Figure 2
Nuclei from an embryo after PGS showing mitotic non-disjunction of chromosome 13 and other post-zygotic chromosomal abnormalities
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Preimplantation genetic screening (PGS) is used to determine the chromosome status of human embryos from patients with advanced maternal age (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF).
Embryos from 47 such couples were investigated for chromosomes 13, 15, 16, 18, 21 and 22 using fluorescence in situ hybridization with...
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Preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) using sequential in situ hybridization was applied for aneuploidy testing in 276 couples with 282 ART cycles. Patients with advanced maternal age (AMA, n = 147), recurrent implantation failure (RIF, n = 48), repeated early spontaneous abortion (RSA, n = 32) and abnormal gamete cell...
Among other factors, chromosomal abnormalities that originate from gametogenesis and preimplantation embryonic development are thought to be one of the major contributing factors for early embryonic death and failure of pregnancy. However, so far, no non-invasive technique exists that allows the detection of the chromosomal complement of an oocyte...
Citations
... The differences between the groups may be due to the fact that in Group 1 patients with guarded prognosis for a suitable embryonic development were recruited. Genetic diagnosis by PGT-A has shown to increase pregnancy rates by reducing the transference of embryos with chromosomal abnormalities, 14,15 as there are reports where high rates of aneuploidies may be related to causes of infertility 16,13 ; thus, the use of genetic diagnosis tools assures the embryo quality in patients with poor prognosis related to embryonic development. ...
... Contrary to the findings of this study, there are reports where the transference of one or multiple embryos does not show any effect on pregnancy rates. 16,17 Similarly to the evaluation of embryo quality, another critical point to achieve pregnancy is the embryo transfer, where the patient's physiological conditions have a critical role. Simon et al. 18 have reported that implantation failures have been poorly explored. ...
Background: In vitro Fertilization (IVF) is a tool for assisted reproduction used with the aim of increasing pregnancy rates in couples with infertility issues. These procedures may be optimized using techniques for genetical evaluation of the embryo by means of preimplantation genetic testing for aneuploidy (PGT-A) or diagnosis and correction of the uterine cavity such as Hysteroscopy. Objective: The objective of this study was to evaluate the impact of hysteroscopy in contrast with PGT-A analysis with respect to pregnancy rates on IVF cycles. Materials and methods: A study was carried out with Mexican patients during 2018-2021. Patients were divided in two groups: Group 1, patients with guarded prognosis for fertilization; Group 2, patients with guarded prognosis for implantation. The couples evaluated were subjected to different methodologies before IVF. Results: It was found that prior use of PGT-A or Hysteroscopy increase pregnancy rates by 9.4% up to 20.92%. In Group 1 the use of PGT-A/IVF caused a mean pregnancy rate of 77.7%, being favorable the transference of a single embryo. In Group 2, the best combination was Hysteroscopy/IVF with a pregnancy rate of 76.96%. Conclusion: Both of the methodologies prior to the IVF cycle improve pregnancy rates, being recommendable to carry out a PGT-A in patients with a poor genetic prognosis with the transference of a single embryo. Hysteroscopy is recommended when lesions or infectious processes are detected in the uterine cavity, and two-embryo transference is carried out.
... 24,28,29 A high percentage of embryos from IVF show a postzygotic origin of aneuploidy, leading to chromosomal mosaicism. 24,[30][31][32][33] Diploid-aneuploid mosaicism is the most common class in cleavage-stage embryos. 34 Mitotic errors in postzygotic division, such as anaphase lag and mitotic nondisjunction, may contribute to chromosome missegregation and aneuploidy. ...
Importance:
It is known that oocytes undergo aging that is caused by exposure to an aged ovarian microenvironment. Telomere length in mouse and bovine oocytes declines with age, and age-associated telomere shortening in oocytes is considered a sign of poor development competency. Women with advanced age undergoing assisted reproductive technologies have poor outcomes because of increasing aneuploidy rates with age. Research has shown that aneuploidy is associated with DNA damage, reactive oxygen species, and telomere dysfunction.
Objective:
In this review, we focus on the possible relationship between telomere dysfunction and aneuploidy in human early embryo development and several reproductive and perinatal outcomes, discussing the mechanism of aneuploidy caused by telomere shortening and fusion in human embryos.
Evidence acquisition:
We reviewed the current literature evidence concerning telomere dysfunction and aneuploidy in early human embryo development.
Results:
Shorter telomeres in oocytes, leukocytes, and granulosa cells, related to aging in women, were associated with recurrent miscarriage, trisomy 21, ovarian insufficiency, and decreasing chance of in vitro fertilization success. Telomere length and telomerase activity in embryos have been related to the common genomic instability at the cleavage stage of human development. Complications of assisted reproductive technology pregnancies, such as miscarriage, birth defects, preterm births, and intrauterine growth restriction, also might result from telomere shortening as observed in oocytes, polar body, granulosa cells, and embryos.
Conclusions and relevance:
Telomere length clearly plays an important role in the development of the embryo and fetus, and the abnormal shortening of telomeres is likely involved in embryo loss during early human development. However, telomere fusion studies have yet to be performed in early human development.
... 54 It has been demonstrated DovePress that trisomies and monosomies mostly have a meiotic origin, while nullisomies, mosaicism, haploidy and polyploidies mostly have a mitotic origin. [55][56][57] Sex chromosomes are specifically liable to meiotic non-disjunction; which is believed to be the mechanism of sperm aneuploidy, due to their unique structures, which provide only a few sites of recombination. 37 Normally, the abnormal cells that suffer from non-disjunction of sex chromosomes during meiosis I or II are subjected to a complete or partial meiotic arrest by the pachytene checkpoint mechanism. ...
... In such case, the first mitotic spindle will not form properly leading to failure of cytokinesis, creating two chromosomally abnormal cells. 51,52,[55][56][57] Mitotic errors could also be due to reduced expression of certain cell cycle checkpoint genes during early embryonic development or less functional cell cycle checkpoint mechanisms that may lead to chromosomal segregation errors in the first cleavages of human preimplantation embryos and thus to mosaicism. 53,63 Several other mechanisms have been proposed for the development of mosaic embryos with diploid or haploid cells, including cell fusion, nuclear division without previous chromosome duplication, incorporation of a polar body nucleus into a diploid embryo, incorporation of a second sperm (n) nucleus into a haploid embryo. ...
Purpose
The aim of this study is to evaluate the effect of abnormal semen morphology on the frequency of sex chromosomal abnormalities in embryos obtained by ICSI, which represents the first to be studied in Egyptian population.
Methods
Forty-two couples suffering from male infertility due to teratozoospermia were divided into two groups: patients with severe and moderate teratozoospermia (group A and B, respectively). All involved couples were subjected to careful history taking and had a normal clinical examination and karyotype. Females were subjected to hormonal assays, pelvic ultrasound, hysterosalpingography and yielded normal results, while male partners were subjected to computerized semen analysis. Preimplantation genetic diagnosis was performed for all suitably developed embryos including embryo biopsy, fixation of biopsied cells and fluorescent in situ hybridization (FISH) analysis.
Results
Couples included in the two groups were found to be homogenous in terms of age of both partners and duration of infertility. Interpretation of FISH results was performed by evaluation of embryos’ chromosomal constitution as regards abnormalities in chromosomes X, Y and 18. Twenty-seven embryos (48.2%) were found chromosomally abnormal in group A, while only 14 embryos (25.0%) were found chromosomally abnormal in group B. Aneuploidies involved only sex chromosomes were tripled in group A embryos when compared to their frequency in group B embryos (26.8% and 8.3%, respectively) with statistically significant difference between the two groups (p=0.002). Monosomies were the most common type of aneuploidy and were significantly higher in group A (14.3%) when compared to group B (3.6%) (p=0.047). Embryos with mosaic abnormalities were more common in group A (12.5%) when compared to group B (3.6%), however not statistically significantly different (p= 0.162). A significant difference between the two studied groups as regards the total number of potentially viable chromosomal abnormalities detected and the potentially viable sex chromosomal aneuploidies detected (p<0.001 and p=0.002), respectively.
Conclusion
The cases with severe teratozoospermia undergoing ICSI treatment can display a higher rate of sex chromosome aneuploidies in their embryos (threefold) than cases with moderate teratozoospermia.
... The true clinical significance of carrying these heteromorphisms and their impact on human gametes and post-fertilization embryo development has not yet been fully elucidated. Several studies have reported a higher incidence of these variants in couples, affecting both male and females suffering from infertility, recurrent pregnancy loss, or reproductive failure (Šípek et al., 2014;Morales et al., 2016;Düzcan et al., 2003;Madon et al., 2005;Iyer et al., 2007;Sahin et al., 2008;Akbaş et al., 2012;Delhanty et al., 1997;Mantzouratou et al., 2007). However, the relationship between chromosomal heteromorphisms and embryonic chromosomal composition in ART treatments remains predominantly speculative. ...
Objective:
Although chromosomal heteromorphisms are commonly found in the general population, some researchers have suggested a correlation with higher rates of embryo aneuploidy. This study aimed to assess the rates of embryo aneuploidy in couples who carry a chromosome heteromorphism.
Methods:
The study included couples who had G-banding karyotype testing and underwent an IVF/PGT-A cycle between January 2012 and March 2018. The participants were classified by couple karyotype: Group A: ≥1 patient reported to be a heterochromatic variant carrier; Group B: both partners reported to be "normal". We assessed the rates of aneuploidy among the groups. We ran a multivariate regression analysis to assess the relationship between heterochromatic variants and the rates of embryo aneuploidy.
Results:
Of the 946 couples analyzed, 48 (5.0%) reported being a carrier of ≥1 heterochromatic variant. We had 869 IVF/PGT-A cycles included in the analysis (Group A: n=48; Group B: n=82). There were no significant differences in embryo ploidy rates among the groups. The heterochromatic chromosome variant was not associated with increased likelihoods of aneuploidy (OR=1.04, CI:95% 0.85- 1.07; p=0.46). Finally, the gender of the heterochromatic variant carrier had no association with increased likelihood of aneuploidy (OR 1.02, CI 95% 0.81-1.28, p=0.82).
Conclusions:
Our study showed no association between parental heterochromatic chromosome variants and subsequent embryo aneuploidy rates. Ploidy rates do not appear to be negatively associated with couples when at least one patient is reported to be a carrier of a heterochromatic variant on the karyotype.
... In the present study, we found that the chromosomal abnormality types in the iRPL group tended to depend on maternal age, with higher rates of trisomy in women aged %35 years and of complex aneuploidy with R2 chromosomes in women aged >35 years. Previous studies have shown that most aneuploidies, such as trisomy and complex aneuploidy, were due to errors in maternal meiosis (37,38). In addition, the incidence of meiotic errors increased exponentially with maternal age (39). ...
Objective
To determine whether the incidence of chromosomal abnormalities in blastocysts is higher in patients with idiopathic recurrent pregnancy loss (iRPL) who underwent preimplantation genetic testing for aneuploidy (PGT-A) than in those who underwent preimplantation genetic testing for monogenic defects (PGT-M).
Design
Retrospective cohort study.
Setting
University-affiliated reproductive center.
Patient(s)
A total of 62 patients with iRPL underwent 101 PGT-A cycles (iRPL group), and 212 patients underwent 311 PGT-M cycles (control group).
Interventions(s)
Blastocyst biopsy and comprehensive chromosome screening technologies, including single-nucleotide polymorphism microarrays and next-generation sequencing.
Main Outcome Measure(s)
Incidence of chromosomal abnormalities in blastocysts and clinical miscarriage (CM) rate.
Result(s)
Stratification analysis by maternal age showed an increased incidence of chromosomal abnormalities in the iRPL group aged ≤35 years (48.9% vs. 36.9%), whereas no significant increase was found in the iRPL group aged >35 years (66.9% vs. 61.4%). After transfer of euploid embryos, women aged ≤35 years with iRPL exhibited an increased CM rate compared with the control group (26.1% vs. 3.1%).
Conclusion(s)
Young patients with iRPL have a significantly higher rate of chromosomal abnormalities in blastocysts compared with patients with no or sporadic CM. Although euploid embryos were transferred after PGT-A, young patients with iRPL had a higher CM rate, which may indicate that chromosomal abnormalities might not be the only causal factor for iRPL. Therefore, the role of PGT-A in iRPL still needs to be clarified.
... A classic example is a diploid/ heterozygous chimera that defines a mixture of diploid and aneuploid cell lines within the same embryo. Mantzouratou et al. found higher rates of diploid/heterozygous chimeric embryos in women with a history of recurrent implantation failure [5]. And Spinella et al. found mosaic embryos with low aneuploidy percentages (< 50%) had higher chances of implanting and developing to term, compared with embryos that had higher mosaicism levels (> 50%) [6]. ...
Purpose:
To compare chromosomal aberrations and aneuploidy features in (i) blastocysts following intracytoplasmic sperm injection (ICSI) and trophectoderm (TE) biopsy using preimplantation genetic screening (PGS) and (ii) early spontaneous abortion chorionic villus biopsies (SA-CVB) using single-nucleotide polymorphism (SNP) array detection.
Methods:
We retrospectively reviewed the data for 1014 TEs from 220 PGS cycles and 1724 SA-CVBs originating from naturally pregnant couples and patients undergoing assisted reproductive technology (ART) during 2017 to 2018. SNP array was applied in both PGS and SA-CVBs detection. Aberrations were defined, and the frequency and ratio of each chromosome aberration were compared between the two groups.
Results:
There were more abnormalities in TEs in the form of complex chromosome aneuploidies and monosomies, while SA-CVBs had more trisomies, sex chromosome abnormalities, and polyploidies. In both groups, chromosomal aneuploidies (including monosomies and trisomies) were confined to chromosomes 14, 15, 16, 18, 21, and 22, but showed varying distributions across the groups. Aneuploidy of chromosome 22 was most frequent in TEs, whereas that of chromosome 16 predominated in SA-CVBs. Among the sex chromosome abnormalities, X monosomies were significantly more prevalent in SA-CVBs.
Conclusions:
Chromosomal aberrations and aneuploidy manifested specific characteristics that differed between TEs and SA-CVBs, which indicates that distinct chromosomal abnormalities can affect certain developmental stages of embryos. Further analysis is needed to explore the chromosomal mechanisms affecting embryo development and implantation. Such information will help clinical assessments in prenatal diagnosis and reduce the incidence of genetically abnormal fetuses.
... The risk of embryonic aneuploidies leading to miscarriage or congenital disorders generally increases with maternal age [4][5][6][7]. The overall incidence of chromosomal anomalies in neonates is approximately one out of 160 births [8][9][10][11][12]. ...
Chromosomal segregation errors in germ cells and early embryonic development underlie aneuploidies, which are numerical chromosomal abnormalities causing fetal absorption, developmental anomalies, and carcinogenesis. It has been considered that human aneuploidy disorders cannot be resolved by radical treatment. However, recent studies have demonstrated that aneuploidies can be rescued to a normal diploid state using genetic engineering in cultured cells. Here, we summarize a series of studies mainly applying genome editing to eliminate an extra copy of human chromosome 21, the cause of the most common constitutional aneuploidy disorder Down syndrome. We also present findings on induced pluripotent stem cell reprogramming, which has been shown to be one of the most promising technologies for converting aneuploidies into normal diploidy without the risk of genetic alterations such as genome editing-mediated off-target effects.
... Microscopic analysis and scoring of FISH signals were carried out using an epifluorescence Olympus microscope (Olympus BX 40, London, UK). FISH signals were scored according to [8] Analysis by array-CGH For both diagnosis and follow up cells were subjected to aCGH using 24Sure + arrays (BlueGnome Ltd., Fulbourn, Cambridge UK, now Illumina). Prior to the aCGH, whole genome amplification was carried out using the Sureplex TM amplification kit (BlueGnome Ltd., Fulbourn, Cambridge UK, now Illumina). ...
... Microscopic analysis and scoring of FISH signals were carried out using an epifluorescence Olympus microscope (Olympus BX 40, London, UK). FISH signals were scored according to [8] Analysis by array-CGH For both diagnosis and follow up cells were subjected to aCGH using 24Sure + arrays (BlueGnome Ltd., Fulbourn, Cambridge UK, now Illumina). Prior to the aCGH, whole genome amplification was carried out using the Sureplex TM amplification kit (BlueGnome Ltd., Fulbourn, Cambridge UK, now Illumina). ...
Background: Reciprocal Y autosome translocations are rare but frequently associated with male infertility. We
report on the meiotic outcome in embryos fathered by two males with the karyotypes 46,X,t(Y;4)(q12;p15.32) and
46,X,t(Y;16)(q12;q13). The two couples underwent preimplantation genetic diagnosis (PGD) enabling determination of the segregation types that were compatible with fertilization and preimplantation embryo development. Both PGD and follow up analysis were carried out via fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (aCGH) allowing the meiotic segregation types to be determined in a total of 27 embryos.
Results: Interestingly, it was seen that the number of female embryos resulting from alternate segregation with the
chromosome combination of X and the autosome from the carrier gamete differed from the corresponding balanced males with derivative Y and the derivative autosome by a ratio of 7:1 in each case (P = 0.003) while from the adjacent-1 mode of segregation, the unbalanced male embryos with the combination of der Y and the autosome were seen in all embryos from couple A and in couple B with the exception of one embryo only that had the other chromosome combination of X and derivative autosome (P = 0.011). In both cases the deficit groups have in common the der autosome chromosome that includes the segment Yq12 to qter.
Conclusion: The most likely explanation may be that this chromosome is associated with the X chromosome at PAR2 (pseudoautosomal region 2) in the sex-body leading to inactivation of genes on the autosomal segment that are required for the meiotic process and that this has led to degeneration of this class of spermatocytes during meiosis.
... В 2011 г. A. Musters и соавт. [12], проведя анализ опубликованных данных, отобрали 4 обсервационных исследования [8,[13][14][15], в которые была включена 181 пациентка с привычным невынашиванием беременности. Среднее число предыдущих выкидышей колебалось от 2,8 до 4,7, а средний возраст женщин варьировал от 35,4 до 37,6 года. ...
