Expanded carrier screening in the United States: A systematic evidence review exploring client and provider experiences.

The aim of carrier screening is to identify prospective parents at risk of having a pregnancy affected with an autosomal recessive or X-linked disorder. Though minimal guideline-based screening is available, expanded carrier screening (ECS) is quickly becoming a feasible option for the general population due to its growing availability and affordability. However, the impact of ECS on clients and providers remains relatively unexplored. We performed a systematic evidence review to identify publications describing client-, provider-, and test-related outcomes. We searched several biomedical databases for articles published between January 1, 2003 and May 31, 2021. Studies were eligible for inclusion if they described genetic counseling and/or genetic testing for carrier screening (minimal guideline-based or ECS) in a prenatal or preconception setting in the United States. Title and abstract screening were performed using the Raayan web application or customized Google Forms. Full-text review and data extraction of included articles were performed using custom Google Forms. Two researchers performed a multistep selection process independently for validation purposes. Of 5413 unique articles screened, 36 studies were included with several studies contributing to multiple outcomes. Twenty described outcomes relating to patients/clients, 10 described provider-based outcomes, and 16 described test-based outcomes. Findings suggest that client and provider perceptions of ECS and minimal guideline-based carrier screening are multifaceted. Though clients have expressed desire for ECS, clinical uptake and impact on reproductive decision-making varies. Additionally, though genetic counselors seem to be comfortable with ECS, most other reproductive care providers seem to prefer minimal guideline or ancestry-based screening due to perceived barriers, such as time needed for ECS results disclosure and follow-up, as well as the desire to have panels set by professional societies/recommendations. There are limitations within the gathered literature, leading to potential uncertainty in the generalizability of our review. We outline several recommendations for future studies, including the need to examine variant interpretation and use of next-generation sequencing.

Offering preimplantation genetic testing for monogenic disorders (PGT-M) for conditions with reduced penetrance or variants of uncertain significance: Ethical insight from U.S. laboratory genetic counselors.

Preimplantation genetic testing for monogenic disorders (PGT-M) was originally developed to identify embryos affected with serious childhood-onset disorders, but its use has recently broadened. Guidance on the use of PGT-M in the United States (U.S.) is currently limited, with no formal laws or guidelines established on its use. The goals of this study were to determine for which types of conditions U.S. laboratories currently do not offer PGT-M, to explore ethical considerations U.S. laboratory genetic counselors (GCs) take into consideration when deciding to accept or reject a PGT-M request, and to explore whether U.S. laboratory GCs believe PGT-M should be offered for conditions with reduced penetrance or for variants of uncertain significance (VUS). Qualitative analysis of semi-structured interviews with nine genetic counselors, from five different PGT-M laboratories, was conducted. Participants were required to be GCs working at a PGT-M laboratory in the U.S. and either actively counsel patients on PGT-M or determine a patient's eligibility for PGT-M. Two participants reported their separate laboratories have no limitations for allowable PGT-M testing, while the other seven participants representing three other laboratories reported having limitations. The main ethical consideration GCs reported considering when deciding to accept or reject a PGT-M request was patient autonomy, with a focus on the patient understanding risks of the testing. All participants reported believing PGT-M should be allowable for conditions with reduced penetrance and VUS, with all participants stating their respective laboratories allow for this currently. However, all participants reported a lack of sufficient guidelines and that having guidelines from a professional organization would be beneficial to their practice. In conclusion, lack of current guidelines in the United States has created discrepancies between PGT-M laboratories. PGT-M laboratory GCs support the use of PGT-M for conditions with reduced penetrance and VUS with informed consent. The need for guidelines is supported.

OB/GYN residents' training, attitudes, and comfort level regarding genetics.

PURPOSE: While the availability, utility, and complexity of genetic testing expands, limited information exists regarding obstetrician-gynecologist (OB/GYN) residents' knowledge of genetics and confidence in providing genetic services. This study examined OB/GYN residents' educational and clinical experiences with genetics during residency, personal attitudes regarding the value of genetics and its role in their practice, level of comfort with genetic counseling, and potential motivators for learning about genetics. METHODS: Eligible participants included residents currently enrolled in a CREOG-associated OB/GYN training program in the USA or Canada. A link to an anonymous 49-question RedCap survey was emailed to program coordinators in October 2017 to be forwarded to all OB/GYN residents. RESULTS: Eighty-two OB/GYN residents representing all postgraduate years of training completed the survey. Residents indicated learning about genetics through discussions with attending physicians, lectures/courses, and publications. While residents felt their attendings valued (81%) and were knowledgeable about (85%) genetics, 28% felt their attendings did not reinforce concepts that were learned in coursework. Residents valued staying informed about the field of genetics and felt providing genetic services was within their scope of practice; however, there were deficiencies in self-reported comfort level, particularly regarding hereditary cancer counseling. Residents cited accessibility of information as a top motivator to stay informed. CONCLUSIONS: Clinically relevant, accessible didactic information about genetics reinforced in the clinical setting may increase residents' level of comfort with providing genetic services.

Not just carriers: experiences of X-linked female heterozygotes.

PURPOSE: To better understand the needs and experiences of the X-linked carrier community to improve future recognition, diagnosis, and treatment by bringing X-linked carrier voices together. METHODS: An anonymous survey link was distributed to members of Remember the Girls, a non-profit organization for female (XX) carriers of X-linked conditions, through its website, Facebook group, Instagram, and Twitter. The survey was developed to gather data on XX carriers of numerous X-linked conditions. RESULTS: One hundred and fifty individuals participated in the study. The majority (81/150) of individuals learned about their carrier status by giving birth to a son diagnosed with an X-linked condition. However, over 80% (120/145) believed that they should learn this information before the age of 18. Over 80% of participants (124/148) felt that they either have or may have symptoms attributable to their X-linked condition. Yet, only 10.1% (15/148) felt that they had sufficient access to knowledgeable healthcare providers and/or medical information. Additionally, 46.7% (70/150) of participants reported that healthcare providers did not discuss reproductive options with them. Improving carrier access to medical information, research studies, new treatments, and reproductive methods was found to be the top priority. CONCLUSION: Limited information exists on X-linked carriers' risk for symptoms and there is a lack of available treatments. This study demonstrates the need for more knowledgeable healthcare providers and medical information within the X-linked carrier community.

What women want: General population perspectives and access to preconception expanded carrier screening.

OBJECTIVE: Expanded carrier screening (ECS) assesses the risk of individuals and couples of having a child affected with a set of genetic conditions. Carriers have options available to optimize pregnancy outcomes based on personal values and preferences. The greatest range of options is available prior to pregnancy, therefore professional societies recommend this screening be performed preconception. This study aimed to assess awareness of, and interest in, ECS in women preconception. Additionally, it aimed to evaluate preferences for timing and location of education and availability of ECS. METHODS: A total of 260 nulliparous women from the general population were surveyed through Qualtrics, a national market research survey platform. Data were delineated using descriptive statistics. RESULTS: Of this cohort, 43.5% reported being aware of ECS prior to the survey and 77.8% indicated interest. Those previously aware were first informed by family, friends, or independent online research. Interest was primarily driven by a desire for reassurance and to make informed decisions about future pregnancies. Interested respondents indicated a willingness to request testing from providers. Participants showed a preference for education and access from a healthcare provider in person. CONCLUSION: These findings provide insight regarding when and where to best educate and reach women prior to pregnancy about ECS to maximize pregnancy outcomes.

Recurrent Non Immune Fetal Hydrops Associated With IPEX Syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a clinical syndrome associated with mutations in FOXP3 and consequent abnormalities of T regulatory cells. Affected males typically die in infancy or early childhood from a variety of autoimmune conditions. Reports of recurrent pregnancy loss of male fetuses in these families have been accompanied by descriptions of nonimmune fetal hydrops, with or without additional fetal anomalies. Here, we report an additional family affected by IPEX with a novel mutation leading to recurrent second trimester fetal hydrops and intrauterine fetal demise with associated fetal anomalies. This report underscores how careful genetic and pathologic analysis of even midtrimester fetuses can provide important information impacting an entire family. It also further substantiates the use of broad, symptom-targeted genetic screening panels in cases of recurrent pregnancy loss even in the absence of a remarkable pedigree.

Pregnant Women's Perspectives on Expanded Carrier Screening.

Expanded carrier screening (ECS) is a relatively new carrier screening option that assesses many conditions simultaneously, as opposed to traditional ethnicity-based carrier screening for a limited number of conditions. This study aimed to explore pregnant women's perspectives on ECS, including reasons for electing or declining and anxiety associated with this decision-making. A total of 80 pregnant women were surveyed from Northwestern Medicine's Clinical Genetics Division after presenting for aneuploidy screening. Of the 80 participants, 40 elected and 40 declined ECS. Trends regarding reasons for electing or declining ECS include ethnicity, desire for genetic risk information, lack of family history, perceived likelihood of being a carrier, and perceived impact on reproductive decisions. Individuals who declined ECS seemed to prefer ethnicity-based carrier screening and believed that ECS would increase their anxiety, whereas individuals who elected ECS seemed to prefer more screening and tended to believe that ECS would reduce their anxiety. These findings provide insight on decision-making with regard to ECS and can help guide interactions that genetic counselors and other healthcare providers have with patients, including assisting patients in the decision-making process.