Segmental mosaic embryos, PGT-M recombination and Day 5 vs Day 6 blastocysts

IVF.net Newsdesk

03 October 2026

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Three recent papers in the journals of the American Society for Reproductive Medicine (ASRM) bear directly on embryo testing and selection, from segmental mosaic embryos to Day 6 blastocysts. ASRM highlighted all three in its October round-up. ASRM

Segmental aneuploidy is often mosaic, and often paternal. Al Hashimi and colleagues, with Darren Griffin as senior author, re-examined 105 blastocysts from 86 couples. All had been flagged with a segmental abnormality at preimplantation genetic testing for aneuploidy (PGT-A) (Fertility and Sterility, September 2026). Each embryo was analysed in three samples: the original trophectoderm biopsy, a second trophectoderm biopsy and the inner cell mass. Although the original biopsy called all of them non-mosaic, 81% (85 of 105) gave discordant results across the three samples, consistent with mosaicism. Only 19% were concordant. Errors of paternal origin were found in 49.5% of embryos (52 of 105), and of maternal origin in 38% (40 of 105), and more than half showed evidence of meiotic origin. Multi-sample analysis changed the inferred chromosomal status of 37.1% of the flagged embryos. Al Hashimi et al., 2026

A case of meiotic recombination seen through PGT-M. Iversen and colleagues report a woman carrying pathogenic variants for two X-linked conditions on the same X chromosome (F&S Reports, August 2026). The conditions are ornithine transcarbamylase (OTC) deficiency and steroid sulfatase (STS) deficiency. With preimplantation genetic testing for monogenic conditions (PGT-M), 9 of 13 embryos (69%) inherited both variants or neither, as expected. The other 4 (31%) carried only one, suggestive of meiotic recombination between the two genes, which lie about 31 Mb apart. She transferred a euploid female embryo at low risk for both variants and delivered a healthy term girl; she declined prenatal diagnostic testing. The authors warn that recombination "may lead to unanticipated results when using PGT-M to screen embryos for multiple monogenic conditions" on the same chromosome. Iversen et al., 2026

Day 5 and Day 6 blastocysts differ only subtly. Ortega-Jaén, Capalbo, De los Santos and colleagues sequenced RNA from the mural trophectoderm of 21 blastocysts from 16 couples. Thirteen reached the blastocyst stage on Day 5 and eight on Day 6 (F&S Science, July 2026). They found 111 differentially expressed genes, with Day 5 embryos enriched for translation, metabolism and cell adhesion pathways. The overall gene expression profiles largely overlapped, and the authors read the differences as developmental timing rather than distinct functional states. Ortega-Jaén et al., 2026

For laboratories, a single biopsy call of a segmental abnormality is a weak basis on its own for deciding an embryo's fate. These results should inform how segmental findings are reported, counselled and handled in the lab's embryo disposition policy. Testing for two conditions on the same chromosome needs test design and genetic counselling that plan for recombination. The Day 5 and Day 6 study is small and measured gene expression only, not clinical outcomes, so it should not change transfer policy on its own.

Mª José De los Santos also speaks at the next International IVF Initiative session, Beyond the Bench, on 13 October.