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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how often embryos labeled as abnormal in genetic testing can still lead to healthy babies. It also examines whether pregnancies from these embryos have more complications or result in health issues for the child within the first five years. The trial compares two groups: one where embryos with known genetic issues are transferred (non-euploid embryo transfer) and another where only embryos without known issues are used (euploid embryo transfer). Prospective participants may be a good fit if they wish to become pregnant, have embryos with genetic abnormalities available, and can travel to Stanford for treatment. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could redefine genetic testing standards in fertility treatments.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transferring embryos that are not fully normal (non-euploid) is generally safe, though they may have a lower chance of leading to pregnancy. Some studies indicate that embryos with a mix of normal and abnormal cells (mosaicism) are less likely to result in pregnancy compared to completely normal embryos.

While safety data collection continues, current evidence suggests that these embryos can lead to successful pregnancies, albeit with a slightly lower success rate. No significant increase in negative outcomes has been observed, indicating that the process is generally well-tolerated. However, it is important to understand that these embryos might behave differently than typical ones, and ongoing research aims to fully understand these differences. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard approach of only transferring euploid embryos during in vitro fertilization (IVF), the treatment under study explores the potential of transferring non-euploid embryos, which are typically not considered viable due to abnormalities. Researchers are excited about this approach because it broadens the potential for achieving pregnancy when no euploid embryos are available. Non-euploid embryos include aneuploid and mosaic embryos, which might still result in successful pregnancies in certain cases. This trial may offer new hope for patients with limited embryo options, potentially increasing the chances of pregnancy for those who would otherwise have no viable embryos to transfer.

What evidence suggests that this trial's treatments could be effective?

This trial will compare the outcomes of transferring non-euploid embryos with euploid embryos. Research has shown that transferring embryos with abnormalities, known as non-euploid embryos, can still lead to successful pregnancies. Studies indicate that embryos with a mix of normal and abnormal cells, called mosaic embryos, have a lower chance of resulting in a pregnancy compared to normal embryos. Specifically, mosaic embryos have about a 40.6% chance of leading to a pregnancy. However, some research suggests that mosaic embryos can sometimes achieve outcomes similar to normal embryos. Additionally, transferring non-euploid embryos generally results in lower rates of implantation and live births compared to normal embryos. Despite these challenges, successful pregnancies with non-euploid embryos remain possible. ^{2 3 4 6 7}

Who Is on the Research Team?

Ruth Lathi, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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 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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7565393/

The Pregnancy Outcome of Mosaic Embryo Transfer Moreover, embryos with mosaicism had a statistically lower chance of reaching clinical pregnancy in the MET group (CPR 40.6%, 54/133) than in ...

2. withpower.com withpower.com/trial/phase-aneuploidy-3-2019-c05b8

Non-euploid Embryo Transfer for Aneuploidy and Mosaicism Trial Overview The study is testing the outcomes of transferring non-euploid (abnormal) embryos into participants compared to normal (euploid) embryo transfers.

3. asrm.org asrm.org/practice-guidance/practice-committee-documents/clinical-management-of-mosaic-results-from-preimplantation-genetic-testing-for-aneuploidy-pgt-a-of-blastocysts-a-committee-opinion/

Clinical management of mosaic results from ... Current prospective MET data indicate reduced pregnancy potential of embryos reported as mosaic for 3 or more chromosomes as compared with those with one or 2 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1472648322000682

Neonatal and clinical outcomes after transfer of a mosaic ... Overall, EET resulted in a significantly higher implantation rate (47.0%) and LBR (40.7%) than MET (implantation rate 39.0%, P = 0.005; LBR 28.8%, P = 0.008) ...

5. cell.com cell.com/ajhg/fulltext/S0002-9297(21)00412-2

Mosaic human preimplantation embryos and their ... We report that putative mosaic embryos show clinical outcomes similar to those of uniformly euploid embryos and that there are not any ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07036536

Non-Euploid Embryo Transfer (NEET) Registry This study aims to collect prenatal, neonatal and pediatric outcome information for embryos transferred with the various types of non-euploid PGT-A results.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8609000/

Evidence-based clinical prioritization of embryos with mosaic ... The purpose of this review and meta-analysis is to standardize the practice of mosaic embryo transfer, based on the current available evidence.