Pregnancy-related issues in rare and low-prevalence diseases: results of ERN transversal working group on pregnancy and family planning survey.

Background: Rare and complex diseases can have a significant impact on family life, and managing the reproductive aspects of patients of childbearing age with rare diseases is often difficult and complex. A European Reference Network (ERN) Transversal Working Group (WG) on Pregnancy and Family Planning was created to join forces to promote and address issues on these topics in rare and low-prevalence diseases.

Objective: To outline the challenges and the good practices related to pregnancy and family planning in rare and complex diseases for healthcare professionals (HCPs).

Preconception carrier screening in couples seeking IVF: exploring the patient perspective.

Research Question: What is the level of understanding, and what are the attitudes and considerations regarding preconception carrier screening (PCS) among couples seeking IVF or intracytoplasmic sperm injection (ICSI)?

Design: A mixed-methods design was used. Nine interviews were conducted with couples or individual partners (n = 16) who had an initial consultation for IVF/ICSI in the 2 years preceding this study. A questionnaire was completed by 115 participants.

Fetal Presentation of MYRF-Related Cardiac Urogenital Syndrome: An Emerging and Challenging Prenatal Diagnosis.

Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.

Reproductive options and genetic testing for patients with an inherited cardiac disease.

In the past decade, genetic testing for cardiac disease has become part of routine clinical care. A genetic diagnosis provides the possibility to clarify risk for relatives. For family planning, a genetic diagnosis provides reproductive options, including prenatal diagnosis and preimplantation genetic testing, that can prevent an affected parent from having a child with the genetic predisposition.

Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing.

High-throughput sequencing technologies have increasingly led to discovery of disease-causing genetic variants, primarily in postnatal multi-cell DNA samples. However, applying these technologies to preimplantation genetic testing (PGT) in nuclear or mitochondrial DNA from single or few-cells biopsied from in vitro fertilised (IVF) embryos is challenging. PGT aims to select IVF embryos without genetic abnormalities.

Prenatal cell-free DNA testing of women with pregnancy-associated cancer: a retrospective cross-sectional study.

Background: Incidentally, the non-invasive prenatal test (NIPT) shows chromosomal aberrations suspicious of a maternal malignancy, especially after genome-wide testing. The aim of this study is to determine how many cases of cancer in pregnancy are diagnosed or missed with NIPT and whether in retrospect subtle changes in NIPT results could have detected cancer.

Methods: We identified Dutch patients diagnosed in 2017-2021 with pregnancy-associated cancer from the International Network on Cancer, Infertility and Pregnancy (INCIP) Registry, who underwent NIPT in the Dutch NIPT implementation study (TRIDENT-2).

Comprehensive Recommendations for the Clinical Management of Pregnant Women With Noninvasive Prenatal Test Results Suspicious of a Maternal Malignancy.

In this article, we defined comprehensive recommendations for the clinical follow-up of pregnant women with a malignancy-suspicious NIPT result, on the basis of the vast experience with population-based NIPT screening programs in two European countries complemented with published large data sets. These recommendations provide a tool for classifying NIPT results as malignancy-suspicious, and guide health care professionals in structured clinical decision making for the diagnostic process of pregnant women who receive such a malignancy-suspicious NIPT result.

Clinical Guideline for Preimplantation Genetic Testing in Inherited Cardiac Diseases.

Background: Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) genetic variants. PGT has been applied in inherited cardiac disease and is included in the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have the strongest risk reduction most from PGT are lacking.

Considerations of breast cancer survivors to return for embryo transfer after fertility preservation: A qualitative study.

Objective: To gain insight into the considerations of breast cancer survivors to return or not for embryo transfer after the use of fertility preservation.

Study Design: This is a qualitative study with semi-structured interviews. The interviews were planned until saturation of themes had been achieved.

Preimplantation genetic testing for Neurofibromatosis type 1: more than 20 years of clinical experience.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects the skin and the nervous system. The condition is completely penetrant with extreme clinical variability, resulting in unpredictable manifestations in affected offspring, complicating reproductive decision-making. One of the reproductive options to prevent the birth of affected offspring is preimplantation genetic testing (PGT).

Consanguineous couples' experiences and views regarding expanded carrier screening: Barriers and facilitators in the decision-making process.

Expanded carrier screening (ECS) entails a screening offer for multiple recessive disorders at the same time, and allows testing of individuals or couples regardless of ancestry or geographic origin. Children of consanguineous couples have a higher-than-average risk of manifesting autosomal recessive disorders. This study aims to contribute to the responsible implementation of ECS for consanguineous couples.

[Couples with risk of a child with a mitochondrial disease: wat are the reproductive options?].

Mitochondrial diseases are the most common inborn errors of metabolism. These severe multisystem disorders cause serious morbidity and mortality. Generally no treatment is available.

Embryo tracking system for high-throughput sequencing-based preimplantation genetic testing.

Study Question: Can the embryo tracking system (ETS) increase safety, efficacy and scalability of massively parallel sequencing-based preimplantation genetic testing (PGT)?

Summary Answer: Applying ETS-PGT, the chance of sample switching is decreased, while scalability and efficacy could easily be increased substantially.

What Is Known Already: Although state-of-the-art sequencing-based PGT methods made a paradigm shift in PGT, they still require labor intensive library preparation steps that makes PGT cost prohibitive and poses risks of human errors. To increase the quality assurance, efficiency, robustness and throughput of the sequencing-based assays, barcoded DNA fragments have been used in several aspects of next-generation sequencing (NGS) approach.

The effects of an online decision aid to support the reproductive decision-making process of genetically at risk couples-A pilot study.

Couples at risk of transmitting a genetic disease to their offspring may experience doubts about their reproductive options. This study examines the effects of an online decision aid (DA) on the (joint) reproductive decision-making process of couples (not pregnant at time of inclusion) at risk of transmitting a genetic disease to their offspring. The primary outcome is decisional conflict, and secondary outcomes are knowledge, realistic expectations, deliberation, joint informed decision-making, and decisional self-efficacy.

Liquid biopsy: state of reproductive medicine and beyond.

Liquid biopsy is the process of sampling and analyzing body fluids, which enables non-invasive monitoring of complex biological systems in vivo. Liquid biopsy has myriad applications in health and disease as a wide variety of components, ranging from circulating cells to cell-free nucleic acid molecules, can be analyzed. Here, we review different components of liquid biopsy, survey state-of-the-art, non-invasive methods for detecting those components, demonstrate their clinical applications and discuss ethical considerations.

Facioscapulohumeral muscular dystrophy-Reproductive counseling, pregnancy, and delivery in a complex multigenetic disease.

Reproductive counseling in facioscapulohumeral muscular dystrophy (FSHD) can be challenging due to the complexity of its underlying genetic mechanisms and due to incomplete penetrance of the disease. Full understanding of the genetic causes and potential inheritance patterns of both distinct FSHD types is essential: FSHD1 is an autosomal dominantly inherited repeat disorder, whereas FSHD2 is a digenic disorder. This has become even more relevant now that prenatal diagnosis and preimplantation genetic diagnosis options are available for FSHD1.

To what extent do decision aids for prenatal screening and diagnosis address involvement of partners in decision-making? - An environmental scan.

Objective: Numerous decision aids (DAs) have been developed to inform pregnant people about prenatal screening as the decision whether or not to accept the prenatal screening offer may be difficult. Currently, little is known about the role of the decisional partner of the pregnant people in this decision-making process and to what extent DAs involve and engage the partner.

Methods: A broad search was conducted to identify publicly available DAs in English and/or Dutch regarding prenatal screening and diagnosis.

Disease Onset in Huntington's Disease: When Is the Conversion?

Background: Determination of disease onset in Huntington's disease is made by clinical experience. The diagnostic confidence level is an assessment regarding the certainty about the clinical diagnosis based on motor signs. A level of 4 means the rater has ≥99% confidence motor abnormalities are unequivocal signs of disease.

Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice.

Purpose: Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care.

Hereditary diseases and child wish: exploring motives, considerations, and the (joint) decision-making process of genetically at-risk couples.

Couples who are at risk of transmitting a genetic disease to their offspring may face difficult challenges regarding reproductive decision-making. Deciding if, and how, to purse their child wish can be a demanding process. This study aims to describe the reproductive joint decision-making process of genetically at-risk couples.

Surgical management for isolated macrodactyly in an adult PIK3CA mutant.

Isolated macrodactyly in adults caused by mosaic pattern PIK3CA mutation can result in significant functional impairment and psychological burden. Due to the rarity of this condition there are no clear treatment guidelines, and those few available are focused on paediatric cases. Reports on surgical management of isolated macrodactyly in adults are lacking.

Reproductive decision-making in the context of hereditary cancer: the effects of an online decision aid on informed decision-making.

Individuals having a genetic predisposition to cancer and their partners face challenging decisions regarding their wish to have children. This study aimed to determine the effects of an online decision aid to support couples in making an informed decision regarding their reproductive options. A nationwide pretest-posttest study was conducted in the Netherlands among 131 participants between November 2016 and May 2018.

Preimplantation Genetic Testing for Monogenic Kidney Disease.

Background And Objectives: A genetic cause can be identified for an increasing number of pediatric and adult-onset kidney diseases. Preimplantation genetic testing (formerly known as preimplantation genetic diagnostics) is a reproductive technology that helps prospective parents to prevent passing on (a) disease-causing mutation(s) to their offspring. Here, we provide a clinical overview of 25 years of preimplantation genetic testing for monogenic kidney disease in The Netherlands.

Motives and considerations regarding PGT in couples carrying a structural chromosomal abnormality: a qualitative exploration.

Purpose: This study aims to describe the motives and considerations of couples carrying a structural chromosomal abnormality deciding on preimplantation genetic testing (PGT).

Methods: A qualitative exploratory study was conducted using semi-structured dyadic interviews with 13 couples (N = 26) carrying a structural chromosomal abnormality. All couples had an informative consultation in our PGT centre in the Netherlands.