Patients' choices and opinions on chorionic villous sampling and non-invasive alternatives for prenatal testing following preimplantation genetic testing for hereditary disorders: A cross-sectional questionnaire study.

OBJECTIVE: The aim of this study was to investigate choices of and reasoning behind chorionic villous sampling and opinions on non-invasive prenatal testing among women and men achieving pregnancy following preimplantation genetic testing (PGT) for hereditary disorders. METHODS: A questionnaire was electronically submitted to patients who had achieved a clinical pregnancy following PGT at the Center for Preimplantation Genetic Testing, Aalborg University Hospital, Denmark, between 2017 and 2020. RESULTS: Chorionic villous sampling was declined by approximately half of the patients. The primary reason for declining was the perceived risk of miscarriage due to the procedure. Nine out of 10 patients responded that they would have opted for a non-invasive prenatal test if it had been offered. Some patients were not aware that the nuchal translucency scan offered to all pregnant women in the early second trimester only rarely provides information on the hereditary disorder for which PGT was performed. CONCLUSION: Improved counseling on the array of prenatal tests and screenings available might be required to assist patients in making better informed decisions regarding prenatal testing. Non-invasive prenatal testing is welcomed by the patients and will likely increase the number of patients opting for confirmatory prenatal testing following PGT for hereditary disorders.

Impact of introduction of noninvasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.

OBJECTIVE: To evaluate the impact of introduction of noninvasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies. METHODS: Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Cases were segregated according to whether they were seen prior to introduction of NIPT (group A, 2010-2013) or thereafter (group B, 2014-2017). We examined the rate of invasive and noninvasive genetic testing in each group. RESULTS: We retrieved 500 cases: 308 (62%) were isolated CNS anomalies, and 192 (38%) had additional structural anomalies. In the total cohort, 165 women (33%) underwent expectant management with no further prenatal genetic testing, 166 (33%) had invasive testing, 52 (10%) had NIPT, and 117 pregnancies (23%) were terminated without further prenatal investigations. The introduction of NIPT significantly decreased the number of pregnancies having no testing (44% group A vs 22% in group B, p < .0001), particularly in the group presenting with isolated ventriculomegaly, but did not affect the uptake of invasive testing (34% vs 32%, respectively; p = .61). NIPT would have missed 4% of pathogenic copy number variants (CNVs) in the group of cases with isolated brain anomalies and 11% of CNVs in cases with complex anomalies. CONCLUSIONS: Uptake of invasive prenatal testing in fetuses with brain anomalies was not affected by NIPT. However, the incidence of no genetic testing was significantly reduced. NIPT was a suboptimal testing strategy in this population as it missed a significant number of subchromosomal genetic anomalies.

Trait anxiety, information modality, and responses to communications about prenatal genetic testing.

Decisions to undergo invasive prenatal diagnostic procedures can be anxiety provoking. Individuals receive information about these procedures in one of three modalities: written text, audio (verbal description), or video. We examined whether modality influences emotional responses and testing decisions, and whether trait anxiety, a disposition linked with heightened sensitivity to threatening information, moderates these effects. New Zealand adults (N = 176) completed a trait anxiety measure before random allocation to view a text, audio, or video message about amniocentesis and chorionic villus sampling. Participants completed measures of child related worry, anticipated emotional distress, anticipated coping efficacy, perceived likelihood of miscarriage, and testing interest. High-anxious individuals reported greater distress and lower coping efficacy in response to the video message compared to the audio message. They also reported greater miscarriage likelihood in response to the video message compared to the text message. These findings suggest that use of video, assumed to be most informative for educating patients, could induce greater distress about prenatal testing in individuals prone to anxiety.

Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?

OBJECTIVES: To present the current status of the prenatal diagnosis services and results from the largest thalassaemia center in Egypt treating 3000 patients. Traditionally, prenatal diagnosis has not been successful in reducing the births of affected children in Egypt, because the majority of women undergoing prenatal diagnosis continued to have affected pregnancies. METHODS: Seventy-one pregnant mothers at risk for ß-thalassaemia underwent prenatal diagnosis by chorionic villus sampling (n=57) or amniocentesis (n=14) between 11 to 14 weeks of gestation. Molecular characterization of fetal DNA by reverse dot blot hybridization and polymerase chain reaction-amplification refractory mutation system techniques was conducted in all cases. RESULTS: Twenty-four women (33.8%) were found to have affected fetuses; 100% of these women opted to terminate the pregnancy. The change in attitude towards termination of pregnancy was related to in-depth counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy. Forty-eight women (66.2%) with normal or carrier fetuses for ß-thal requested human leukocyte antigen typing of the fetal material to determine if the fetus was a human leukocyte antigen match for their existing thalassaemic siblings. CONCLUSION: This study demonstrates that prenatal diagnosis is feasible and acceptable in Egypt, a Muslim country, provided an in-depth discussion, which also addresses the religious considerations of prevention, is held with the couples.

Maternal anxiety and pain during prenatal diagnostic techniques: a prospective study.

OBJECTIVE: To explore anxiety and pain felt by women undergoing chorionic villus sampling (CVS) and amniocentesis (AC). METHOD: We prospectively questioned 254 women (67 undergoing CVS, 187 AC) before the procedure on their anxiety, after the procedure on their pain felt, and the support they received or desired. The medical team collected technical information concerning each procedure. RESULTS: The level of anxiety was significantly higher in women undergoing CVS than AC, in those who had received complete information before the procedure, and when indication for the procedure was fetal structural abnormalities. The level of pain was significantly higher in cases of anxious women, those undergoing a CVS rather than AC, those who had undergone invasive prenatal diagnostic procedures in previous pregnancies, in procedures deemed difficult by the operator, and with needle insertion in the lateral part of the uterus. About 30% of women undergoing CVS and 8% of those undergoing AC would have desired some form of pain prevention, mostly with nonpharmacologic therapy. CONCLUSION: Prenatal diagnosis is frequently associated with anxiety and pain. We identified factors that could exacerbate either one. When questioned, patients would desire a nonpharmacologic means for pain prevention.

Clinical correlates of pain and anxiety in prenatal diagnostic procedures.

OBJECTIVE: To study patient perception of pain and anxiety before and after amniocentesis (AC) and transabdominal chorionic villus sampling (CVS) and the clinical correlates of pain and anxiety. METHODS: 92 women underwent AC and 78 CVS. Visual analog scale was used to quantify pain and anxiety, immediately before and after the procedure. Factors which could affect pain and anxiety were noted. RESULTS: The pain and anxiety anticipated before the procedures were significantly less than actually perceived. The pre-procedure anxiety did not correlate with post-procedure pain. There was no correlation between anticipated pain or anxiety and age, parity, education, socioeconomic status, and history of procedure in previous pregnancy in both the AC and CVS groups. Post-procedure pain did not correlate with age, parity, education, socioeconomic status, abdominal scar, placental location, number of needle insertion, repeat procedure or abdominal wall thickness in either group. However, on multiple linear regression the overall post-procedure pain was associated with the number of needle insertions. CONCLUSION: Though pre-procedure pain and anxiety levels are high, most patient experience less pain and anxiety after the procedure.

Beyond the first trimester screen: can we predict who will choose invasive testing?

PURPOSE: The purpose of this study is to determine what factors, in addition to a positive first trimester aneuploidy screen, correlate with a pregnant patient's decision to undergo invasive prenatal testing. METHODS: We conducted a retrospective cohort study of singleton pregnancies referred to the Johns Hopkins Prenatal Diagnosis and Treatment Center between 2001 and 2009 with an indication of positive first trimester screen. We compared demographic factors and numerical first trimester screen results with invasive testing uptake. Risk difference calculations and linear modeling were used for analysis. RESULTS: A total of 171 eligible patients were identified. Maternal age, race, residual risk, marital status, and year of first trimester screen correlated significantly with invasive testing uptake. Family history was predictive of invasive testing uptake for patients younger than 35 years only. Type of elevated risk (trisomy 21 vs. 18 and 13), assisted reproductive technology status, parity, and increase from age-related risk were not predictive. A general linear model for relative risk with Gaussian error showed significant interaction between the variables of age and family history, so the two traits were analyzed separately (P = 0.009). CONCLUSIONS: Among patients with positive first trimester screen results, several demographic traits are predictive of invasive testing uptake. This information can help providers to identify patients at increased risk of declining invasive testing and can help providers anticipate educational needs. Further investigation should be conducted to elucidate the causes of these differences, which may relate to misinformation about the testing options and differences in values systems.

Different communication strategies for disclosing results of diagnostic prenatal testing.

BACKGROUND: Any screening program aiming to reassure pregnant women that their unborn baby is healthy will cause anxiety while waiting for the test results. OBJECTIVES: 1) To determine if revealing amniocentesis or chorionic villous sampling (CVS) results on a fixed date alters maternal anxiety during the waiting period, compared with a policy of revealing the result "when available" (i.e. variable date). 2) To evaluate whether issuing early results from a rapid molecular test alters maternal anxiety during the waiting period. 3) To evaluate whether different methods of communication (telephone, fax, email, face to face) have any impact on the parents' satisfaction and anxiety levels. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2010). SELECTION CRITERIA: All published and unpublished randomised trials, in which methods of issuing prenatal test results are compared. DATA COLLECTION AND ANALYSIS: Two review authors (Faris Mujezinovic and Zarko Alfirevic) assessed eligibility and trial quality and performed data extraction. MAIN RESULTS: Two studies (involving 286 women) from amniocentesis (but none from CVS) compared the impact of communicating results of rapid testing with waiting for definitive karyotype. Unfortunately, it was not possible to perform pooled analysis because one study reported only median (interquartile range) data, presumably because the data were not normally distributed.One study reported a statistically significant reduction in the average anxiety during the waiting period for women who had had a rapid test compared with those who had not (mean difference (MD) -2.30, 95% confidence intervals (CI) -3.08 to - 1.52). The other study compared median (interquartile range) for the trait- and state-anxiety scores and found no difference between the two groups. AUTHORS' CONCLUSIONS: We found no conclusive evidence that, while waiting for the full karyotype following amniocentesis, issuing results from a rapid analysis reduces maternal anxiety. The limited evidence from the two trials included in this review does not help resolve the dilemma about whether full karyotyping should be abandoned in favour of limited rapid testing for women undergoing Down's syndrome screening. This choice will rest on clinical arguments and cost-effectiveness rather than impact on anxiety.There is also no evidence to support the view that issuing amniocentesis results as soon as they are available is more user friendly than using a pre-defined fixed date. Studies evaluating the effect of different strategies for disclosing results on women anxiety for CVS are needed.

Knowledge and attitudes towards prenatal diagnostic procedures among pregnant women in Greece.

OBJECTIVE: To assess knowledge and attitudes towards prenatal diagnostic procedures among pregnant women living in Greece who underwent amniocentesis or chorionic villus sampling in relation to underlying demographic, lifestyle and medical history predictors. METHOD: 354 women, upon receiving the results, were interviewed in person. A structured questionnaire was answered based upon sociodemographic, educational, lifestyle and medical history variables, as well as questions pertaining to the women's knowledge, use and opinion of prenatal tests. Summary statistics and multiple logistic regression analyses were performed. RESULTS: No prior information on prenatal diagnostic procedures was reported in 29% or on prenatal screening tests in 50% of the study subjects. Women with no history of inherited diseases were about threefold more likely to have inadequate knowledge (OR = 2.72, p = 0.01) as were women of non-Greek nationality (OR = 3.27, p = 0.02) as well as those who reported being unaware of the health consequences of smoking during pregnancy (OR = 2.50, p = 0.005). By contrast, women of higher education were over twofold more likely to attain a higher level of knowledge of prenatal diagnostic procedures (OR = 0.51, p = 10(-4)) as were those reported reading the popular press (OR = 0.44, p = 10(-4)). CONCLUSION: In spite of the increased availability of prenatal diagnosis, much more is needed to be done in order to improve the efficiency of prenatal counseling, especially in immigrants and women with a low educational background.

Chorionic villous sampling: differences in patients' perspectives according to indication, ethnic group and religion.

BACKGROUND: The decision to undergo prenatal testing may be influenced by ethnic or religious factors. OBJECTIVES: To evaluate factors that might influence the decision of pregnant women to choose chorionic villous sampling for prenatal testing. METHODS: The study group comprised 239 women referred for prenatal diagnosis who elected to undergo CVS. The data were analyzed according to indication, ethnic group and religion. RESULTS: Among women undergoing CVS because of advanced maternal age and anxiety, we noted a significantly high proportion of unbalanced families, i.e., with three or more children of the same gender and deviated gender ratio. We found a significant excess of males among the Jewish families and a significant excess of females among the non-Jewish families. Jews were over-represented in the monogenic group while Christian Arabs were over-represented in the maternal age/anxiety group. CONCLUSIONS: The proportion of women who chose CVS for prenatal diagnosis varied according to indication, ethnic group and religion. The data in this study indicate that CVS may have been utilized for balancing families with > or = 3 or more children of the same sex. Christian Arabs chose CVS more often than the other groups. Jewish women may have utilized CVS for family balancing of both sexes, while non-Jews may have utilized CVS for balancing families with > or = 3 daughters.

Acceptance of chorionic villus sampling in the southwest region of The Netherlands: a 5-year evaluation.

The acceptance of chorionic villus sampling (CVS) for monitoring pregnancies at risk for chromosomal and genetic disorders was studied from its introduction in the Centre for Clinical Genetics in Rotterdam in 1984 until 1988. Special attention was given to increasing acceptance in the group with advanced maternal age (AMA) (12.6% CVS in 1984, 52.2% CVS in 1988) and the group with a high genetic risk (HGR) (42.7% in 1984, 86.7% in 1988). The odds-growth-rate in CVS was 1.64 and 1.67 respectively, which was not significantly different. The relatively limited use of CVS at AMA is most likely determined by the fact that a considerable number of patients are referred too late in pregnancy to have the option of CVS.

Use of decision analysis to evaluate patients' choices of diagnostic prenatal test.

Women with a family history of a chromosomal or genetic abnormality must weigh several factors in choosing between amniocentesis and chorionic villus sampling. We compared the prenatal test choices of three such women with those of decision analytic models that incorporated their preferences. Patient preferences were assessed using visual linear rating scales. Threshold analysis was used to determine preference ranges, and stochastic sensitivity analysis to provide confidence levels, for each choice of test. The test choices of patients and decision analytic models agreed in one case, and disagreed in two cases. In one of the latter two cases, stochastic and threshold analyses showed the disagreement to be slight; for small shifts in preference differences for first- vs. second-trimester diagnosis, or first- vs. second-trimester therapeutic abortion, patient and decision model would have agreed. In the other, stochastic analysis showed their differences to be large; there were no thresholds for early diagnosis, or for early therapeutic abortion, that would have led to agreement between patient and model. In the two cases in which patient and decision model agreed or slightly disagreed, the patients had made their own choice of prenatal test. In the case in which patient and decision model strongly disagreed, the patient's physician had shared in the choice of test. Decision analysis can be useful in analyzing prenatal test choices based on individual preferences for pregnancy outcomes. When choices of patients and decision models do not agree, examination of the locus of decision making (patient vs. physician) may help resolve apparent differences.

A comparison of chorionic villi sampling and amniocentesis: acceptability of procedure and maternal attachment to pregnancy.

Sixty-one women with high-risk pregnancies participated in a clinical trial comparing chorionic villi sampling and amniocentesis. They were assessed initially on five background measures and maternal attachment to the fetus, then were randomly assigned to either chorionic villi sampling or an amniocentesis group. Women were further assessed for maternal attachment three times during pregnancy. During the final assessment, those who were planning future pregnancies were asked which of the two procedures they would prefer. No differences between groups were found on any of the five background measures. All 31 women who considered future pregnancies indicated a preference for chorionic villi sampling, regardless of the procedure they underwent during the study. Women receiving chorionic villi sampling reported significantly greater attachment during the second trimester than did women receiving amniocentesis, who viewed themselves as being less attached than other pregnant women during this period. The findings were interpreted as evidence for attachment suppression among women undergoing amniocentesis.

Women's decision-making in prenatal screening.

With serum screening (MS-AFP and hCG testing for Down's syndrome) women have to make several decisions in a limited time: whether to participate in the screening in the first place; then, if increased risk for fetal abnormality is detected, whether to have a diagnostic test, and finally, what to do if fetal abnormality is detected. The aim of this study was to examine how women themselves in an unselected population describe their decision-making in the different phases of serum screening. Women receiving a positive result from serum screening in two Finnish towns from September 1993 to March 1994 and a group of individually matched controls were invited to semistructured interviews; 45 index and 46 control women (79% of those invited) participated between their 29th and 37th weeks of gestation (mean 31 weeks). Although serum screening was most often presented as voluntary or as an option, half the women described participation as a routine or self-evident act; only one-fourth of the women described actively deciding about participation. After a positive screening result, women's reactions to diagnostic tests, and their intentions if disability would be detected, varied greatly. Most of the women actively decided about having diagnostic tests, but for 23% participation in diagnostic testing was called a self-evident act. Women's intentions regarding abortion varied from a firm decision to abort to a firm decision not to abort, and many remained ambivalent. Prenatal screening, which demands the making of several decisions in a limited time and is offered to all pregnant women as part of established maternity care, is not based on every participant's active decision-making and thus creates an ethical problem. This problem should receive special attention from those who develop, introduce and decide on new health care practices.

The role of physician preferences in the choice of amniocentesis or chorionic villus sampling for prenatal genetic testing.

Our objective was to determine the effect of physician preferences, as well as physician demographic, obstetric, and practice-related factors, on the choice of prenatal test made by their patients. We studied preferences for prenatal outcomes for 372 pregnant women who either chose amniocentesis (AMN) (n = 288) or chorionic villus sampling (CVS) (n = 84) for the indication of maternal age. We also studied preferences for these outcomes for the 92 physicians that referred them for testing. Preferences were assessed using written scenarios and were measured on linear rating scales. According to patients, the choice of prenatal test was made entirely or mostly by the physician in 14% of cases and was shared equally between patient and physician in 37% of cases. After adjustment for patient preferences, physician concern about spontaneous abortion of a normal fetus after CVS (odds ratio 0.71; CI, 0.48-1.05; p = 0.08), and a limb reduction (LRD) birth after CVS (odds ratio 0.85; CI, 0.68-1.05; p = 0.12), tended to decrease their patients' odds of choosing CVS, but the results were not statistically significant. No other physician preference, and no physician demographic, obstetric, or practice-related factor, influenced patient test choice. We conclude that after taking patient preferences into account, physician preferences and practice-related factors did not emerge as significant determinants of the choice of prenatal test made by their patients. It remains possible, however, that physician concern about spontaneous abortion and about LRD increase the likelihood of their patients choosing AMN over CVS.

Preimplantation genetic diagnosis as an alternative to amniocentesis and chorionic villus sampling: psychosocial and ethical aspects.

Social and ethical considerations play an increasing role in decisions about the use of diagnostic technologies. In this article expert opinions of a medical-biological and a social-ethical panel on psychosocial, ethical and social aspects of preimplantation genetic diagnosis (PGD) are discussed. PGD is a new diagnostic technology for identifying chromosomal or single gene defects, which is now available as a medical treatment in several western countries. In contrast to traditional technologies like amniocentesis and chorionic villus sampling PGD offers the possibility for diagnosis before pregnancy. The panels expected PGD to be chosen only in serious situations. IVF was considered to be a barrier for PGD but less so in more serious situations. Destruction of pre-embryos was thought more acceptable than selective abortion, but only marginally. Finally a substantial decrease was expected in the acceptance of handicapped people in society as a consequence of the possibilities of technologies like PGD. Although PGD offers new possibilities for couples at risk of having a child with a genetic defect, it is important that couples are counseled in a way that emphasizes both the advantages and disadvantages of the technology. The general public should be informed about possibilities and impossibilities of preventive diagnosis and the right of future parents not to use genetic diagnosis.

Mothers' reactions to prenatal diagnostic procedures and dexamethasone treatment of congenital adrenal hyperplasia.

A retrospective survey of mothers' attitudes toward and experiences of chorionic villus sampling, amniocentesis and dexamethasone (DEX) treatment was conducted in 38 women who underwent a prenatal diagnostic procedure for congenital adrenal hyperplasia because of a previously affected child (n = 37) or because the mother herself was affected (n = 1). Both diagnostic procedures were well tolerated and almost every woman said that the anxiety or discomfort associated with the procedure was far outweighed by the value of knowing whether or not her fetus was affected. The earlier diagnostic information provided by chorionic villus sampling was highly valued. Maternal side-effects of DEX were common (75%) and more than one-third of the women rated one or more side-effects as "severe' (weight gain, fatigue, stomach pain, irritability, facial hair growth). Many women expressed anxiety about possible short- and long-term side-effects of DEX on their unborn children and themselves but all said they would undergo DEX treatment again to prevent virilization.

[Maternal anxiety induced by prenatal diagnostic techniques: detection and management]. / Anxiété maternelle induite par les techniques de diagnostic prénatal: reconnaissance et prise en charge.

Recent improvement in the screening for chromosomal defects, in particular the widespread use of ultrasonography and maternal biochemistry, is leading to a high number of fetal invasive tests (amniocentesis or chorion villus sampling). An increased level of anxiety in the pregnant women, which may sometimes continue until the postnatal period, is believed to be due to these prenatal diagnosis procedures. Maternal anxiety originates in the doubts related to fetal integrity and pregnancy outcome after information of a positive biochemical screening or visualisation of an ultrasound marker of chromosomal abnormality. Each specialist involved in prenatal care should take special attention to this, because of at least two reasons. First, anxiety may reduce maternal well being during pregnancy. Second, because it could have deleterious effects on parent to infant relationships. Without any intention of lowering the positive aspects of prenatal diagnosis, it appears essential to consider the negative effects anxiety may have on both parents. From our own experience and the conclusion of previous reported studies, we suggest some measures to reduce the level of maternal anxiety related to prenatal diagnosis: (i) improvement in the quality and transparency of information offered to pregnant women; (ii) training and involvement in psychological and emotional care for each member in the medical team; (iii) special and systematic psychological care for the "high risk" pregnant women regarding anxious disorders.

[Women's experience of chorionic villi biopsy and its significance for the course of pregnancy. A qualitative study]. / Kvinders oplevelse af chorion villus biopsi og dens betydning for graviditetsforløbet. En kvalitativ undersøgelse.

Twenty-nine pregnant women and their families were questioned about how they experienced chorion villus biopsy in order to illustrate the significance of the test for the pregnancy. Semistructured interviews were carried out immediately after the test, one week later when the result was available and at ultrasonic scanning at the 18th-20th weeks of pregnancy, and these results form the basis for this study. One woman had a foetus with Down's syndrome. The remaining foetuses had normal chromosomes. The main interpretation of early foetal diagnosis and of a living foetus was positive. For the pregnant woman and her family, the main advantages were that the time of waiting for the result was reduced (as compared to the waiting time following amniocentesis) the psychological relief that the investigation can be performed early in pregnancy and that a possible termination could take place under full anaesthesia.

The evolving role of genetics in reproductive medicine.

As medicine has evolved over the last century, medical genetics has grown from nonexistence to one of the most visible aspects of how we understand and treat disease. This increased role of genetics within medicine will only increase in the coming years, and its role in reproductive medicine will be significant. Genetics has emerged as a primary focus of research with translational applications within reproductive medicine. The aim of this article is to outline the applications of genetics currently available, and how these technologies can provide a positive impact on patient care.