An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age.

Objective: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age?

Design: Decision tree model.

Population: A randomised clinical trial on PGT-A (ESTEEM study).

Methods: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A.

DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro.

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs.

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial.

Study Question: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis?

Summary Answer: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years.

What Is Known Already: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial.

Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder.

RLIM, also known as RNF12, is an X-linked E3 ubiquitin ligase acting as a negative regulator of LIM-domain containing transcription factors and participates in X-chromosome inactivation (XCI) in mice. We report the genetic and clinical findings of 84 individuals from nine unrelated families, eight of whom who have pathogenic variants in RLIM (RING finger LIM domain-interacting protein). A total of 40 affected males have X-linked intellectual disability (XLID) and variable behavioral anomalies with or without congenital malformations.

Nanostructure and Microstructure Fabrication: From Desired Properties to Suitable Processes.

When designing a new nanostructure or microstructure, one can follow a processing-based manufacturing pathway, in which the structure properties are defined based on the processing capabilities of the fabrication method at hand. Alternatively, a performance-based pathway can be followed, where the envisioned performance is first defined, and then suitable fabrication methods are sought. To support the latter pathway, fabrication methods are here reviewed based on the geometric and material complexity, resolution, total size, geometric and material diversity, and throughput they can achieve, independently from processing capabilities.

Embryo selection and democratic control.

Recently, American colleagues called for a systematic collection of anonymized data on how many embryos and foetuses are deselected per institution per year, and for which conditions. These authors argued that if this information would be reported to a government agency or international body, the information would provide a baseline against which jurisdiction-specific trends in selection could be assessed. People who have disabilities, together with other key stakeholders, laypeople and experts, would then be in a position to assess the social impact of human selecting technologies and to make recommendations for action to mitigate negative effects as appropriate.

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing.

Recent developments in genetics and medically-assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing.

Healthy children without fear: Reproductive options for patients or couples carrying inherited diseases.

Prenatal diagnostics and preimplantation genetic screening are safe and efficient methods to help parents with inherited mutations for severe diseases to have healthy children. Its expansion into adult‐onset diseases and cancer raises challenges for regulation of assisted reproductive technologies and coverage by healthcare systems. [Image: see text]

PGD for the m.14487 T>C mitochondrial DNA mutation resulted in the birth of a healthy boy.

We report on the first PGD performed for the m.14487 T>C mitochondrial DNA (mtDNA) mutation in the MT-ND6 gene, associated with Leigh syndrome. The female carrier gave birth to a healthy baby boy at age 42.

DNA Methylation Profiling of Uniparental Disomy Subjects Provides a Map of Parental Epigenetic Bias in the Human Genome.

Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean.

The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists.

Study Question: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0?

Study Finding: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS.

Preimplantation genetic screening 2.0: the theory.

During the last few years a new generation of preimplantation genetic screening (PGS) has been introduced. In this paper, an overview of the different aspects of this so-called PGS 2.0 with respect to the why (what are the indications), the when (which developmental stage, i.

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy.

Study Question: How has the interface between genetics and assisted reproduction technology (ART) evolved since 2005?

Summary Answer: The interface between ART and genetics has become more entwined as we increase our understanding about the genetics of infertility and we are able to perform more comprehensive genetic testing.

What Is Known Already: In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and ART and published an extended background paper, recommendations and two Editorials.

Study Design, Size, Duration: An interdisciplinary workshop was held, involving representatives of both professional societies and experts from the European Union Eurogentest2 Coordination Action Project.

Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors.

Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus.

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer.

Study Question: How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)?

Summary Answer: BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages.

What Is Known Already: Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves.

Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature.

The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls.

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs.

Fertility preservation in female classic galactosemia patients.

Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group.

PGD for hereditary breast and ovarian cancer: the route to universal tests for BRCA1 and BRCA2 mutation carriers.

Preimplantation Genetic Diagnosis (PGD) is a method of testing in vitro embryos as an alternative to prenatal diagnosis with possible termination of pregnancy in case of an affected child. Recently, PGD for hereditary breast and ovarian cancer caused by BRCA1 and BRCA2 mutations has found its way in specialized labs. We describe the route to universal single-cell PGD tests for carriers of BRCA1/2 mutations.