@genetic-counselor
Genetic Counselor
Forum Replies Created
-
Posts
-
For trisomy 21, Non-Invasive Prenatal Testing achieves substantially higher sensitivity and a lower false-positive rate than conventional first-trimester combined screening, which is based on maternal age, nuchal translucency measurement, and biochemical markers. Sensitivity for trisomy 21, trisomy 18, and sex chromosome aneuploidies generally exceeds 97 to 100 percent, with specificity above 99 percent, in large validation cohorts. However, the positive predictive value varies significantly by condition: it is highest for trisomy 21 (commonly cited around 80 to 85 percent in tested populations), progressively lower for trisomy 18 and trisomy 13, and lowest for rare autosomal aneuploidies and copy number variants (often in the single digits to low double digits). This distinction is clinically important, a high-probability result on a genome-wide panel for a rare autosomal aneuploidy carries a much greater chance of being a false positive than the same result for trisomy 21. No screening test offers 100 percent accuracy, and a no-call or inconclusive result can occur due to insufficient fetal fraction. Every high-probability result should be routed through genetic counseling and confirmed with a diagnostic test before any decision regarding the pregnancy is made.
Basic Non-Invasive Prenatal Testing panels report on the three common autosomal trisomies: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome) — along with sex chromosome aneuploidies such as Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Genome-wide panels additionally report aneuploidy status for the remaining chromosomes (rare autosomal aneuploidies) and larger copy number variants, typically at a size cut-off of 5 to 7 megabases, depending on the laboratory’s platform, type of testing and validated reporting thresholds. Key limitations to communicate to patients: it remains a screening test, not a diagnostic one, so any high-probability result requires confirmation via amniocentesis or chorionic villus sampling before a clinical decision is made; it does not detect structural birth defects, single-gene disorders, or triploidy reliably and its accuracy depends on adequate fetal fraction, which can be reduced in women with a higher body mass index, in very early gestation, or in certain maternal conditions. As more chromosomes are screened, the likelihood of results arising from confined placental mosaicism, maternal mosaicism, or a co-existing maternal malignancy also increases, which is a specific counseling point for genome-wide panels.
Non-Invasive Prenatal Testing is offered to pregnant women across the risk spectrum, but specific groups derive particular benefit:
*Women with advanced maternal age (35 years or older at delivery)
*A prior pregnancy affected by a chromosomal condition
*An abnormal first-trimester combined screening result
*A family history of a chromosomal disorder
*An ultrasound soft marker suggestive of increased aneuploidy risk
The genome-wide option is worth discussing specifically with women who want screening beyond the three common trisomies, since it also reports on rare autosomal aneuploidies and select large copy number variants though this comes with a materially lower positive predictive value for these additional categories, which needs to be explained upfront. Women who wish to avoid the procedural miscarriage risk of invasive testing, while still obtaining a highly sensitive risk assessment, are also good candidates. It is not recommended as a substitute for diagnostic testing in women who already have a confirmed high-risk indication requiring definitive results. Though if the risk factor is showed to be high in NIPT, ultimately it leads to requiring invasive testing for confirmatory.Non-Invasive Prenatal Testing is a screening test performed on a maternal blood sample, usually collected after 10 weeks of pregnancy. During pregnancy, small fragments of placental DNA otherwise knows as cell-free fetal DNA, enter the mother’s bloodstream and circulate alongside her own cell-free DNA. Non-Invasive Prenatal Testing uses next-generation sequencing to analyze this mixed pool of DNA fragments and calculate the relative proportion contributed by the placenta, which serves as a proxy for fetal chromosome dosage. An excess or deficit in the expected proportion of DNA from a given chromosome indicates a possible aneuploidy. Initially, screening for aneuploidies for chromosomes 13, 18, 21, and sex chromosomal aneuploidies were available however, Genome-wide panels extend this analysis across all 23 pairs of chromosomes, rather than restricting it to chromosomes 13, 18, 21, X, and Y. Because the test only requires a maternal blood draw, it carries no procedural risk to the pregnancy, unlike invasive diagnostic procedures such as amniocentesis or chorionic villus sampling.
No. Direct-to-consumer kits are generally less comprehensive and not intended for medical diagnosis. Clinical genetic testing, ordered and interpreted by a geneticist, is more targeted, more rigorously validated, and appropriate for medical decision-making.
Yes, predictive testing is available for certain late-onset neurological conditions. Because these results carry significant emotional and life-planning implications, genetic counseling before and after testing is strongly recommended.
Yes. Since family history isn’t available, genetic testing can be especially useful for adopted children to identify or rule out inherited conditions and guide their medical care.
Generally, testing for conditions that only appear in adulthood, such as certain hereditary cancers, is deferred until the child is old enough to understand and decide for themselves, unless early knowledge would change medical care in childhood. This is an important discussion to have with a genetic counselor.
Yes, genetic information is treated as confidential medical data. It is shared only with you and the healthcare providers directly involved in your care, and is not disclosed to third parties without your consent.
*Biopsy and mosaicism: The trophectoderm biopsy samples only a few cells, which may not always represent the full embryo, particularly in mosaic embryos.
*No embryos may qualify for transfer: In women with diminished ovarian reserve or advanced maternal age, it is possible that no embryo is classified as euploid in a given cycle.
*Additional cost and time: The biopsy, genetic analysis, and typically an accompanying frozen embryo transfer add to the overall cost and duration of treatment.
*Does not test for all genetic conditions: Preimplantation Genetic Testing for Aneuploidy screens for chromosome number abnormalities only; it does not detect single-gene disorders (which require *Preimplantation Genetic Testing for Monogenic disorders) or structural rearrangements below its resolution threshold.
*Not a guarantee of pregnancy: A euploid result improves the odds but does not guarantee implantation or a live birth, as uterine, endocrine, and other factors also influence outcomes.Yes, with an important clarification on what “success” means. In women over 37 years, the proportion of chromosomally abnormal embryos rises steeply, often exceeding 60–70% of blastocysts formed. For this age group, current evidence shows Preimplantation Genetic Testing for Aneuploidy:
*Improves success per embryo transfer: Transferring a chromosomally normal (euploid) embryo yields significantly higher implantation and live birth rates per transfer compared to an untested embryo of similar grade, since the largest single cause of failure in this age group has been screened out.
*Reduces miscarriage rates: Since a majority of miscarriages in this age group are chromosomal in origin, transferring euploid embryos meaningfully lowers pregnancy loss rates.
*Shortens time to a successful pregnancy: By avoiding transfers of embryos destined to fail or miscarry, couples often reach a live birth in fewer transfer attempts.
*Does not increase the cumulative live birth rate per egg retrieval cycle: Preimplantation Genetic Testing for Aneuploidy does not create more euploid embryos, it identifies which existing embryos are euploid. If a woman over 37 years produces very few or no euploid embryos in a cycle, testing does not change that underlying biological reality.
for women over 37 years, Preimplantation Genetic Testing for Aneuploidy is most valuable for improving the efficiency and predictability of each transfer, not for increasing the total number of embryos available.*Women of advanced maternal age (typically 35 years and above)
*Couples with recurrent pregnancy loss
*Couples with a history of repeated In Vitro Fertilization implantation failure
*Couples where one partner carries a balanced chromosomal translocation or structural rearrangement
*Couples who wish to transfer a single embryo (elective single embryo transfer) while maintaining reasonable success rates
Consultation with a geneticist or genetic counselor will be helpful to see if PGT-A is necessary.Chromosomal aneuploidy is the leading cause of implantation failure and first-trimester miscarriage, and its incidence rises sharply with maternal age. By identifying which embryos are chromosomally normal before transfer, Preimplantation Genetic Testing for Aneuploidy allows clinicians to prioritize the embryo(s) with the highest biological likelihood of implanting and progressing to a healthy pregnancy, rather than selecting based on morphology (appearance) alone.
Preimplantation Genetic Testing for Aneuploidy (PGT-A) is a laboratory technique used alongside In Vitro Fertilization (IVF) to screen embryos for an abnormal number of chromosomes before they are transferred to the uterus. A small number of cells are biopsied from the trophectoderm (the outer layer of a day 5–6 blastocyst, a cluster of dividing cells that forms five to six days after a sperm fertilizes an egg) and analyzed using next-generation sequencing. Embryos are then classified as chromosomally normal (euploid), abnormal (aneuploid), or mosaic (a mix of normal and abnormal cell lines).
Screening tests estimate risk and tell you whether further testing may be needed; they don’t give a final answer. Diagnostic tests confirm or rule out a condition with much higher certainty. For example, in pregnancy, a screening test might flag increased risk, and a diagnostic test would then confirm whether the baby is actually affected.
