Age does not influence the effect of embryo fragmentation on successful blastocyst development

Wu, Diana; Reynolds, K.A.; Maxwell, Rose; Lindheim, Steven R.; Aubuchon, Mira; Thomas, Michael A.

doi:10.1016/j.fertnstert.2011.05.024

Cited by 12 publications

(16 citation statements)

References 19 publications

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“…Our findings are strengthened by the observation of Wu et al [2011] of a significant negative correlation between the degree of embryo fragmentation and blastocyst formation rate. However, age had no effect on the degree of fragmentation within embryos with appropriate cleavage status, nor did it modify the significant effect of embryo fragmentation on blastocyst formation [Wu et al 2011]. Thus, the total blastocyst formation rate did not decrease significantly with the maternal age.…”

Section: Discussionsupporting

confidence: 63%

“…This observation may result in part from increased abnormal chromatin and mitochondrial genome D-loop loci mutations in oocytes of older women [Li et al 2010]. Our findings are strengthened by the observation of Wu et al [2011] of a significant negative correlation between the degree of embryo fragmentation and blastocyst formation rate. However, age had no effect on the degree of fragmentation within embryos with appropriate cleavage status, nor did it modify the significant effect of embryo fragmentation on blastocyst formation [Wu et al 2011].…”

Section: Discussionsupporting

confidence: 62%

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The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes

Yin

Jiang

et al. 2014

Systems Biology in Reproductive Medicine

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(2015) The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes, Systems Biology in Reproductive Medicine, 61:1, 50-56, DOI: 10.3109/19396368.2014 AbstractThe aim of this study was to evaluate the influence of in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI), fertilization mode embryonic morphology at day 3, and female age on blastocyst development, on the clinical outcomes of pregnancy after blastocyst transfer. A total of 471 cycles were retrospectively investigated. The rates of blastocyst formation and of good blastocyst morphology were higher in IVF than in ICSI cycles but there were no significant differences in the clinical pregnancies or in the miscarriage rates. The rates of formation of blastocyst and of blastocysts with good morphology were significantly higher from good-morphology embryos than from poor-morphology embryos. Nevertheless, 16.9% of the poor-morphology embryos reached the blastocyst stage. The total rates of blastocyst formation, and rates of clinical pregnancy and implantation were statistically similar in the age 535, 35-39, and 439 year groups, although tending to decrease with increasing age. When equal numbers of embryos were transferred on day 3, the rates of clinical pregnancy and implantation after blastocyst transfer were significantly higher in the 535 year age group than in the 35-39 and 439 year age groups, which were not significantly different. The miscarriage rates after embryo or blastocyst transfers were not statistically different in groups of similar age. Therefore, extended embryo culture up to the blastocyst stage could be implemented for women aged younger than 35 years to increase the pregnancy rate. For older women, transfer and vitrification of available embryos at day 3 and extended culture of morphologically poor embryos to the blastocyst stage for cryopreservation may improve the clinical outcome.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 62%

The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes

Yin

Jiang

et al. 2014

Systems Biology in Reproductive Medicine

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“…Another potential factor in the capacity of an IVF embryo to successfully implant is the timing and degree of cellular fragmentation, whereby cytoplasmic bodies pinch off of blastomeres during cytokinesis (Alikani et al 1999;Antczak and Van Blerkom 1999). Distinct from cell death-induced DNA fragmentation (Hardy et al 2001;Xu et al 2001), cellular fragmentation also occurs naturally following in vivo human conceptions (Pereda and Croxatto 1978;Buster et al 1985) and is not associated with maternal age (Wu et al 2011). We previously demonstrated that cellular fragments can contain chromosomal material and that mis-segregated chromosomes are encapsulated into micronuclei during mitotic divisions (Chavez et al 2012), but the parental source of this DNA and whether it originated from blastomeres was unknown.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing of Primate Preimplantation Embryos Reveals Chromosome Elimination Via Cellular Fragmentation and Blastomere Exclusion

Daughtry

Rosenkrantz

Lazar

et al. 2018

Preprint

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A major contributor to in vitro fertilization failure and embryo loss is aneuploidy. Human pre-implantation embryos often sequester mis-segregated chromosomes into micronuclei during mitosis, while undergoing a process called cellular fragmentation. Using live-cell imaging, single-cell/fragment DNA-Sequencing, and confocal analyses, we demonstrate in a large number of rhesus embryos that aneuploidy, micronuclei, and cellular fragmentation dynamics is conserved between primates. We also determined that ~18% of fragmented embryos encapsulate whole or partial chromosomes within cellular fragments, which are either maternal or paternal in origin and undergo DNA damage. Additional findings of reciprocal chromosome segments, uniparental genome segregation, and mixoploidy support the prevalence of chromosome breakage and abnormal cytokinesis. Despite frequent chromosomal errors, we show that embryos can prevent incorporation of fragments and non-dividing blastomeres at the blastocyst stage. We propose that embryos respond to segregation errors by eliminating micronuclei via cellular fragmentation and select against aneuploid blastomeres to overcome chromosome instability.. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/241851 doi: bioRxiv preprint first posted online Jan. 2, 2018; 2The demand for human in vitro fertilization (IVF) increases each year, but success rates as measured by live birth(s) have remained only ~30-35% for decades (cdc.gov/art). One of the leading causes of IVF failure and embryo loss is the presence of unbalanced whole chromosome(s), or aneuploidy. Estimates of aneuploidy in IVF embryos via high-resolution techniques are 50-80%, including those from young, fertile couples and irrespective of stage [1][2][3][4][5][6] . Although difficult to ascertain, a similar efficiency (~30-35%) arises from natural human pregnancies, with up to 70% of spontaneous miscarriages diagnosed as aneuploid [7][8][9][10] . Chromosomal mis-segregation in oocytes during meiosis has long been considered the primary reason for aneuploidy, especially in cases of advanced maternal age. However, recent studies using comprehensive chromosome screening (CCS) of all blastomeres in cleavage-stage human embryos established that mitotic errors occur at an equal or greater frequency than meiotic errors and irrespective of maternal age 1,2,4,6,11,12 . Mitotic chromosome mis-segregation may not only lead to aneuploidy, but can also give rise to a mosaic embryo with different chromosomal copy number amongst cells. While classified as aneuploid, euploid-aneuploid mosaic embryos may still result in the birth of healthy offspring upon transfer, which suggests that corrective mechanisms exist to overcome chromosomal instability (CIN) during pre-implantation development [13][14][15] .Another determining factor for the capacity...

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“…However, fragmentation does not seem to correlate with maternal age (10,11), and fragmentation is not an exclusive determinant of developmental competence, which is also related to the number of blastomeres, cell size, number of nuclei, and symmetry (4,(12)(13)(14). Fragmentation has also been observed in embryos of various species in vivo (15)(16)(17), indicating that it is neither a speciesspecific feature nor an artifact of culture in vitro.…”

mentioning

confidence: 98%

Fragmentation of human cleavage-stage embryos is related to the progression through meiotic and mitotic cell cycles

Stensen

Tanbo

Storeng

et al. 2015

Fertility and Sterility

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Age does not influence the effect of embryo fragmentation on successful blastocyst development

Cited by 12 publications

References 19 publications

The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes

The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes

Single-Cell Sequencing of Primate Preimplantation Embryos Reveals Chromosome Elimination Via Cellular Fragmentation and Blastomere Exclusion

Fragmentation of human cleavage-stage embryos is related to the progression through meiotic and mitotic cell cycles

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