Preimplantation Genetic Testing �for HLA Matching: �Clinical Applications and Ethical Considerations

Andria Besser, MS, CGC

Emily Patterson, BS

NYU Langone Fertility Center

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February 4, 2026

Disclosures

The speakers do not have anything to disclose.

Learning Objectives

1. Describe PGT for HLA matching, including laboratory methodologies and clinical challenges

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• Evaluate ethical considerations unique to PGT for HLA matching

Preimplantation Genetic Testing

• Process by which embryos created through IVF undergo genetic testing
• Purpose/goal varies depending on test target

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PGT is current terminology as of 2017 (replaces PGD/PGS)

• Types of PGT
• PGT-A (Aneuploidy)
• PGT-SR (Structural Rearrangement)
• PGT-M (Monogenic)
• PGT-HLA

PGT for HLA Matching

• Selection of embryos that are HLA compatible (identical) to a sibling in need of a stem cell transplant

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• Can be done alone or in conjunction with PGT-M for underlying condition

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• HLA = Human Leukocyte Antigen
• 3-4 Mb complex of genes that regulate immune function (major histocompatibility complex)
• Transplant has best prognosis if HLA genotype is identical between donor and recipient
• Full genetic siblings have 25% chance of exact match

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PGT-M for HLA matching

1^st PGT-HLA baby born Aug 2000

Trends in PGT for HLA Matching

• Same lab: 14 more matched babies born by 2004 (Kuliev et al), 45 by 2009, 569 by 2023 (Rechitsky, PGDIS)
• ESHRE study (Kakourou et al, 2018)
• 14 IVF centers between 2001-2015
• 364 couples underwent 704 cycles (70% at a single clinic in Türkiye)
• 94% had no known infertility; average maternal age 33.5
• 42 different indications; 81% also tested for a condition (beta-thalassemia most common)
• 136 babies born to 113 couples (19.3% LBR per start; 2.5% per embryo tested)
• Transplant reported for 57 cases; 77% uncomplicated

Trends in PGT for HLA Matching

NYU internal data, 2025

12 pts (27 cycles) since 2002

• 5 pts HLA only
• 7 with a gene

IVF with PGT-M/HLA process

Custom test development

Controlled ovarian

hyperstimulation & oocyte retrieval

Fertilization/ICSI (intracytoplasmic sperm injection)

Embryo culture to blastocyst stage

Trophectoderm biopsy & embryo cryopreservation

Embryo warming & transfer into uterus

Genetic testing of biopsied cells

1

2

3

4

5

6

7

Linkage-Based Testing

HLA haplotyping using STRs or SNPs throughout and flanking the HLA region

MATCH

ABCD

5678

QRST

EFGH

5678

EFGH

1 in 4 (25%) chance for each embryo to be a full match

MATCH

Half-match

Half-match

Non-match

Limitations and Considerations

1. Recombination
2. Linked genes
3. Accuracy
4. Odds of success

~5% of HLA alleles are recombinant

ABCD

5678

QRST

EFGH

5678

EFGH

78

Limitations and Considerations

1. Recombination
2. Linked genes
3. Accuracy
4. Odds of success

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… a match could only occur if recombination happens in the same spot

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This situation may not be identified until the embryos are tested

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If the affected child is recombinant…

ABCD

5678

QRST

EFGH

EFGH

ABCD

78

Limitations and Considerations

1. Recombination
2. Linked genes
3. Accuracy
4. Odds of success

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• FANCE gene is located at 6p21.3 in close proximity to HLA region (~2 Mb apart)
• If trying to match to a FANCE-affected child, most HLA matches are expected to also be FANCE-affected

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Limitations and Considerations

1. Recombination
2. Linked genes
3. Accuracy
4. Odds of success

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• PGT accuracy is limited by the small amount of DNA that can be obtained from a single trophectoderm biopsy
• Lack of informative markers may further reduce accuracy
• Sources of misdiagnosis include:
• Allele dropout / failed amplification
• Undetected recombination
• Contamination (external, parental tissue)
• Prenatal/postnatal confirmation of HLA genotype is still necessary

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Limitations and Considerations

1. Recombination
2. Linked genes
3. Accuracy
4. Odds of success

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1/4 chance of HLA match

3/4 chance to be unaffected

3/32 chance of unaffected euploid match

(~9% per embryo)

1/2 chance to be euploid

For a <35 pt testing for HLA + AR condition…

Euploid embryos have ~50% chance of live birth

A familiar example of PGT-HLA

• Anna conceived through PGT-HLA as savior sibling for Kate
• At 13, parents decide Anna must donate her kidney against her dissent
• Anna sues for medical emancipation
• Major themes:

Parental motivations in pursuing PGT-HLA

• Dual motive: expand the family with a biologically related child while potentially providing life-saving care option for sick sibling
• Procreative beneficence
• Moral defensibility generally rests on parental intent to love & care for the new child regardless of the transplant outcome

Concerns: Instrumentalization of the donor child

• Kantian objection: treating donor child as means to an end
• “Spare parts” argument
• Dual-motive defense
• Conditional existence
• But does this constitute harm?
• Non-Identity Problem (NIP)

Best interests of the children

• Interest in intact family structure may be assumed for donor child
• Does PGT-HLA undermine donor child’s interest in self-determination?
• Parents experience a conflict of best interests between children
• Weigh the magnitude of potential harms

Concerns: Potential risks incurred by the future child

• Physical harms
• Umbilical cord blood transplant
• Subsequent HSCTs from bone marrow
• Solid organ donation
• Psychological trauma for both children
• "Gift of life" & failure burdens

Considerations towards viable non-matches

• Is aggregate disposition an instrumental use of embryo creation?
• What do PGT-HLA utilization trends tell us?
• NYU data: 5/12 patients transferred non-matches

Stance of Professional Organizations

• ASRM (2023): Non-directive, clinicians may offer PGT-HLA
• Not recommended for conditions where HSCT is not standard of care
• ESHRE (2020): PGT-HLA is acceptable when all other clinical options are exhausted & HSCT is expected to cure or extend life
• Opposes PGT-HLA in the absence of a specific disease

Case: “Preventative” PGT-HLA

• Couple presented for IVF due to partner leukemia in 6/2011
• Planned for ≥ 2 children (healthy 2 y/o son)
• Male partner passed 12/2011, had banked sperm for pt. use
• DS/DE or adoption if sperm failed
• Pursued PGT-HLA “off-label” in 7/2012 using partner’s sperm
• 1 euploid match, 2 euploid non-matches
• Outcome: 1 LB, HLA-matched daughter

What do we think?

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• Parent motivations
• Weighing potential harms
• Appropriateness

References

Attia, M., Kripalani, S., Darbari, I., & Nickel, R. S. (2020). Parents of children with sickle cell disease are interested in preimplantation genetic testing. The Journal of Pediatrics, 223, 178–182.

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BBC. (2000, October 4). Baby created to save older sister. BBC News. http://news.bbc.co.uk/2/hi/health/954408.stm

Carvalho, F., Coonen, E., Goossens, V., Kokkali, G., Rubio, C., Meijer-Hoogeveen, M., Moutou, C., Vermeulen, N., & De Rycke, M. (2020). ESHRE PGT Consortium good practice recommendations for the organisation of PGT. Human Reproduction Open, 2020(3), hoaa021.

Chambers, K. L. (2025). A Non-Solution to the Non-Identity Problem. Ethical Theory and Moral Practice, 1-14.

Hughes, T., Bracewell-Milnes, T., Saso, S., Jones, B. P., Almeida, P. A., Maclaren, K., Norman-Taylor, J., Johnson, M., & Nikolaou, D. (2021). A review on the motivations, decision-making factors, attitudes and experiences of couples using preimplantation genetic testing for inherited conditions. Human Reproduction Update, 27(5), 944–970.

Kakourou G, Kahraman S, Ekmekci GC, Tac HA, Kourlaba G, Kourkouni E, Sanz AC, Martin J, Malmgren H, Giménez C, Gold V, Carvalho F, Billi C, Chow JFC, Vendrell X, Kokkali G, Liss J, Steffann J, Traeger-Synodinos J. The clinical utility of PGD with HLA matching: a collaborative multi-centre ESHRE study. Hum Reprod. 2018 Mar 1;33(3):520-530.

Kuliev A, Verlinsky Y. Preimplantation HLA typing and stem cell transplantation: report of International Meeting, Cyprus, 27-8 March, 2004. Reprod Biomed Online. 2004 Aug;9(2):205-9.

Kunacheewa, C., Ungprasert, P., Phikulsod, P., Issaragrisil, S., & Owattanapanich, W. (2020). Comparative efficacy and clinical outcomes of haploidentical stem cell transplantation to other stem sources for treatment in acute myeloid leukemia and myelodysplastic syndrome patients: a systematic review and meta-analysis. Cell transplantation, 29, 0963689720904965.

Lai, A. T. Y. (2011). To be or not to be my sister’s keeper? A revised legal framework safeguarding savior siblings’ welfare. The Journal of Legal Medicine, 32(3), 261–293.

Pennings, G., Schots, R., & Liebaers, I. (2002). Ethical considerations on preimplantation genetic diagnosis for HLA typing to match a future child as a donor of haematopoietic stem cells to a sibling. Human Reproduction, 17(3), 534–538.

Picoult, J. (2009). My Sister's Keeper: A Novel. Simon and Schuster.

Practice Committee and Genetic Counseling Professional Group of the American Society for Reproductive Medicine. (2023). Indications and management of preimplantation genetic testing for monogenic conditions: A committee opinion. Fertility and Sterility, 120(1), 61–71.

Thank you!