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Disorders of genetic etiology exist in 2%-3% of live-born infants. Identifying couples with increased susceptibility for offspring with anomalies or genetic disorders is increasingly effective as a result of molecular advances. Preimplantation genetic testing (PGT) with the use of trophectoderm biopsy, 24-chromosome testing, and molecular testing have allowed wider applicability for avoiding a clinical pregnancy termination. Cell-free DNA in maternal blood is another targeted option, although invasive prenatal genetic diagnosis provides the greatest amount of genetic information. DNA-based methods to detect subtle chromosomal abnormalities are much more sensitive than traditional karyotypes and do not require cultured cells. Aneuploidy and structural chromosomal abnormalities can be readily detected with the use of small amounts of DNA, if necessary amplified, as in PGT. Novel approaches exist for detecting perturbations in single-gene disorders. Not only has the molecular basis for many monogenic disorders been elucidated, but modest costs for DNA sequencing has made testing feasible. As the number of testable genetic disorders has increased, principles underlying screening have advanced. Genetic screening for disorders of high incidence in certain ethnic groups was initiated decades ago; however, limitations exist, and reduction in live-born incidence is not infrequently small. Expanded carrier screening is now offered in panethnic fashion, extending surveillance to couples of mixed ethnicities and involving many more genetic conditions. Targeted gene panels (e.g., adult-onset cancer genes) further increase the number of genetic disorders amenable to screening, often leading to PGT., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Preimplantation genetic diagnosis (PGD) can be considered the earliest form of prenatal testing. It was first used in humans over 26 years ago. At its inception, PGD could only be performed for a limited number of genetic disorders. Technological advances in molecular biology and cytogenomics have been utilized in the field of PGD to greatly expand the spectrum of genetic disorders that can now be detected in early human embryos.

Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible. Prenatal genetic diagnosis via amniocentesis or chorionic villus sampling was used to determine the need for continuing fetal therapy (dexamethasone), allowing cessation if the fetus was unaffected. Newer methods now allow diagnosis earlier in gestation, further shortening the treatment time for unaffected female fetuses who will not develop genital ambiguity. Preimplantation genetic testing permits transfer only of an unaffected female or male fetus. Analysis of maternal cell-free DNA based on quantitative differences in the amount of allele parental DNA permits affected pregnancies to be differentiated from unaffected pregnancies., (Copyright © 2018. Published by Elsevier Inc.)

Prenatal treatment of congenital adrenal hyperplasia (CAH) has long involved prenatal treatment with dexamethasone, administered to the pregnant woman to prevent genital masculinization of an affected female fetus. Although it is unnecessary to treat unaffected or affected males because their genital development would not be disturbed, there has only been incremental progress in determining fetal gender sufficiently each to avoid treating males and unaffected females. Invasive procedures were initially necessary, with first-trimester amniocentesis at 15-20 weeks and then chorionic villus sampling (CVS) at 10-12 weeks gestation. Two approaches now allow personalized treatment of affected female fetuses prior to female genital differentiation. Only preimplantation genetic diagnosis (PGD) is available prior to clinical pregnancy. Recent technological advances have further allowed both single gene diagnosis (e.g., CAH) and aneuploidy detection concomitantly, resulting in far better pregnancy rates than heretofore possible in assisted reproduction technology., (Copyright © 2016. Published by Elsevier Ltd.)

Pre-implantation genetic diagnosis provides prenatal genetic diagnosis before implantation, thus allowing detection of chromosomal abnormalities and their exclusion from embryo transfer in assisted reproductive technologies. Polar body, blastomere or trophectoderm can each be used to obtain requisite genetic or embryonic DNA. Pre-implantation genetic diagnosis for excluding unbalanced translocations is well accepted, and pre-implantation genetic diagnosis aneuploidy testing to avoid repeated pregnancy losses in couples having recurrent aneuploidy is efficacious in reducing miscarriages. Controversy remains about whether pre-implantation genetic diagnosis aneuploidy testing improves take home pregnancy rates, for which reason adherence to specific indications is recommended while the issue is being adjudicated. Current recommendations are for obligatory 24 chromosome testing, most readily using array comparative genome hybridisation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This article reports the results from a study of couples participating in a research protocol in which IVF/preimplantation genetic diagnosis (PGD) was available for non-medical sex selection. The study sought to characterize the moral attitudes and beliefs of couples actively pursuing IVF/PGD solely for purposes related to sex selection. Eighteen couples participated in ethnographic interviews from November 2005 to April 2006. These interviews explored couples' motivations for pursuing sex selection, moral beliefs and attitudes regarding sex selection and sources of moral ambivalence about the use of IVF/PGD for sex selection. Couples reported a combination of motivations for pursuing sex selection, including a desire to limit family size, concerns about parental age and financial concerns about multiple pregnancies. Many couples compared their decision to choices about abortion, maintaining that individuals have a right to make such decisions privately. Couples frequently expressed anxiety about telling their other children and family members about their plans to use IVF/PGD for sex selection. Few couples cited concerns about the physical or emotional burdens of IVF/PGD. The study's findings suggest that couples pursuing IVF/PGD for sex selection view this as an ethically complex decision and express considerable uncertainty about the ethical acceptability of this practice., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

First reported in 1990, PGD has evolved into a complementary form of prenatal diagnosis offering novel indications. DNA for PGD can be recovered with equal safety and facility from polar bodies I and II, blastomere (8 cell embryo) and trophectoderm (5-6 day blastocyst). Diagnostic accuracy is very high (>99%) for both chromosomal abnormalities and single gene disorders. Traditional application of FISH with chromosome specific probes for detecting aneuploidy and translocations may be replaced or complemented by array comparative genome hybridization (array CGH); biopsied embryos can now be cryopreserved (vitrification) while analysis proceeds in orderly fashion. PGD has been accomplished for over 200 different single gene disorders. Novel indications for PGD not readily applicable by traditional prenatal genetic diagnosis include avoiding clinical pregnancy termination, performing preconceptional diagnosis (polar body I), obtaining prenatal diagnosis without disclosure of prenatal genotype (nondisclosure), diagnosing adult-onset disorders particularly cancer, and identifying HLA compatible embryos suitable for recovering umbilical cord blood stem cells., ((c) 2010 John Wiley & Sons, Ltd.)

The randomized clinical trial (RCT) is a powerful experimental design that when properly executed produces generalizable results. Conducting a RCT becomes complex when technical skills are required. Without requisite skills, a RCT may yield misleading results, an elegant RCT unwittingly generating spurious results due to technical inexperience. This pitfall is applicable to procedures used to evaluate assisted reproductive technologies. RCTs assessing the value of preimplantation genetic screening, also called preimplantation genetic diagnosis for aneuploidy testing--require three general prerequisites--proper study design, skilled operators (embryo biopsy), and skilled laboratory cytogeneticists (diagnosis). Lacking either of the latter two, even an elegantly designed RCT is not necessarily valid.

Professional societies that are stakeholders in preimplantation genetic diagnosis have democratically elected officers and favor self-regulation. Their practice guidelines are cognizant of societal needs and allow for introduction of new technologies. These societies have demonstrated the ability for professional self-regulation by collection, validation, and promulgation of center-specific results.

Preimplantation genetic diagnosis (PGD), the genetic testing of embryos developed through IVF is one of the fastest growing techniques in reproductive medicine and IVF. Some suggest that PGD will become part of every IVF cycle in the future. The growing popularity of PGD has highlighted the fact that there are no comprehensive data available about the use of PGD, its accuracy, or the health outcomes of babies born following PGD. For patients, practitioners, and policymakers alike, such information is critical. To address the gaps in knowledge, a working group of the leading experts in the development and practice of PGD and IVF has begun to design a database to collect information about PGD as practised in the United States.

Objective: To determine whether preimplantation genetic diagnosis (PGD) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage (RM) patients., Design: Controlled clinical study., Setting: In vitro fertilization centers and PGD reference laboratory., Patient(s): Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology., Intervention(s): Biopsy of a single blastomere from each day 3 embryo, followed by fluorescence in situ hybridization analysis., Main Outcome Measure(s): The rate of spontaneous abortions in RM subjects undergoing PGD were compared with [1] their own a priori expectations and [2] a comparison group of women undergoing PGD for advanced maternal age (> or =35 years)., Result(s): Before PGD, RM patients had lost 87% (262/301) of their pregnancies, with an expected loss rate of 36.5%. After, they only lost 16.7% pregnancies. This difference was mostly due to reduction in pregnancy loss in the > or =35-years age subgroup, to 12% from an expected 44.5%., Conclusion(s): Preimplantation genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy outcome in RM couples, especially those in which the woman is aged > or =35 years. Our data indicate that PGD reduces the risk of miscarriage in RM patients to baseline levels.

Unlabelled: Especially applicable for heritable neoplasia, preimplantation genetic diagnosis (PGD) is possible for any Mendelian disorder whose gene has been localized, whether the molecular basis is known or not., Methods and Results: PGD requires DNA from gametes (oocytes) or embryos before 6 days postconception, when implantation occurs. Approaches include 1) polar body biopsy, 2) blastomere biopsy (aspiration of one or two cells from the six- to eight-cell embryos at 2 or 3 days), and 3) trophectoderm biopsy, which allows recovery of 20 or more cells (20-50) from 125- to 150-cell, 5- to 6-day blastocysts. Of some 6000 PGD cycles worldwide, approximately 1500 have been performed for Mendelian indications. The approximately 25% live birth rates following PGD parallel the general U.S. experience for assisted reproductive technology. PGD has been accomplished for both cancer-specific disorders like adenomatous polyposis coli (APC), BRCA1, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome (VHL), as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome). PGD also makes possible the identification and, hence, transfer of embryos of specific HLA genotypes. This allows cord blood harvesting for stem cell implantation into a moribund child, often an older sibling of the fetus., Conclusions: PGD is a complex, but achievable, approach especially applicable to Mendelian forms of neoplasia. PGD is an attractive addition to the prenatal diagnostic armamentarium, especially relevant to heritable neoplasia. PGD also makes possible novel indications having special relevance to heritable neoplasia.

Background: Spatial organization of chromosomes is hypothesized to reflect transcriptional activity and regulatory protein function. Preimplantation genetic diagnosis allows assessment of the spatial relationship of chromosomes in human blastomeres. We thus examined the localization of chromosomes 13, 16, 18, 21, 22, X and Y in blastomeres from 6-8-cell stage embryos, correlating localization to aneuploidy and embryo morphology., Methods: Following fluorescence in situ hybridization to enumerate chromosomes 13, 16, 18, 21, 22, X and Y, signal positions were localized within one of four concentric shells. Statistical analysis compared chromosome localization between euploid and aneuploid blastomeres as well as morphologically normal and abnormal embryos., Results: Of 98 embryos, 109 blastomeres were evaluated. Within chromosomally normal blastomeres, no difference in the location of all seven chromosomes (P

Many couples are now seeking preimplantation genetic diagnosis (PGD) and fluorescence in-situ hybridization (FISH) as an alternative approach to avoid spontaneous abortion by ensuring transfer of presumed chromosomally normal embryos. This case report describes unexpected findings in a couple having three spontaneous abortions and two failed IVF cycles. In two IVF PGD cycles, four of 13 (30.8%) embryos (blastomeres) demonstrated duplication involving the Down syndrome critical region, detectable by a locus specific chromosome 21 probe. The same duplication was subsequently detected by FISH in 66 of 1002 (6.6%) sperm nuclei, demonstrating paternal gonadal mosaicism. Cytogenetic studies of peripheral blood revealed normal karyotypes in both the male and female partners. This identification of paternal germ cell or gonadal mosaicism suggests that analysis of sperm nuclei prior to undergoing IVF with PGD may be of value in patients with recurrent spontaneous abortions or multiple failed IVF.