P.R. Brezina

Preimplantation genetic testing

#### Summary points Preimplantation genetic (PG) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilisation (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PG testing was first described in 1990 when the sex of cleavage stage embryos in two couples, both with X linked diseases, was determined.1 The applications and use of various types of PG testing have continued to increase. However, the benefits and limitations of PG testing, both in popular culture and the medical community, are often misunderstood. This article reviews the technologies available in PG testing, and discusses the risks, ethical considerations, appropriateness, and controversy surrounding its use in different clinical situations. #### Sources and selection criteria The information sources used to compile this …

The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies

Background. While assisted reproductive technology (ART), including in vitro fertilization has given hope to millions of couples suffering from infertility, it has also introduced countless ethical, legal, and social challenges. The objective of this paper is to identify the aspects of ART that are most relevant to present-day society and discuss the multiple ethical, legal, and social challenges inherent to this technology. Scope of Review. This paper evaluates some of the most visible and challenging topics in the field of ART and outlines the ethical, legal, and social challenges they introduce. Major Conclusions. ART has resulted in a tectonic shift in the way physicians and the general population perceive infertility and ethics. In the coming years, advancing technology is likely to exacerbate ethical, legal, and social concerns associated with ART. ART is directly challenging society to reevaluate the way in which human life, social justice and equality, and claims to genetic offspring are viewed. Furthermore, these issues will force legal systems to modify existing laws to accommodate the unique challenges created by ART. Society has a responsibility to ensure that the advances achieved through ART are implemented in a socially responsible manner.

Clinical applications of preimplantation genetic testing

Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most.

Classic and Cutting-Edge Strategies for the Management of Early Pregnancy Loss

There are few conditions in medicine associated with more heartache to patients than recurrent pregnancy loss (RPL). The management of early RPL is a formidable clinical challenge for physicians. Great strides have been made in characterizing the incidence and diversity of this heterogeneous disorder, and a definite cause of pregnancy loss can be established in more than half of couples after a thorough evaluation. In this review, current data are evaluated and a clear roadmap is provided for the evaluation and treatment of RPL.

Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis

OBJECTIVE To obtain embryonic molecular karyotypes from genomic DNA (deoxyribonucleic acid) isolated from blastocoel fluid (BF) and to compare these karyotypes with the karyotypes from the remaining inner cell mass (ICM) and trophectoderm (TE) of the blastocyst. DESIGN Prospective cohort study. SETTING Academic center and preimplantation genetics laboratory. PATIENT(S) Ninety-six donated cryopreserved embryos. INTERVENTION(S) Embryo biopsy, BF aspiration, DNA analysis using a comparative genomic hybridization microarray (aCGH). MAIN OUTCOME MEASURE(S) The aCGH of a single blastomere, BF-DNA, and ICM-TE. RESULT(S) The BF-DNA samples resulted in a successful aCGH in 63% of cases. Discordance in karyotypes was found between the BF-DNA and the ICM-TE in 52% of cases. A total of 70% of aneusomic (mosaicism), cleavage-stage embryos differentiated into euploid blastocysts. Probabilities for diagnostic accuracy were calculated and demonstrated the following: sensitivity of 0.88 (95% confidence interval [CI]: 0.62-0.98); specificity of 0.55 (95% CI: 0.39-0.70); positive predictive value of 0.41 (95% CI: 0.25-0.60); negative predictive value of 0.92 (95% CI: 0.75-0.99). CONCLUSION(S) Genomic DNA from the BF can be amplified and characterized by comprehensive chromosome microarrays. The results demonstrated that aneusomic cleavage-stage embryos differentiated into euploid blastocysts, possibly using a mechanism that marginalizes aneuploid nuclei into the blastocoel cavity. In addition, owing to the high discordance between the karyotypes obtained from the BF-DNA and the ICM-TE, using BF-DNA for preimplantation genetic testing is not yet advised.

At home testing: optimizing management for the infertility physician

OBJECTIVE To review and describe various over-the-counter testing products available to the infertility patient, a billion-dollar a year industry that continues to grow. DESIGN Methodology involved a detailed Medline search of literature, use of online search engines, and focused communications with various manufacturers to determine the usefulness and validity of existing products. CONCLUSION(S) Although some home tests have been subjected to scientific scrutiny, others have not. At-home testing represents an opportunity for physicians to involve patients actively in their care. When properly used, these tests also may result in cost savings. However, physicians and consumers must understand the limitations of these tests. Many of the technologies used are innovative and, with proper evaluation and implementation, could serve as valuable adjuncts to medical practice.

Preimplantation genetic testing for aneuploidy: what technology should you use and what are the differences?

PurposeThe purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a clear and balanced manner the various strengths and weaknesses of these technologies.MethodsA systematic literature review was conducted. We used the terms “preimplantation genetic testing,” “preimplantation genetic diagnosis,” “preimplantation genetic screening,” “preimplantation genetic diagnosis for aneuploidy,” “PGD,” “PGS,” and “PGD-A” to search through PubMed, ScienceDirect, and Google Scholar from the year 2000 to April 2016. Bibliographies of articles were also searched for relevant studies. When possible, larger randomized controlled trials were used. However, for some emerging data, only data from meeting abstracts were available.ResultsPGS is emerging as one of the most valuable tools to enhance pregnancy success with assisted reproductive technologies. While all of the current diagnostic platforms currently available have various advantages and disadvantages, some platforms, such as next-generation sequencing (NGS), are capable of evaluating far more data points than has been previously possible. The emerging complexity of different technologies, especially with the utilization of more sophisticated tools such as NGS, requires an understanding by clinicians in order to request the best test for their patients..ConclusionUltimately, the choice of which diagnostic platform is utilized should be individualized to the needs of both the clinic and the patient. Such a decision must incorporate the risk tolerance of both the patient and provider, fiscal considerations, and other factors such as the ability to counsel patients on their testing results and how these may or may not impact clinical outcomes.

Fertility Preservation in the Age of Assisted Reproductive Technologies

The desire to reproduce is one of the strongest human instincts. Many men and women in our society may experience situations that compromise their future fertility. The past several decades have seen an explosion of technologies that have changed the historical limitations regarding fertility preservation. This review offers an overview of the state of the art within fertility preservation including surgical and medical interventions and therapies that necessitate the need for cryopreservation of eggs, sperm, and embryos. The review also addresses the psychological consequences of banking/not banking materials among patients in need of fertility preservation, particularly in the oncofertility context.

Increased IVF pregnancy rates after microarray preimplantation genetic diagnosis due to parental translocations

Abstract We successfully performed preimplantation genetic diagnosis (PGD) and simultaneous preimplantation genetic screening (PGS) using single nucleotide polymorphism (SNP) microarrays for couples with balanced chromosome rearrangements in China. A total of 428 molecular karyotypes were diagnosed from 62 couples undergoing 68 in vitro fertilization (IVF) cycles. Of these, 48.1% of the embryos were chromosomally normal without translocation errors or aneuploidy. Of the 428 total embryos, 18.0% embryos were euploid, but were imbalanced due to the transmission of single translocation chromosome derivatives. A total of 6.5% of the embryos had chromosome abnormalities involving the parental chromosome aberration and other chromosomes aneuploidies. Significantly, 27.4% of the embryos were normal/balanced for the rearranged chromosomes, but were abnormal due to aneuploidy affecting other chromosomes. When evaluated on a per IVF cycle basis, 84% of the cycles had at least one chromosomally normal embryo available for uterine transfer. The clinical pregnancy rate per IVF cycle was 54%. Diagnosing genomically balanced embryos through 24 chromosome SNP microarray PGD/PGS, rather than minimally targeted fluorescence in situ hybridization (FISH), is a promising strategy to maximize the pregnancy potential of patients with known parental chromosomal translocations. Moreover, this is the first study to report the clinical application of SNP arrays to screen all 24 chromosome pairs of blastomeres and trophectoderm cells from patients carrying reciprocal translocations in China.

Preimplantation Genetic Screening: A Practical Guide

The past several decades have seen tremendous advances in the field of medical genetics. The application of genetic technologies to the field of reproductive medicine has ushered in a new era of medicine that is likely to greatly expand in the coming years. Concurrent with an in vitro fertilization (IVF) cycle, it is now possible to obtain a cellular biopsy from a developing embryo and genetically evaluate this sample with increasing sophistication and detail. Preimplantation genetic screening (PGS) is the practice of determining the presence of aneuploidy (either too many or too few chromosomes) in a developing embryo. However, how and in whom PGS should be offered is a topic of much debate.