Non-euploid Embryo Transfer for Aneuploidy and Mosaicism

(TAME Trial)

Overseen By REI Research Coordinator

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: International donor eggs, Living outside US, Triploidy embryos

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Non-euploid Embryo Transfer for Aneuploidy and Mosaicism?

Research indicates that mosaic embryos, which have a mix of normal and abnormal cells, can still lead to successful pregnancies and healthy births, especially if less than 50% of the cells are abnormal. This suggests that transferring mosaic embryos can be a viable option when euploid embryos (those with the correct number of chromosomes) are not available. ^{1 2 3 4 5}

Is transferring non-euploid or mosaic embryos generally safe for humans?

Transferring mosaic embryos can lead to healthy births, but it is associated with a higher risk of miscarriage and potential genetic abnormalities compared to transferring normal embryos. Some cases have shown that mosaicism can persist during pregnancy, leading to severe health issues, so careful genetic counseling and testing are recommended before proceeding. ^{1 4 6 7 8}

How does the Non-euploid Embryo Transfer treatment differ from other treatments for aneuploidy and mosaicism?

The Non-euploid Embryo Transfer treatment is unique because it involves transferring embryos that are not perfectly chromosomally normal (non-euploid), including those with mosaicism (a mix of normal and abnormal cells), which is different from the standard practice of only transferring euploid (normal) embryos. This approach may offer more options for patients who have limited or no euploid embryos available for transfer. ^{9 10 11 12 13}

What is the purpose of this trial?

This trial uses genetic testing on embryos before they are implanted in the womb to check for abnormalities. It focuses on patients undergoing procedures with embryos that have been flagged as abnormal. The goal is to see if these embryos can still lead to healthy babies and to monitor any risks over time.

Research Team

Ruth Lathi, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals who can travel to Stanford, speak English fluently, and have aneuploid or mosaic embryos ready for transfer but no healthy euploid embryos available. It's not open to those using a gestational carrier, living outside the U.S., or with embryos diagnosed with Trisomy 18, Trisomy 13, or Triploidy.

Inclusion Criteria

I do not have any healthy embryos for use.

I have embryos that are not typical in their chromosome number.

Willing to travel to Stanford for treatment

Exclusion Criteria

You do not live in the United States.

My embryos do not have Trisomy 18, Trisomy 13, or Triploidy.

You are using a surrogate mother to carry your child.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Embryo Transfer

Participants undergo embryo transfer of either non-euploid or euploid embryos

3 years

Multiple visits for embryo transfer and monitoring

Pregnancy Monitoring

Pregnancy outcomes and any complications are recorded

4 years

Regular visits for pregnancy monitoring

Pediatric Follow-up

Pediatric development is monitored up to 5 years after birth

7 years 3 months

Periodic visits for developmental assessments

Treatment Details

Interventions

• Euploid Transfer
• Non-euploid embryo transfer

Trial Overview The study is testing the outcomes of transferring non-euploid (abnormal) embryos into participants compared to normal (euploid) embryo transfers. The focus is on live birth rates and any health or developmental issues in children up to five years post-birth.

Participant Groups

Group I: Non-euploid Transfer Experimental Treatment 1 Intervention

Patients desiring pregnancy who have no acceptable euploid embryos available for transfer who chose to undergo embryo transfer of a non-euploid embryo (either aneuploid or mosaic).

Group II: Euploid Transfer Active Control 1 Intervention

Patients desiring pregnancy who are undergoing euploid embryo transfer

Euploid Transfer is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Approved in United States as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Approved in Canada as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Approved in Japan as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Approved in China as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Approved in Switzerland as Euploid Embryo Transfer for:

• Infertility treatment
• IVF

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

Euploid embryo transfers (EET) resulted in significantly higher implantation rates (47.0%) and live birth rates (40.7%) compared to mosaic embryo transfers (MET), which had rates of 39.0% and 28.8%, respectively, indicating that euploid embryos are more effective for achieving successful pregnancies.

Segmental mosaic embryos showed comparable implantation and live birth rates to euploid embryos, while those with a high percentage of aneuploid cells (≥60%) had a significantly lower live birth rate (10.5%), suggesting that such embryos should be prioritized lower for transfer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal and clinical outcomes after transfer of a mosaic embryo identified by preimplantation genetic testing for aneuploidies. Yakovlev, P., Vyatkina, S., Polyakov, A., et al.[2022]

In a study of 113 blastocysts from 58 IVF cycles, it was found that higher quality trophectoderm morphology (grades A and B) was associated with higher rates of euploidy, with rates of 71.43% and 60%, respectively.

Despite the correlation between trophectoderm quality and euploidy, the study concluded that morphology alone cannot guarantee genetic viability, highlighting the need for genetic analysis to confirm embryo quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can trophectoderm morphology act as a predictor for euploidy? Yoshida, IH., Santos, M., Berton, CZ., et al.[2019]

Embryos with segmental mosaicism have a significantly lower live-birth rate (30.0%) compared to euploid embryos (53.8%), indicating reduced reproductive potential.

The transfer of segmental mosaic embryos is associated with a higher spontaneous abortion rate (40.0%) compared to euploid controls (18.2%), suggesting that segmental mosaicism negatively impacts pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate. Zore, T., Kroener, LL., Wang, C., et al.[2019]

Embryonic mosaicism, where embryos contain cells with different genetic makeups, can complicate preimplantation genetic screening (PGS) results, and while some mosaic embryos can lead to live births, they generally have lower implantation and pregnancy success rates.

It is recommended to prioritize the transfer of euploid embryos over mosaic ones due to the increased risks of genetic abnormalities and adverse outcomes associated with certain types of mosaic embryos, particularly those with trisomies 2, 7, 13, 14, 15, 16, 18, and 21.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and clinical management of embryonic mosaicism. Sachdev, NM., Maxwell, SM., Besser, AG., et al.[2017]

Mosaic embryos, particularly those with less than 50% aneuploidy, have shown reproductive potential, yielding live birth rates comparable to euploid embryos, which is significant given the increasing identification of these embryos due to improved diagnostic techniques.

The review emphasizes the need for proper guidelines to select suitable mosaic embryos for transfer, aiming to reduce embryo wastage and enhance the success rates of embryo transfers in assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preimplantation genetic testing for aneuploidy: The management of mosaic embryos. Yu, EJ., Kim, MJ., Park, EA., et al.[2022]

Mosaic embryo transfers (METs) resulted in significantly lower clinical pregnancy rates (40.1%) and ongoing/live birth rates (27.1%) compared to euploid (59.0% and 47.0%) and non-PGT embryos (48.4% and 35.1%), indicating reduced efficacy of METs in achieving successful pregnancies.

Despite the lower success rates, all 37 live births from METs were confirmed viable, and prenatal genetic testing showed normal results in 8 cases, supporting the potential for healthy outcomes despite the initial chromosomal mosaicism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis. Zhang, YX., Chen, JJ., Nabu, S., et al.[2023]

Two cases of pregnancies resulting from the transfer of mosaic embryos revealed that chromosomal abnormalities persisted from the embryonic stage into the pregnancy, leading to severe health issues.

These cases highlight the potential risks associated with transferring mosaic embryos, suggesting that careful risk-benefit assessments are necessary before proceeding with such transfers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism. Greco, E., Yakovlev, P., Kornilov, N., et al.[2023]

In a study involving 70 patients who underwent IVF, transferring mosaic embryos resulted in implantation and pregnancy outcomes that were only slightly different from those achieved with fully normal embryos.

The study emphasizes the importance of accurately interpreting mosaic embryo results and suggests that proper patient counseling and prenatal testing are essential for managing potential risks associated with these embryos.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes after transfers of embryos with chromosomal mosaicism: a single reproductive medicine center experience at iVF Riga clinic. Alksere, B., Grinfelde, I., Kornejeva, L., et al.[2021]

In a study of 26 pediatric patients with non-malignant diseases who underwent haploidentical stem cell transplantation (haplo-HSCT), the 1-year cumulative incidence of graft failure was 27.4%, indicating a significant risk of transplant complications.

The 2-year overall survival rate for patients with primary immunodeficiency disorders was 44.9%, and the transplantation-related mortality at day 100 was 30.8%, highlighting the need for improved procedures and centralization in specialized centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH). Torres Canizales, J., Ferreras, C., Pascual, A., et al.[2021]

Haploidentical stem cell transplantation has become a viable option for about 50% of patients with hematological malignancies lacking matched donors, with advancements in graft processing ensuring effective outcomes.

Current graft processing methods achieve over 90% engraftment rates while significantly reducing the risks of severe acute graft-versus-host disease (GvHD) and Epstein-Barr virus-related complications, thanks to optimized selection techniques that meet essential requirements for stem cell quantity and T/B cell depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft engineering for allogeneic haploidentical stem cell transplantation. Tabilio, A., Falzetti, F., Zei, T., et al.[2006]

Haploidentical stem cell transplantation offers immediate donor availability and has shown promising results in reducing graft-versus-host disease (GVHD) rates when combined with high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil.

This approach has achieved engraftment and GVHD rates comparable to those of HLA-matched sibling transplants, indicating that significant challenges in haploidentical transplantation can be addressed, paving the way for further optimization in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in haploidentical stem cell transplantation. Bayraktar, UD., Champlin, RE., Ciurea, SO.[2021]

Haploidentical transplantation offers a viable treatment option for children with otherwise incurable diseases, such as certain cancers and genetic disorders, by using family members as donors, which increases accessibility.

Recent advancements in graft manipulation and supportive care have significantly improved the success rates of haploidentical transplants, making them safer and more effective compared to earlier attempts, while also eliminating the need for matched unrelated donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New strategies for haploidentical transplantation. Oevermann, L., Handgretinger, R.[2012]

Haploidentical stem cell transplantation allows patients without HLA identical donors, particularly in ethnic minority groups, to access potentially life-saving treatment for various diseases.

Recent advancements in in vitro graft manipulation have made haploidentical transplantation safer and more efficient, paving the way for its use in broader cellular immunotherapy applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid immune recovery and low TRM in haploidentical stem cell transplantation in children and adolescence using CD3/CD19-depleted stem cells. Bader, P., Soerensen, J., Jarisch, A., et al.[2017]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Neonatal and clinical outcomes after transfer of a mosaic embryo identified by preimplantation genetic testing for aneuploidies. [2022]

2. Brazil pubmed.ncbi.nlm.nih.gov

Can trophectoderm morphology act as a predictor for euploidy? [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Diagnosis and clinical management of embryonic mosaicism. [2017]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Preimplantation genetic testing for aneuploidy: The management of mosaic embryos. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Pregnancy Outcome of Mosaic Embryo Transfer: A Prospective Multicenter Study and Meta-Analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The outcomes after transfers of embryos with chromosomal mosaicism: a single reproductive medicine center experience at iVF Riga clinic. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH). [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Graft engineering for allogeneic haploidentical stem cell transplantation. [2006]

11. United States pubmed.ncbi.nlm.nih.gov

Progress in haploidentical stem cell transplantation. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

New strategies for haploidentical transplantation. [2012]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Rapid immune recovery and low TRM in haploidentical stem cell transplantation in children and adolescence using CD3/CD19-depleted stem cells. [2017]