Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy.

Objective: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy.

Design: Analysis of data collected between 2017 and 2023.

Setting: Multicenter.

Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism.

The health risks associated with transferring embryos classified as mosaic by preimplantation genetic testing for aneuploidies (PGT-A) are currently unknown. Such embryos produce PGT-A results indicating the presence of both euploid and aneuploid cells and have historically been deselected from transfer and grouped with uniformly aneuploid embryos as 'abnormal'. In recent years, numerous groups have reported the intentional transfer of mosaic embryos in the absence of uniformly euploid embryos, largely observing births of seemingly healthy babies.

SARS-CoV-2 can infect human embryos.

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known.

Haplotype-aware inference of human chromosome abnormalities.

Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies affect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing for aneuploidy (PGT-A).

Let the data do the talking: the need to consider mosaicism during embryo selection.

Chromosomal mosaicism, the coexistence of cells with different chromosomal content, has been documented in human embryos for 3 decades. Early versions of preimplantation genetic testing for aneuploidy (PGT-A) did not measure mosaicism, either because typically only a single cell was assessed or because the technique could not accurately identify it. Although this led to a straightforward diagnosis (an embryo was considered either normal or abnormal), it simply avoided the issue and, in hindsight, may have led to numerous misdiagnoses with negative clinical consequences.

Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use.

Objective: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer.

Design: Compiled analysis.

Setting: Multi-center.

Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements.

There is a high incidence of chromosomal abnormalities in early human embryos, whether they are generated by natural conception or by assisted reproductive technologies (ART). Cells with chromosomal copy number deviations or chromosome structural rearrangements can compromise the viability of embryos; much of the naturally low human fecundity as well as low success rates of ART can be ascribed to these cytogenetic defects. Chromosomal anomalies are also responsible for a large proportion of miscarriages and congenital disorders.

Estimating Demand for Germline Genome Editing: An Fertilization Clinic Perspective.

Germline genome editing (GGE) holds the potential to mitigate or even eliminate human heritable genetic disease, but also carries genuine risks if not appropriately regulated and performed. It also raises fears in some quarters of apocalyptic scenarios of designer babies that could radically change human reproduction. Clinical need and the availability of alternatives are key considerations in the ensuing ethical debate.

Births from embryos with highly elevated levels of mitochondrial DNA.

Research Question: Conflicting data exist on the utility of quantification of mitochondrial DNA (mtDNA) levels as a predictor of blastocyst implantation in the IVF clinic. The current study determined whether blastocysts with highly elevated mtDNA levels could result in healthy pregnancies and births, and whether mitochondrial functional output might be a readout of cell stress in the embryo.

Design: mtDNA levels were determined in 109 blastocysts used in clinical transfers into 100 women, noting their clinical outcomes.

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

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.

Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst.

Study Question: Is a clinical trophectoderm (TE) biopsy a suitable predictor of chromosomal aneuploidy in blastocysts?

Summary Answer: In the analyzed group of blastocysts, a clinical TE biopsy was an excellent representative of blastocyst karyotype in cases of whole chromosome aneuploidy, but in cases of only segmental (sub-chromosomal) aneuploidy, a TE biopsy was a poor representative of blastocyst karyotype.

What Is Known Already: Due to the phenomenon of chromosomal mosaicism, concern has been expressed about the possibility of discarding blastocysts classified as aneuploid by preimplantation genetic testing for aneuploidy (PGT-A) that in fact contain a euploid inner cell mass (ICM). Previously published studies investigating karyotype concordance between TE and ICM have examined small sample sizes and/or have utilized chromosomal analysis technologies superseded by Next Generation Sequencing (NGS).

Is mitochondrial DNA quantitation in blastocyst trophectoderm cells predictive of developmental competence and outcome in clinical IVF?

Behind every successful IVF embryo transfer, there is a great game of chance. Methods seeking to tilt the balance and increase the likelihood of implantation have been proposed and implemented with varying results, including embryo morphology, FISH-PGS, comprehensive chromosomal screening (CCS), morphokinetics, endometrial receptivity testing. It has been suggested that mitochondrial DNA (mtDNA) copy number could serve as a biomarker for embryo viability, but this concept was recently challenged.

Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential.

Objective: To accurately determine mitochondrial DNA (mtDNA) levels in human blastocysts.

Design: Retrospective analysis.

Setting: IVF clinic.