• BRCA
• Hereditary breast and ovarian Cancer syndrome
• Previvors

• Humans
• Fertility Preservation/methods
• Female
• Adult
• Retrospective Studies
• Hereditary Breast and Ovarian Cancer Syndrome/genetics
• Cryopreservation
• BRCA1 Protein/genetics
• BRCA2 Protein/genetics
• Young Adult

• aortic disease
• decision‐making
• lived experience
• preimplantation genetic testing (PGT‐M)

• Humans
• Female
• Preimplantation Diagnosis/psychology
• Decision Making
• Genetic Testing
• Adult
• Male
• Vascular Diseases/psychology
• Vascular Diseases/genetics
• Aorta
• Middle Aged
• Reproduction

• MGH Institute of Health Professions

• Ethics
• Hereditary cancer
• Late-onset diseases
• Legal restrictions
• Preimplantation genetic testing

• Cancer
• Inherited cancer syndrome
• Preimplantation genetic testing
• Reproduction
• Risk

• NCI P30 CA008748 NCI NIH HHS
• P30 CA008748 NCI NIH HHS
• UL1 TR002384 NCATS NIH HHS
• UL1-TR-002384 NCATS NIH HHS
• National Cancer Institute
• National Center for Advancing Translational Sciences
• American Cancer Society

• Hereditary diffuse gastric cancer
• parenthood
• qualitative
• reproductive decision-making
• young adults

• embryo disposition
• ethics
• genetic testing
• health attitudes
• preimplantation genetic diagnosis

• Aneuploidy
• Attitudes
• Ethics or ethical issues
• Monogenic disorders
• Preimplantation genetic testing

• Environmental scan
• Literacy demand
• Patient education
• Preimplantation genetic testing
• Sickle cell disease

The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients’ lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making’ about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress’ and `uncertainty’ that patients endure as a result—apart from what decision they make—is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, ‘intraindividual’, ‘interpersonal’ and ‘situational’ factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients’ well-being during their reproductive journey.

• couples
• decision uncertainty
• distress
• genetic counseling
• health decision making
• preimplantation genetic testing
• psychology
• reproductive endocrinology and infertility

• PGD
• decision making
• ethics
• genetic counseling
• health attitudes
• knowledge
• practice
• preimplantation genetic diagnosis
• psychology
• reproductive endocrinology and infertility

• E-Cadherin (CDH1)
• Hereditary cancer
• Hereditary diffuse gastric cancer (HDGC)
• Preimplantation genetic diagnosis (PGD)
• Prenatal diagnosis (PND)
• Reproductive genetic testing

• Adult
• Aged
• Antigens, CD
• Cadherins/genetics
• Female
• Genetic Predisposition to Disease
• Genetic Testing
• Health Knowledge, Attitudes, Practice
• Humans
• Male
• Middle Aged
• Mutation
• Pregnancy
• Preimplantation Diagnosis/psychology
• Stomach Neoplasms/genetics

• 16942 Cancer Research UK

• BRCA mutation
• Preimplantation genetic diagnosis (PGD)
• acceptability
• awareness
• hereditary breast and ovarian cancer (HBOC)
• knowledge
• prenatal diagnosis (PND)

Adolescents and young adults (AYA) with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns, especially fertility. The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors. However, genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel. This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis, particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing. Other hereditary cancers are also addressed; however, less is known about the psychosocial and fertility concerns in these AYA populations. Additionally, we provide an overview of the concept of “oncofertility” - the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients - and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’ treatment planning related to reproductive health and fertility.

• Fertility
• Oncology
• Genetic counselors
• Decision-making
• Oncofertility
• Adolescent young adults
• Training
• Health professionals

Preimplantation genetic diagnosis (PGD) remains nowadays a valid alternative for couples at high-risk of having a child with a genetic disease and for women older than 37–40 years with the high risk of chromosomal aneuploidies in the embryos. However the use of PGD for high penetrance recessive, dominant and X-liked disorders occurring in early life is documented, debate exists regarding its appropriateness in lower penetrance and late-onset cancer susceptibility syndromes. The data regarding the efficacy of different molecular techniques used in PGD are still lacking. We therefore sought to assess the different molecular techniques used in PGD for detecting three most frequent BRCA1 gene mutations: 5382insC, 185delAG and C61G.

Anonymous donors of the oocytes and control healthy blood samples were extracted and analyzed in the Fertility and Reproductive Center Invicta in Gdansk. Preimplantation genetic diagnosis for the most frequent mutations: 185delAG, 5382insC, C61G in BRCA 1 gene was carried out on single, unfertilized oocytes, in metaphase of second meiotic division, not qualified to IVF. Positive mutation controls were represented by cell lines from the Coriell Institute for Medical Research: GM14090 (185delAG), GM14097 (C61G), GM13715 (5382insC).

Repeatability of the results acquired from the WGA analysis for the mutation 5382insC was 38%. The repeatability of the nested-PCR analysis in the second round of the amplification was labile for the mutation 5382insC and 185delAG and was ranged from 47% to 57%. However, the repeatability for the mutation C61G was 100%.

Our results suggest that the nested-PCR technique remains more sensitive and specific method as compared to WGA. WGA performed on the single cells did not reflect expected results. The repeatability of the WGA methodology remains questionable, and any analysis attempt does not guarantee reliable results.

Further evaluation is strongly needed to propose the most accurate molecular technique used in PGD for detecting three most frequent BRCA1 gene mutations: 5382insC, 185delAG and C61G.

• Adult
• Breast Neoplasms/genetics
• Breast Neoplasms/psychology
• Choice Behavior
• Female
• Genes, BRCA1
• Genes, BRCA2
• Genetic Predisposition to Disease/psychology
• Genetic Testing
• Humans
• Male
• Mastectomy/psychology
• Middle Aged
• Mutation
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/psychology
• Pregnancy
• Preimplantation Diagnosis/psychology
• Reproduction