One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies

Chromosomal mosaicism in embryos can exist in a variety of forms, and different characteristics determine the clinical outcome of mosaic embryo transfers.

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Volume 111, Issue 2, Pages 280–293

Authors:

Andrea R. Victor, M.S., Jack C. Tyndall, B.A., Alan J. Brake, M.S., Laura T. Lepkowsky, B.S., Alex E. Murphy, B.S., Darren K. Griffin, Ph.D., D.Sc., Rajiv C. McCoy, Ph.D., Frank L. Barnes, Ph.D., Christo G. Zouves, M.D., Manuel Viotti, Ph.D.

Abstract:

Objective

To investigate the parameters of mosaicism and the biological mechanisms leading to healthy pregnancies from mosaic embryo transfers.

Design

Prospective study.

Setting

IVF center and associated research laboratory.

Patient(s)

Fifty-nine patients.

Intervention(s)

Embryos underwent blastocyst-stage preimplantation genetic testing for aneuploidy by next-generation sequencing. Trophectoderm biopsies containing 20%–80% abnormal cells were deemed mosaic, and corresponding blastocysts were transferred. Mosaic embryos donated to research were examined for karyotype concordance in multiple biopsies and assessed for cell proliferation and death by immunofluorescence and computational quantitation.

Main Outcome Measure(s)

Chemical start of pregnancy, implantation, fetal heartbeat, and birth.

Result(s)

Globally, mosaic embryos showed inferior clinical outcomes compared with euploid embryos. Aneuploid cell percentage in trophectoderm biopsies did not correlate with outcomes, but type of mosaicism did, as embryos with single mosaic segmental aneuploidies fared better than all other types. Mosaic blastocysts generated from oocytes retrieved at young maternal ages (≤34 years) showed better outcomes than those retrieved at older maternal ages. Mosaic embryos displayed low rates of karyotype concordance between multiple biopsies and showed significant elevation of cell proliferation and death compared with euploid embryos.

Conclusion(s)

After euploid embryos, mosaic embryos can be considered for transfer, prioritizing those of the single segmental mosaic type. If a patient has mosaic embryos available that were generated at different ages, preference should be given to those made at younger ages. Intrablastocyst karyotype discordance and differential cell proliferation and death might be reasons that embryos classified as mosaic can result in healthy pregnancies and babies.


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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.

3 Comments

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Amber Gamma 5 months ago

Very excited to see this data published; however I would like to note that NIPT is not the most appropriate follow-up test for women who become pregnant from a mosaic embryo and found its inclusion in the data as proof of a good/"normal" outcome puzzling. Firstly, NIPT is a screening test that uses cell-free fetal DNA, which is placental in origin and therefore arises from the trophectoderm of the embryo. While concordant with the fetus in most cases, it may be normal in the presence of a chromosomally abnormal fetus and is particularly problematic if confined placental mosaicism exists. Second, most NIPT platforms include only chromosomes 13, 18, 21 and the sex chromosomes and therefore give you no information on other chromosome aneuploidies that may have been mosaic in the embryo on PGT-A. Finally, while a whole-genome NIPT is currently available, there remain a lot of unknowns about the performance of this screening test in terms of its positive predictive value (PPV) and negative predictive values (NPV). False-positives are likely on this testing, which would push a patient with a very precious pregnancy to diagnostic testing through CVS or amniocentesis. Amniocentesis remains the optimal follow-up test for patients who become pregnant (with 50 cell karyotype and microarray if a segmental mosaic was transferred!). NIPT must be offered with care and proper counseling regarding the limitations. Thanks for this exciting paper!

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Antonio Alcaide about 1 month ago

Dear Dr. Victor, congratulations for your work here. I couldn't approach you during the last PGDIS meeting so, if I may, I ask you now… have you studied the DNA content of the segment involved prior to the transfer of  segmental mosaic embryos?, do you consider necessary to explore the CNV region for an accurate genetic counselling before considering the embryo for transfer?.

Thank you

Antonio Alcaide, M. Sc. ASSACELL Biologists, Spain.

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Marine Poulain about 1 month ago

Thank you for this great paper. Among mosaic embryos transferred, you describe better outcomes in young patients. Do you notice additional morphological disparities such as more late blastocyst obtained on day6 for these mosaic embryos in older patients?