Factors influencing the clinical outcome of preimplantation genetic testing for polycystic kidney disease.

Study Question: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)?

Summary Answer: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome.

What Is Known Already: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility.

Study Design, Size, Duration: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017.

Body composition and blood pressure in 6-year-old singletons born after pre-implantation genetic testing for monogenic and structural chromosomal aberrations: a matched cohort study.

Study Question: Does Day 3 embryo biopsy for pre-implantation genetic testing for monogenic (PGT-M) and structural chromosomal aberrations (PGT-SR) affect body composition and blood pressure readings of 6-year-old singletons?

Summary Answer: This study of 87 PGT-M and PGT-SR conceived singletons showed no differences in anthropometric measurements and blood pressure readings in comparison with a matched cohort of peers born after ICSI without embryo biopsy.

What Is Known Already: While neonatal outcomes after PGT conception have been found comparable to those after ICSI without embryo biopsy, only a few studies have reported outcomes after PGT at older ages. Moreover, embryo biopsy is also applied in couples who opt for PGT-M and PGT-SR and hence are not necessarily infertile.

Blurring boundaries. Interviews with PGT couples about comprehensive chromosome screening.

Objective: Comprehensive chromosome examination is a promising approach to Preimplantation Genetic Testing (PGT). Next to testing of specific chromosomes, such as in the case of reduced fertility due to chromosomal translocations, it allows testing of all chromosomes. Hence it potentially reduces the time to pregnancy and the risk of miscarriage.

Expanding the clinical spectrum of biallelic ZNF335 variants.

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.

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.

Depression, pregnancy-related anxiety and parental-antenatal attachment in couples using preimplantation genetic diagnosis.

Study Question: Do preimplantation genetic diagnosis (PGD) couples experience higher levels of stress during pregnancy and the perinatal period compared with couples who conceive spontaneously (SC) or with ICSI?

Summary Answer: PGD couples did not experience more psychological stress during pregnancy and beyond than ICSI or SC couples.

What Is Already Known: Previous studies have shown that assisted reproduction technology (ART) couples are more prone to pregnancy-related anxieties than SC couples, but display depressed feelings to an equal or lesser extent. However, only one study has focused on a female PGD sample, which may be a more vulnerable group than other ART groups, due to the potentially complex hereditary background, adverse childhood experiences and losses.

Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile X syndrome.

Fragile X syndrome (FXS), the most common inherited intellectual disability syndrome, is caused by expansion and hypermethylation of the CGG repeat in the 5' UTR of the FMR1 gene. This expanded repeat, also known as the rare fragile site FRAXA, causes X chromosome fragility in cultured cells from patients but only when induced by perturbing pyrimidine synthesis. We performed preimplantation genetic diagnosis (PGD) on 595 blastomeres biopsied from 442 cleavage stage embryos at risk for FXS using short tandem repeat (STR) markers.

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.

In vitro screening of embryos by whole-genome sequencing: now, in the future or never?

Study Question: What are the analytical and clinical validity and the clinical utility of in vitro screening of embryos by whole-genome sequencing?

Summary Answer: At present there are still many limitations in terms of analytical and clinical validity and utility and many ethical questions remain.

What Is Known Already: Whole-genome sequencing of IVF/ICSI embryos is technically possible. Many loss-of-function mutations exist in the general population without serious effects on the phenotype of the individual.

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.

Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections.

BACKGROUND Huntington's disease (HD) is an autosomal dominant neurodegenerative late onset disorder. This review of reproductive options aims to increase reproductive confidence and to prevent suffering in relation to family planning around HD and possibly other late onset neurodegenerative disorders. METHODS Selected relevant literature and own views and experiences as clinical geneticists, psychologists and ethicists have been used.

Human trophectoderm cells are not yet committed.

Study Question: Are human trophectoderm (TE) cells committed or still able to develop into inner cell mass (ICM) cells?

Summary Answer: Human full blastocyst TE cells still have the capacity to develop into ICM cells expressing the pluripotency marker NANOG, thus they are not yet committed.

What Is Known Already: Human Day 5 full blastocyst TE cells express the pluripotency markers POU5F1, SOX2 and SALL4 as well as the TE markers HLA-G and KRT18 but not yet CDX2, therefore their developmental direction may not yet be definite.

Study Design, Size, Duration: The potency of human blastocyst TE cells was investigated by determining their in vitro capacity to develop into a blastocyst with ICM cells expressing NANOG; TE cells were isolated either by aspiration under visual control or after labeling with fluorescent 594-wheat germ agglutinin.

Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres.

This study provides an overview of 13 years of experience of preimplantation genetic diagnosis (PGD) for Huntington's disease (HD) at three European PGD centres in Brussels, Maastricht and Strasbourg. Information on all 331 PGD intakes for HD, couples' reproductive history, PGD approach, treatment cycles and outcomes between 1995 and 2008 were collected prospectively. Of 331 couples for intake, 68% requested direct testing and 32% exclusion testing (with a preponderance of French couples).

Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles.

Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997-2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers.

Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD.

Background: Outcome data on children born after assisted reproduction treatments are important for both patients and health-care providers. The objective of this study was to determine whether embryo biopsy as performed in PGD has an impact on the health of infants up to 2 months of age.

Methods: A prospective comparative follow-up study of children born after PGD and children born after ICSI by collecting written reports and performing a physical examination at 2 months was performed.

Pregnancy outcome in carriers of Robertsonian translocations.

Robertsonian translocation carriers are at increased risk for infertility, spontaneous abortions, or chromosomally unbalanced offspring. Reproductive counseling of these carriers is challenging. We performed a retrospective analysis of all prenatal diagnoses from Robertsonian translocation carriers during the time period January 1, 1992 through December 31, 2007.

Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm.

Background: Safety concerns have been expressed regarding the use of immature non-ejaculated spermatozoa for ICSI. Therefore, adverse health outcomes, birth parameters, major anomaly rates and chromosomal aberrations in children born after ICSI using testicular and epididymal sperm were investigated.

Methods: Questionnaire data and results of physical examinations of 530 children born after ICSI with testicular sperm and of 194 children born after ICSI with epididymal sperm were compared with data on 2516 ICSI children born using ejaculated sperm.

Closed blastocyst vitrification of biopsied embryos: evaluation of 100 consecutive warming cycles.

Background: The aim of this study was to analyse the outcome of closed blastocyst vitrification of embryos biopsied at the cleavage stage.

Methods: Vitrification of supernumerary blastocysts was performed using the closed CBS-VIT High Security straws. Warming cycles (n = 100) for patients with preimplantation genetic diagnosis (PGD) and/or aneuploidy screening in the fresh cycle were analysed.

Mutation analysis of three genes in patients with maturation arrest of spermatogenesis and couples with recurrent miscarriages.

The primary aim of this study was to gain more insight into maturation arrest of spermatogenesis (MA) and its relationship with mutations in genes essential for meiosis. The study also investigated the possibility that mutations in human meiosis genes cause a milder phenotype and that, in such cases, meiosis could potentially be completed with the production of mature germ cells having an abnormal chromosomal constitution causing miscarriage. Among 40 patients with MA, five changes were observed that also predicted alterations at the amino acid level.

Methylation of the CpG sites in the myotonic dystrophy locus does not correlate with CTG expansion size or with the congenital form of the disease.

We have studied the methylation status of the sequence 152 nucleotides upstream of the CTG repeat of the DM1 locus in patients' peripheral blood. We used the methylation-sensitive endonucleases SacII, HpaII and HhaI, followed by PCR. This allowed to correlate the methylation status of each CTG allele with its size.

No relationship between the type of pituitary suppression for IVF and chromosomal abnormality rates of blastomeres: an observational study.

Objective: To investigate whether the incidence of chromosomally abnormal blastomeres is related to the type of pituitary suppression used in ovarian stimulation.

Design: Retrospective study.

Setting: Tertiary referral center.

Derivation, culture, and characterization of VUB hESC lines.

In this report, we present the derivation and characterization of 15 hESC lines established at the Vrije Universiteit Brussel, Belgium in collaboration with the Universitair Ziekenhuis Brussel, Belgium, using surplus in vitro fertilization embryos and embryos carrying monogenic disorders donated for research. Four lines were derived from blastocyst-stage embryos presumed to be genetically normal, and 11 hESC lines were obtained from embryos shown to carry genetic mutations by preimplantation genetic diagnosis. All the lines express markers of pluripotency as determined by immunocytochemistry and RT-PCR, and formed teratomas when injected into SCID mice.

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract.

Purpose: This study aims to analyze the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD.

Methods: Prospective cohort study. The effect of trinucleotide repeat length on reproductive outcome per patient was analyzed using bivariate analysis (T-test) and multivariate analysis using Kaplan-Meier and Cox regression analysis.