hours | Standard Deviation 8.3 |
| SAGE Media | Embryo Morphokinetics | 7 cell formation | 58.2 Hours | Standard Deviation 8.1 |
| SAGE Media | Embryo Morphokinetics | Blastocyst Formation | 110.6 Hours | Standard Deviation 7.8 |
| SAGE Media | Embryo Morphokinetics | 2 cell formation | 28.1 Hours | Standard Deviation 3.9 |
| SAGE Media | Embryo Morphokinetics | Expanded Blastocyst Formation | 120.3 Hours | Standard Deviation 8.1 |
| SAGE Media | Embryo Morphokinetics | 3 cell formation | 38.5 Hours | Standard Deviation 6.6 |
| GLOBAL Media | Embryo Morphokinetics | Expanded Blastocyst Formation | 122.5 Hours | Standard Deviation 8.2 |
| GLOBAL Media | Embryo Morphokinetics | 7 cell formation | 58.8 Hours | Standard Deviation 8.6 |
| GLOBAL Media | Embryo Morphokinetics | 8 cell formation | 62.5 Hours | Standard Deviation 9 |
| GLOBAL Media | Embryo Morphokinetics | Morula Formation | 93.4 Hours | Standard Deviation 8.6 |
| GLOBAL Media | Embryo Morphokinetics | 2 cell formation | 28.4 Hours | Standard Deviation 4.3 |
| GLOBAL Media | Embryo Morphokinetics | 3 cell formation | 39.5 Hours | Standard Deviation 6.6 |
| GLOBAL Media | Embryo Morphokinetics | 4 cell formation | 41.2 Hours | Standard Deviation 6 |
| GLOBAL Media | Embryo Morphokinetics | 5 cell formation | 52.3 Hours | Standard Deviation 8.2 |
| GLOBAL Media | Embryo Morphokinetics | Start of Blastulation | 104 Hours | Standard Deviation 8.2 |
| GLOBAL Media | Embryo Morphokinetics | Blastocyst Formation | 111.8 Hours | Standard Deviation 7.6 |
| GLOBAL Media | Embryo Morphokinetics | 6 cell formation | 55.4 Hours | Standard Deviation 7.6 |
p-value: 0.01Wilcoxon signed-rank testing
Secondary
Embryonic Mosaicism
Fraction of embryos given mosaic diagnosis. Embryonic mosaicism is defined as having partial aneuploidy (20-80% aneuploid). Low-level mosaicism is defined as 20-40% whereas high-level mosaicism is defined as 40-80%.
Time frame: Preimplantation Genetic Testing at blastocyst stage of embryo development, 2 weeks from start of IVF treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE Media | Embryonic Mosaicism | Low Mosaic expression rate (20-40%) | 1.0 percentage of embryos | Standard Deviation 5.9 |
| SAGE Media | Embryonic Mosaicism | High Mosaic expression rate (40-80%) | 15.9 percentage of embryos | Standard Deviation 25.7 |
| GLOBAL Media | Embryonic Mosaicism | Low Mosaic expression rate (20-40%) | 2.2 percentage of embryos | Standard Deviation 9 |
| GLOBAL Media | Embryonic Mosaicism | High Mosaic expression rate (40-80%) | 18.9 percentage of embryos | Standard Deviation 30.5 |
p-value: 0.54Wilcoxon signed-rank testing
p-value: 0.2Wilcoxon signed-rank
Secondary
Embryo Quality
Fraction of freezable quality embryos (6 cells or greater, grades 1-2 for symmetry and fragmentation), (%).
Time frame: 2 weeks from start of IVF treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE Media | Embryo Quality | 45.7 percentage of embryos | Standard Deviation 31.1 |
| GLOBAL Media | Embryo Quality | 45.6 percentage of embryos | Standard Deviation 30.8 |
p-value: 0.89Wilcoxon signed-rank testing