Non-Invasive Prenatal Testing (NIPT)
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
SNP-based NIPT is based on specific amplification and sequencing of single-nucleotide polymorphisms (SNPs). SNPs are the most common genetic variation in the human genome, and each SNP represents a change in one nucleotide (31). Informative SNPs are those for which the mother is homozygous and the fetus is heterozygous, so parental genomic DNA is needed for this method. The required maternal genomic DNA is obtained from the leukocyte layer formed after centrifugation of whole blood samples. Paternal genomic DNA is optional, and can be obtained from a blood or a buccal swab sample. All samples undergo PCR amplification specific to selected SNPs, and PCR products are then sequenced. A specific algorithm subtracts parental genomic information to deduce placental DNA data and determine the copy number of each interrogated chromosome (32,33). The number of sequencing reads obtained in SNP-based NIPT is 6 million reads per sample on average (32,34). This approach also enables the reporting of deletions and microdeletions (35). Among NIPT, the SNP-based method demonstrates the greatest accuracy in SCA detection. It is also the only method capable of detecting triploidy. Furthermore, SNP-based NIPT does not detect off-target abnormalities.
Second-trimester screening for fetal abnormalities
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
In counseling patients, it is important to emphasize that multiple maternal serum screening protocols were developed primarily to detect trisomy 21, and the patterns of serum markers observed in pregnancies affected by trisomy 18 and other fetal chromosomal abnormalities are different. In trisomy 18, MSAFP and unconjugated estriol are low; however, in contrast to Down syndrome, hCG value is low as well. Although these results are well correlated with trisomy 18, a positive second-trimester serum screen has poor sensitivity and poor prediction for trisomy 18 (12). By contrast, genetic ultrasound to evaluate for characteristic sonographic findings associated with this diagnosis is highly sensitive in identifying fetuses with the disorder (13,14). Ultrasound evaluation of fetuses with trisomy 18 will be discussed later in this chapter. Trisomy 13 is usually associated with normal levels of all three maternal serum markers, except in cases where open fetal defects are present. In fetal triploidy, all three biochemical markers are low. Table 4 summarizes the changes in serum marker levels in various fetal chromosomal abnormalities.
Gestational Trophoblastic Neoplasia
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Partial hydatidiform moles are genetically nearly all triploid or rarely, tetraploid, with at least two paternal chromosome sets but also some maternal contribution (Figure 23.2c). Although triploidy occurs in 1–3% of all recognized conceptions and in about 20% of spontaneous abortions with abnormal karyotype, triploids due to two sets of maternal chromosomes do not become PHMs.24,25 Flow cytometry, in situ ploidy, or genotyping done from formalin-fixed, paraffin-embedded tissues15 can all therefore help in differentiating CHM from PHM, and PHM from diploid non-molar hydropic abortions.26 Although a variety of reports indicated that diploid PHM exists, genetic analysis of lesions suspected to be such has not supported this suggestion. In general, a diploid molar gestation is believed to be a complete hydatidiform mole.27 In PHMs, swelling tends to be less intense than in CHM and affects only some villi (partial). Thus, two populations of villi usually exist in a partial mole. Both swollen and non-swollen villi can have trophoblastic hyperplasia, which is mild and focal.28–30 Nuclear atypia is infrequent. The villi have characteristic indented or scalloped outlines and round inclusions.31
Thiol/Disulfide Homeostasis in Patients with Molar Pregnancies
Published in Fetal and Pediatric Pathology, 2020
Meryem Kuru Pekcan, Aytekin Tokmak, Nazli Topfedaisi Ozkan, Gulnur Ozaksit, Arzu Kosem, Ozcan Erel, Mutlu Meydanli
PHM and CHM are identified through histopathologic examination of molar tissue, presence or absence of fetal or embryonic tissue, as well as genetic studies. It is well known that all chromosomes in CHM are diploid (46 XX/46 XY) and paternal in origin. Similarly, in PHM, the extra sets of chromosomes are generally paternal in origin and triploidy is present (69XXY/69XYY/69XXX) [2]. Although the genetic basis of the disease is well known, there may be also environmental factors that disturb the oocyte and/or sperm structurally or functionally, such as OS. Perhaps the imbalance between the oxidant/antioxidant defense systems during the pre-pregnancy period may potentiate the development of molar pregnancies by disrupting the physiologic mechanisms that occur during the fertilization and post-fertilization periods.
Is the presence of corpus callosum predictable in the first trimester?
Published in Journal of Obstetrics and Gynaecology, 2018
Hakan Kalaycı, Ebru Tarım, Halis Özdemir, Tayfun Çok, Ayşe Parlakgümüş
This is the first study to include PCA screening as well as MB and F measurements. Pati et al. (2012) visualised PCAs at gestational weeks 12–20 in 71 patients. They measured the length of the PCAs and found a correlation with gestational week. In addition, the presence of the CC was confirmed by ultrasonography after gestational week 22. Díaz-Guerrero et al. (2013) searched 150 patient records for PCAs and detected the PCA path in 97.2% of their patients (144/150), which agreed with our study results (98%). Two of 150 patients had abnormal PCA paths with confirmation of ACC in the second trimester. Two other foetuses had triploidy, and a third had trisomy 13. In contrast, in our study, two patients with normal PCA paths had trisomy 13, and the other had trisomy 21.
Unexplained total abnormal fertilization of donor oocytes in ICSI with using spermatozoa from different patients
Published in Gynecological Endocrinology, 2019
Hripsime Grigoryan, Lev Levkov, Romualdo Sciorio, Eduard Hambartsoumian
Zygotes with triploid pronuclei (3PN) can cleave and some of them even can develop to blastocysts, which after the embryo transfer usually result in implantation failure or early pregnancy loss. The advent of assisted reproductive technology (ART) has provided an important insight into the mechanisms of normal and aberrant fertilization of human oocytes. Triploidy can appear either from dispermic fertilization or from retention of the second polar body extrusion. However, etiopathogenetic mechanisms, which lead to triploidy with digynic embryos (containing two maternal pronuclei) are not well understood.
Related Knowledge Centers
- Agenesis of The Corpus Callosum
- Central Nervous System
- Chromosome Abnormality
- Holoprosencephaly
- Ventriculomegaly
- Miscarriage
- Hydrocephalus
- Chromosome
- Mosaic
- Chiari Malformation
- Agenesis of The Corpus Callosum