Infertility, Oocyte Maturation
Conditions
Keywords
Rescue in vitro maturation, r-IVM, Germinal vesicle oocyte, iPSC-derived ovarian support cells, OSC co-culture, Embryo development, IVF, Sibling-oocyte trial
Brief summary
This single-center randomized sibling-oocyte controlled trial evaluates whether co-culture with induced pluripotent stem cell (iPSC)-derived ovarian support cells (OSCs) improves rescue in vitro maturation (r-IVM) outcomes of surplus germinal vesicle (GV) oocytes collected during routine IVF treatment. Eligible GV oocytes from each enrolled participant are allocated within participant in a 1:1 ratio to either conventional r-IVM or r-IVM with OSC co-culture. The primary outcome is the metaphase II (MII) maturation rate after 24 hours of culture. Secondary outcomes include fertilization rate, day 3 embryo formation, good-quality day 3 embryo rate, blastocyst formation, and good-quality blastocyst rate. All embryos generated in the study are for research purposes only and will not be used for clinical embryo transfer.
Detailed description
Immature human oocytes at the germinal vesicle (GV) stage retrieved during routine IVF cycles are usually not used in standard clinical treatment. Rescue in vitro maturation (r-IVM) offers a potential strategy to increase the number of mature oocytes available for laboratory use, but maturation outcomes for GV oocytes remain limited. This study investigates whether co-culture with iPSC-derived ovarian support cells (OSCs) can improve the biological performance of r-IVM in surplus GV oocytes. This is a single-center, randomized, sibling-oocyte controlled study conducted at the Infertility Department of Hung Vuong Hospital, Ho Chi Minh City, Vietnam. Women undergoing routine IVF who have at least two eligible GV oocytes in one retrieval cycle may participate after providing informed consent. Within each participant, eligible GV oocytes are allocated in a 1:1 ratio to either conventional r-IVM in CSCMC medium or r-IVM in CSCMC medium with iPSC-derived OSC co-culture. Allocation is performed separately within each participant using a manual lottery-based randomization procedure. If an odd number of eligible GV oocytes is available, one oocyte is randomly excluded before allocation to preserve equal within-participant assignment. Oocytes in both groups are cultured under identical laboratory conditions; the only difference between groups is the presence of OSCs in the intervention arm. Matured oocytes are assessed after 24 hours. Oocytes reaching MII undergo ICSI, and fertilized oocytes are cultured to day 5-6 in a time-lapse system. Embryo development is evaluated using standard morphology criteria with independent assessment and time-lapse support. The study is designed to compare biological outcomes between conventional r-IVM and OSC-supported r-IVM while minimizing between-patient confounding through within-participant allocation. The participant is treated as the clustering unit for statistical analysis. This section is taken from the protocol's rationale, procedures, randomization logic, and outcome plan.
Interventions
OTHERConventional rescue in vitro maturation
Standard rescue in vitro maturation of denuded germinal vesicle oocytes in CSCMC culture medium for 24 hours under routine IVF laboratory conditions.
OTHERRescue in vitro maturation with iPSC-derived ovarian support cell co-culture
Rescue in vitro maturation of denuded germinal vesicle oocytes in CSCMC culture medium for 24 hours with co-culture using iPSC-derived ovarian support cells supplied by Dioseve Inc. and prepared according to the laboratory SOP.
Sponsors
Hung Vuong Hospital
Dioseve Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
Embryologists performing culture procedures cannot be blinded because the presence or absence of OSC co-culture is evident during laboratory handling. However, outcome assessment is performed independently by embryologists who are not involved in allocation and who assess recoded masked identifiers.
Intervention model description
Within each enrolled participant, eligible GV oocytes are allocated in a 1:1 ratio to conventional rescue in vitro maturation (r-IVM) or r-IVM with iPSC-derived ovarian support cell (OSC) co-culture. Allocation is performed separately within each participant using a manual lottery-based randomization procedure. When an odd number of eligible GV oocytes is available, one oocyte is randomly excluded before allocation to preserve equal within-participant assignment. The participant is treated as the clustering unit in statistical analyses.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Women aged 18 to 45 years. * At least 2 GV oocytes retrieved in a single oocyte retrieval cycle. * Voluntary informed consent from the couple to participate in the study. * Agreement that all embryos generated from the study will be used for research purposes only and will not be transferred for clinical treatment.
Exclusion criteria
* Sperm obtained through surgical retrieval procedures, including PESA, MESA, TESE, or micro-TESE. * Use of donor gametes, including donor oocytes or donor sperm. * Participants with GV oocytes showing obvious morphological abnormalities, such as degeneration, severe deformation, or marked cytoplasmic abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MII maturation rate after 24 hours of culture | 24 hours after initiation of culture | Proportion of cultured GV oocytes that reach metaphase II (MII) after 24 hours of rescue in vitro maturation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fertilization rate | 17 to 19 hours after ICSI | Proportion of injected oocytes showing normal fertilization with two pronuclei (2PN). |
| Day 3 embryo formation rate | Day 3 after fertilization | Proportion of normally fertilized oocytes that develop to cleavage-stage embryos by day 3. |
| Good-quality day 3 embryo rate | Day 3 after fertilization | Proportion of day 3 embryos meeting predefined good-quality criteria. |
| Blastocyst formation rate | Day 5 to Day 6 after fertilization | Proportion of normally fertilized oocytes that develop to the blastocyst stage by day 5 or day 6. |
| Good-quality blastocyst rate | Day 5 to Day 6 after fertilization | Proportion of blastocysts meeting predefined good-quality criteria. |
Countries
Vietnam
Contacts
CONTACTHuy Phuong Tran, PhD
PRINCIPAL_INVESTIGATORTuyet Thi-Diem Hoang, MD
Hung Vuong Hospital
Outcome results
None listed