International perspectives on the implementation of reproductive carrier screening

Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays). Ancestry-based offers of screening are being replaced by expanded carrier screening panels with multiple genes that is independent of ancestry. This review describes screening in Australia, Cyprus, Israel, Italy, Malaysia, the Netherlands, Saudi Arabia, the United Kingdom, and the United States. It provides an insight into the enormous variability in how reproductive carrier screening is offered across the globe. This largely relates to geographical variation in carrier frequencies of genetic conditions and local health care, financial, cultural, and religious factors.     

Gene therapy for cystic fibrosis: Will it affect the uptake of prenatal carrier screening?

We report a study which examined whether the decision of 135 couples to accept prenatal cystic fibrosis (CF) carrier screening would be influenced by the advent of gene therapy. A majority (91 couples; 67 per cent) felt that gene therapy for CF would not influence their decision to be screened. Twenty-two couples (16 per cent) stated that they would decline to be screened and an equal number felt ambivalent. Even if the life expectancy of a CF sufferer were increased by gene therapy to normal, 78 per cent of couples would still wish to avail themselves of prenatal carrier screening. A majority of women who decline screening do so because they are opposed to termination of pregnancy. The availability of gene therapy could increase the proportion of couples who accept screening.     

Defining core outcomes of reproductive genetic carrier screening: A Delphi survey of Australian and New Zealand stakeholders

Objective

Understanding the value, benefits and harms of health interventions is needed to inform best practice and ensure responsible implementation of new approaches to patient care. Such value is demonstrated through the assessment of outcomes; however, which outcomes are assessed is often highly varied across studies and can hinder the ability to draw robust conclusions. The Core Outcome Development for Carrier Screening study aims to understand the outcomes that can meaningfully capture the value of reproductive genetic carrier screening (RGCS).

Method

The authors report an iterative, two-round online Delphi survey of Australian and New Zealand stakeholders to determine the degree of consensus regarding the core outcomes of RGCS. Panellists ranked 83 outcomes according to their perceived importance on a nine-point Likert scale. Using the distribution of rankings, outcomes were grouped into tiers representative of their perceived level of importance and agreement between groups.

Results

The top tier outcomes represent those agreed to be critically important for all future studies of RGCS to assess and were used to define a preliminary core outcome set encompassing the domains (1) primary laboratory outcomes, (2) pregnancy outcomes, (3) resource use and, (4) perceived utility of RGCS.

Conclusion

These findings can guide the selection of meaningful outcomes in studies aiming to demonstrate the value of RGCS. A future international consensus process will expand on these findings and guide the inclusion of diverse perspectives across the range of settings in which RGCS is offered.     

Expanded carrier screening: What conditions should we screen for?

Carrier screening tests reproductive couples for their risk of having children affected by serious monogenic conditions. Carrier screening has historically been offered for certain conditions in high-risk populations. However, more recent evidence has shown that offering carrier screening to all patients, regardless of their ethnicity, more effectively and equitably identifies at-risk couples. Coupled with technology that enables screening for a nearly unlimited number of conditions, this expanded carrier screening (ECS) approach is now supported by professional society guidelines. Despite recent recommendations by the American College of Medical Genetics and Genomics to screen all patients who are pregnant or considering pregnancy for 113 conditions, questions remain about what conditions should be included on a core ECS panel. Here, we briefly review the history of carrier screening and guidelines on criteria for panel design. We then suggest which of these criteria are most critical, as well as thresholds to identify which conditions meet these criteria. Based on these interpretations, we recommend a core panel of 64 conditions that would identify the vast majority of at-risk couples. Widespread adoption of a core panel such as this would result in a marked improvement in the number of patients currently receiving comprehensive carrier screening.     

Variation in uptake of serum screening: the role of service delivery

The present study aimed to determine the extent to which variation in the uptake of serum screening for Down syndrome reflects variation in the way the test is offered. A higher uptake of serum screening was seen at hospitals that offered the blood test as part of a routine visit than at those where screening required a separate visit. The type of screening test offered and whether a reminder was sent were not associated with uptake. Given the consensus that undergoing screening should be the result of an informed choice, further research is needed to determine which methods of offering serum screening facilitate and which impede informed choice. Copyright © 2002 John Wiley & Sons, Ltd.     

Informed consent for expanded carrier screening: Past,present, and future

History, law, bioethics, and geocultural influences all have impacted the modern application of informed consent. It is a complex, multilayered process to communicate information and obtain voluntary patient permission before a health care intervention. Lack of provider education about genetic disorders, complexities of advanced genomic technologies, limited time during patient encounters, and low health literacy within a population all represent challenges to effective communication. There is no consensus on how informed consent in reproductive genetics is optimally obtained. Expanded carrier screening (ECS) is purposed to simultaneously test for a large list of diseases in a pan-ethnic manner. The increased use of ECS is driven by advances in genomic technologies, decreased cost, an improved understanding of single gene disorders, and in support of reproductive autonomy. Academic organizations recommend pretest counseling when patients consider ECS, yet best practice is not established. Ongoing research is needed to determine how optimally implement informed consent given the increased complexity of ECS.     

Asymptomatic carrier of two CFTR mutations: Consequences for prenatal diagnosis?

The cystic fibrosis (CF) gene has been observed to have the highest frequency of mutations in the Caucasian population. Prenatal diagnosis can now be performed with a high degree of accuracy since the identification of most of the gene's mutations, as well as the characterization of intragenic markers. However, the observation of a distribution of clinical phenotypes increases the need to identify a mild phenotype and avoid false-negative diagnosis. By screening most of the exons of the CFTR gene, we showed that a supposed obligate carrier of CF was in fact an asymptomatic affected woman.     

Prenatal cystic fibrosis carrier screening: Factors in a woman's decision to decline testing

Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.     

双酚A类似物的雄性生殖毒性研究进展

聚焦BPA类似物对雄性动物的生殖毒性研究,分析双酚S、双酚F、双酚AF、双酚B和双酚E对哺乳类实验动物睾丸及组织结构、附睾重量及组织学结构、激素水平、精子参数等常规指标的影响,考察关于鱼类和两栖类动物的研究.研究发现,不管暴露剂量高低、暴露方式的差异或是动物种属的不同,所有BPA类似物的暴露都显示阳性结果,这与BPA雄性生殖毒性尚有争议的事实形成对比,暗示这些BPA类似物具有比BPA更明显的雄性生殖毒性.总体来看,目前的BPA类似物雄性生殖毒性的数据只局限在有限的几个实验室,且实验的质量控制难以评价.因此,BPA类似物的雄性生殖毒性的数据还需要更多实验室的验证,并且过程中需要严格控制动物实验的质量,以获得更加可靠且可重复的结果.