Preferential selection and transfer of euploid noncarrier embryos in preimplantation genetic diagnosis cycles for reciprocal translocations

A novel strategy involving mate pair sequencing to identify reciprocal translocation breakpoints enables patients to undertake a clinical preimplantation genetic diagnosis cycle and select euploid noncarrier embryos for preferential transfer.

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Volume 108, Issue 4, Pages 620–627.e4

Authors:

Li Wang, M.D., Ph.D., Jiandong Shen, M.D., David S. Cram, Ph.D., Minyue Ma, Ph.D., Hui Wang, M.D., Wenke Zhang, Ph.D., Junmei Fan, Ph.D., Zhiying Gao, M.D., Liwen Zhang, M.D., Zhifeng Li, Ph.D., Mengnan Xu, B.Sc., Don A. Leigh, Ph.D., Alan O. Trounson, Ph.D., Jiayin Liu, M.D., Ph.D., Yuanqing Yao, M.D., Ph.D.

Abstract:

Objective

To develop and validate a new strategy to distinguish between balanced/euploid carrier and noncarrier embryos in preimplantation genetic diagnosis (PGD) cycles for reciprocal translocations and to successfully achieve a live birth after selective transfer of a noncarrier embryo.

Design

Retrospective and prospective study.

Setting

In vitro fertilization (IVF) units.

Patient(s)

Eleven patients undergoing mate pair sequencing for identification of translocation breakpoints, followed by clinical PGD cycles.

Intervention(s)

Embryo biopsy with 24-chromosome testing to determine carrier status of balanced/euploid embryos.

Main Outcome Measure(s)

Definition of translocation breakpoints and polymerase chain reaction (PCR) diagnostic primers, correct diagnosis of euploid embryos for carrier status, and a live birth with a normal karyotype after transfer of a noncarrier embryo.

Result(s)

In 9 of 11 patients (82%), translocation breakpoints were successfully identified. In four patients with a term PGD pregnancy established with a balanced/euploid embryo of unknown carrier status, the correct carrier status was retrospectively determined, matching with the cytogenetic karyotype of the resulting newborns. In a prospective PGD cycle undertaken by a patient with a 46,XY,t(7;14)(q22;q24.3) translocation, the four balanced/euploid embryos identified comprised three carriers and one noncarrier. Transfer of the noncarrier embryo resulted in birth of a healthy girl who was subsequently confirmed with a normal 46,XX karyotype.

Conclusion(s)

The combination of mate pair sequencing and PCR breakpoint analysis of balanced reciprocal translocation derivatives is a novel, reliable, and accurate strategy for distinguishing between carrier and noncarrier balanced/euploid embryos. The method has potential application in clinical PGD cycles for patients with reciprocal translocations or other structural rearrangements.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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