Preimplantation Genetic Testing: Where We Are Today

Greco, Ermanno; Litwicka, Katarzyna; Minasi, Maria Giulia; Cursio, Elisabetta; Greco, Pierfrancesco; Barillari, Paolo

doi:10.3390/ijms21124381

Cited by 63 publications

(43 citation statements)

References 191 publications

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“…Some indicate that advanced maternal age was not seen to be correlated with a higher prevalence of mosaicism (Munné and Wells 2017;Nakhuda et al 2018). Other reports observed a significant maternal age effect on the success of mosaic embryos (Victor et al 2019;Greco et al 2020), while Coll et al (2020), found that a positive association with mosaicism showed only paternal age. Our data demonstrate meaningful differences in the maternal age distributions between disease-defined males and females, while paternal ages did not differ.…”

Section: Parental Ages Of Segmental Mosaicism Carriersmentioning

confidence: 97%

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Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Kovaleva¹,

Cotter²

2022

J Appl Genetics

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Mosaicism for unbalanced chromosomal rearrangements segmental mosaicism (SM) is rare, both in patients referred for cytogenetic testing and in prenatal diagnoses. In contrast, in preimplantation embryos SM is a frequent finding and, therefore, is even more challenging. However, there is no consistency among results of published studies on the clinical outcomes of embryos with SM, primarily due to the small number of reported cases. Moreover, there is the problem of predicting the potential for the optimal development of a mosaic embryo to a healthy individual. Therefore, we suggested comparing factors predisposing to favorable and poor prognoses, identified in postnatal and prenatal cohorts of SM carriers, with those obtained from studies on preimplantation embryos. We analyzed 580 published cases of SM including (i) postnatally diagnosed affected carriers, (ii) clinically asymptomatic carriers, (iii) prenatally diagnosed carriers, and (iv) miscarriages. We observed a concordance with preimplantation diagnoses regarding the clinical significance of the extent of mosaicism as well as a predominance of deletions over other types of rearrangements. However, there is no concordance regarding excessive involvement of chromosomes 1, 5, and 9 in unbalanced rearrangements and a preferential involvement of larger chromosomes compared to short ones. Paternal age was not found to be associated with SM in postnatally disease-defined individuals. We have identified maternal age and preferential involvement of chromosome 18 in rearrangements associated with clinical manifestations. Male predominance was found among normal pregnancy outcomes and among disease-defined carriers of rearrangements resulting in a gain of genomic material. Female predominance was found among abnormal pregnancy outcomes, among disease-defined carriers of loss and gain/loss rearrangements, and among transmitting carriers of gonadal SM, both affected and asymptomatic. According to data obtained from “post-embryo” studies, clinical manifestations of chromosomal imbalance are associated with a high proportion of abnormal cells, female gender, the type of rearrangement and involved chromosome(s), and maternal age. We believe these data are instructive in the challenging medical genetic counseling of parents faced with no option other than transfer of an embryo with segmental mosaicism.

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Section: Parental Ages Of Segmental Mosaicism Carriersmentioning

confidence: 97%

“…Until recently, mosaic embryos had not been considered for transfer. Greco et al (2020) were the first to demonstrate that mosaic embryos may have the potential for giving birth to healthy offspring. Among mosaic embryos, one-third of the mosaic cases were segmental mosaics (Liu et al 2017;Nakhuda et al 2018;Coll et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Kovaleva¹,

Cotter²

2022

J Appl Genetics

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“…Several studies provide evidence that it is worth performing preimplantation genetic testing to detect aneuploidy in embryos generated from women of advanced age, and using this procedure, the live birth rate can be increased [ 130 , 131 , 132 , 133 , 134 ]. By contrast, two other studies reported that the latter-mentioned testing method did not positively influence the live birth rate in pregnant women below the age of 35 years [ 135 , 136 ].…”

Section: Spindle Formation Disturbances and The Clinical Relevance Of...mentioning

confidence: 99%

Chromosome Segregation in the Oocyte: What Goes Wrong during Aging

Wasielak-Politowska¹,

Kordowitzki

2022

IJMS

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Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 106 at birth), which diminishes throughout life until menopause around the age of 50 (approximately 103 oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan.

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“…This approach needs a single embryo intervention, and the zona can be targeted in a range far from the inner cell mass, decreasing its association in the biopsy method. The last approach mixes the previous techniques in which it consists of penetrating the zona when the blastocyst is completely expanded and then waiting for the TE herniation[4,5] (Greco., et al 2020). There are several molecular techniques to perform PGT-A, as shown in the table below.Molecular techniques Descriptions comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH) The method works through identifying alterations in the 24 chromosomes numbers and rearrangements when analysing the biopsied cells with a reference sample.…”

mentioning

confidence: 99%

“…Moreover, PGT-A aims to enhance the processes of a section of embryos for transfer and hence reduce the time to live birth(Wilding., et al 2019). On the other hand, some studies investigated how PGT-A can be cost-effective for couples attempting ART; for instance, a new study observed that IVF with PGT-A to be cost-effective for women over the age of 37 years, the study considered the exact cost estimations for all women > 37 years old and assumed that they would have received short-ening the time to pregnancy(Rubio., et al 2017) [6][7][8]. Likewise, a single-center observational-cohort study included a total of 2538 couples in the control group and 308 patients were into (PGT-A) group.…”

mentioning

confidence: 99%