Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral Renal Agenesis.

Congenital bilateral renal agenesis has been considered a uniformly fatal condition. However, the report of using serial amnioinfusions followed by the live birth in 2012 and ongoing survival of a child with bilateral renal agenesis has generated hope, but also considerable controversy over an array of complex clinical and ethical concerns. To assess the ethical concerns associated with using serial amnioinfusions for bilateral renal agenesis, we assembled a multidisciplinary group to map the ethical issues relevant to this novel intervention. The key ethical issues identified were related to 1) potential risks and benefits, 2) clinical care compared with innovation compared with research, 3) counseling of expectant parents, 4) consent, 5) outcome measures, 6) access and justice, 7) conflicts of interest, 8) effects on clinicians, 9) effects on institutions, and 10) long-term societal implications. These ethical issues should be addressed in conjunction with systematic efforts to examine whether this intervention is safe and effective. Future work should capture the experiences of expectant parents, women who undergo serial amnioinfusions, those born with bilateral renal agenesis and their families as well as clinicians confronted with making difficult choices related to it.

Rethinking the Bioethics of Pregnancy: Time for a New Perspective?

Within the realm of bioethics, the construction of pregnancy classically has focused on principle-based ethics, essentially separating maternal and fetal interests. Respect for maternal autonomy becomes distinct from an obligation of fetal beneficence, placing practitioners in complicated ethical situations when the goals of pregnant women may be at odds with the best health interests of the fetus as defined by both professional groups and society in general. As a result, clinical care is framed by an ethical "maternal-fetal conflict," with important downstream legal and policy consequences for the well-being of pregnant women. Developments in the social sciences highlight the value of attending to the biosocial realm that a pregnant woman inhabits rather than relating to her and to her fetus as discrete entities. By understanding the needs, concerns, and context within which a woman lives, clinicians can practice an ethics of accompaniment. With a focus on an ethics of accompaniment, assumptions about the maternal moral responsibility to fetal health made by practitioners and society in general can directly affect not only clinical care, but also the way policy surrounding reproductive health is constructed and implemented.

A survey of access to trial of labor in California hospitals in 2012.

BACKGROUND: In 2010, the NIH and ACOG recommended increasing women's access to trial of labor after cesarean (TOLAC). This study explored access to TOLAC in California, change in access since 2007 and 2010, and characteristics of TOLAC and non-TOLAC hospitals. METHODS: Between November 2011 and June 2012, charge nurses at all civilian California birth hospitals were surveyed about hospitals' TOLAC availability and requirements for providers. VBAC rates were obtained from the California Office of Statewide Health Planning and Development (OSHPD). Distance between hospitals was calculated using OSHPD geocoding. RESULTS: All 243 birth hospitals that were contacted participated. In 2010, among the 56% TOLAC hospitals, the median VBAC rate among TOLAC hospitals was 10.8% (range 0-37.3%). The most cited reason for low VBAC rates was physician unwillingness to perform them, especially due to the requirement to be continually present during labor. TOLAC hospitals were more likely to be larger hospitals in urban communities with obstetrical residency training. However, there were six (11.3%) residency programs in non-TOLAC hospitals and 5 (13.5%) rural hospitals offering TOLAC. The majority of TOLAC hospitals had 24/7 anesthesia coverage and required the obstetrician to be continually present if a TOLAC patient was admitted; 17 (12.2%) allowed personnel to be 15-30 minutes away. TOLAC eligibility criteria included one prior cesarean (32.4%), spontaneous labor (52.5%), continuous fetal monitoring and intravenous access (99.3%), and epidural analgesia (19.4%). The mean distance from a non-TOLAC to a TOLAC hospital was 37 mi. with 25% of non-TOLAC hospitals more than 51 mi. from the closest TOLAC hospital. In 2012, 139 hospitals (57.2%) offered TOLAC, 16.6% fewer than in 2007. Since 2010, five hospitals started and four stopped offering TOLAC, a net gain of one hospital offering TOLAC with three more considering it. Only two hospitals cited change in ACOG guidelines as a reason for the change. CONCLUSIONS: Despite the 2010 NIH and ACOG recommendations encouraging greater access to TOLAC, 44% of California hospitals do not allow TOLAC. Of the 56% allowing TOLAC, 10.8% report fewer than 3% VBAC births. Thus, national recommendations encouraging greater access to TOLAC had a minor effect in California.

Asian immigrants to the United States are less likely to donate cryopreserved embryos for research use.

OBJECTIVE: To determine whether there are ethnic differences in the proportion of IVF patients donating excess cryopreserved embryos for use in research. DESIGN: Retrospective. SETTING: University clinic. PATIENT(S): Four hundred consecutive patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo disposition plan reported on the cryopreservation consent form (disposal, donation for research, or donation for therapeutic use). RESULT(S): Compared with Europeans or Asians born in the U.S., Asians born outside the U.S. were less likely to opt to donate excess embryos. Research donation was highly associated with interest in participation in clinical research. CONCLUSION(S): Decreased donation of excess embryos for research among Asians born outside the U.S. may relate to religious, sociocultural, language, or other undescribed factors. Targeted educational strategies may be critical to the development of a diverse pool of embryos available for research.

Cloning mice and men: prohibiting the use of iPS cells for human reproductive cloning.

The use of iPSCs and tetraploid complementation for human reproductive cloning would raise profound ethical objections. Professional standards and laws that ban human reproductive cloning by somatic cell nuclear transfer should be revised to also forbid it by other methods, such as iPSCs via tetraploid complementation.

Fertility patients' views about frozen embryo disposition: results of a multi-institutional U.S. survey.

OBJECTIVE: To describe fertility patients' preferences for disposition of cryopreserved embryos and determine factors important to these preferences. DESIGN: Cross-sectional survey conducted between June 2006 and July 2007. SETTING: Nine geographically diverse U.S. fertility clinics. PATIENT(S): 1020 fertility patients with cryopreserved embryos. INTERVENTION(S): Self-administered questionnaire. MAIN OUTCOME MEASURE(S): Likelihood of selecting each of five conventional embryo disposition options: store for reproduction, thaw and discard, donate to another couple, freeze indefinitely, and donate for research; likelihood of selecting each of two alternative options identified in previous research: placement of embryos in the woman's body at an infertile time, or a disposal ceremony; importance of each of 26 considerations to disposition decisions; and views on the embryo's moral status. RESULT(S): We found that 54% of respondents with cryopreserved embryos were very likely to use them for reproduction, 21% were very likely to donate for research, 7% or fewer were very likely to choose any other option. Respondents who ascribed high importance to concerns about the health or well-being of the embryo, fetus, or future child were more likely to thaw and discard embryos or freeze them indefinitely. CONCLUSION(S): Fertility patients frequently prefer disposition options that are not available to them or find the available options unacceptable. Restructuring and standardizing the informed consent process and ensuring availability of all disposition options may benefit patients, facilitate disposition decisions, and address problems of long-term storage.

Importing human pluripotent stem cell lines derived at another institution: tailoring review to ethical concerns.

Stem cell researchers commonly use human pluripotent stem cell lines derived by other investigators. Researchers may use lines derived elsewhere, provided that their derivation met consensus core standards. Some types of derivation raise heightened levels of ethical concern and require greater scrutiny. To maintain public trust, research institutions need to justify why they allow researchers to use lines whose derivation would not have been permitted locally.

Computerized prenatal genetic testing decision-assisting tool: a randomized controlled trial.

OBJECTIVE: Guidelines for fetal aneuploidy testing recommend that screening and diagnostic testing be made available to pregnant women of all ages and that providers explain the differences between these tests to help their patients make informed testing decisions. We sought to estimate the effect of a computerized, interactive prenatal testing decision tool on prenatal testing decision making. METHODS: Four hundred ninety-six English- or Spanish-speaking women at 20 or fewer weeks of gestation were randomly assigned to view the interactive prenatal testing decision tool or the California Department of Health Services' educational booklet. Primary outcomes were knowledge, risk awareness, intervention satisfaction, decisional conflict, and among women aged at least 35 years, use of invasive diagnostic testing. RESULTS: Women assigned to the interactive prenatal testing decision tool had higher knowledge scores (79.5% compared with 64.9%, P<.001), were more likely to correctly estimate their risk of procedure-related miscarriage (64.9% compared with 48.1%, P=.002) and carrying a Down syndrome-affected fetus (63.5% compared with 15.1%, P<.001), were more satisfied with the intervention (P<.001), and had less decision uncertainty (P<.001) than controls after viewing the intervention. Most of these differences persisted over time. Among women aged at least 35 years, the interactive prenatal testing decision tool viewers who were originally less inclined to undergo invasive testing were ultimately more likely than similarly inclined controls to have amniocentesis or chorionic villus sampling (44.8% compared with 29.2%), whereas those who were originally more inclined to undergo an invasive procedure ultimately were less likely than similarly inclined controls to have a diagnostic procedure (84.6% compared with 94.9%; P=.015 for interaction). CONCLUSION: Using an interactive prenatal testing decision tool results in more informed prenatal genetic testing decisions than viewing standard educational booklets. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00686062 LEVEL OF EVIDENCE: I.

Effect of noncancerous pelvic problems on health-related quality of life and sexual functioning.

OBJECTIVE: To assess the effect of abnormal uterine bleeding and pelvic pain and pressure on health-related quality of life and sexual functioning and assess treatment satisfaction. METHODS: This is a cross-sectional study of 1,493 sociodemographically diverse women who were seeking care for noncancerous pelvic problems and who had not undergone hysterectomy. Participants were asked about symptoms, attitudes, health-related quality of life, sexual functioning, and treatment satisfaction. Preference for current health was measured using the time tradeoff metric, which asked respondents to estimate the number of years of life they would be willing to trade off to not have a uterine condition. Multivariable logistic regression was used to identify determinants of treatment satisfaction. RESULTS: Most (82.7%) participants reported a complete lack of or only partial symptom resolution, and 42.3% reported that their pelvic problems interfered with their ability to have and enjoy sex. Mean Short Form-12 Physical (43-49) and Mental (41-44) Component Summary scores were substantially lower than population norms for women aged 40-49 years. Mean current health time tradeoff scores ranged from 0.78 to 0.88. Satisfaction with Western medicines ranged from 31.3% (progestin intrauterine device) to 58.2% (opiates) and with uterine-preserving surgery from 20.0% (dilation and curettage) to 51.0% (myomectomy); 27.7 % of the women who used acupuncture were satisfied. Participants with lower educational attainment, greater symptom resolution, and less interference of pelvic problems with sex were more likely to be satisfied. CONCLUSION: Noncancerous pelvic problems are associated with serious decrements in health-related quality of life and sexual functioning and low rates of treatment satisfaction. LEVEL OF EVIDENCE: II.

Predictors of hysterectomy in women with common pelvic problems: a uterine survival analysis.

BACKGROUND: Comprising over 600,000 patients per year, hysterectomy is the most common nonobstetrical operation performed in US women. Little is known about the natural history of the noncancerous uterine conditions leading to hysterectomy. We followed a prospective cohort of women with common pelvic problems to determine whether simple clinical characteristics could predict a subsequent hysterectomy. STUDY DESIGN: We recruited 762 women seeking care for abnormal uterine bleeding, chronic pelvic pain, or symptomatic uterine fibroids and ascertained their hysterectomy status during 4 years of surveillance. We collected baseline patient-reported sociodemographic and clinical data and fit Cox models to predict the effects of covariates on hysterectomy across patient age. RESULTS: There were 99 hysterectomies, resulting in 0.044 hysterectomies per person-year of observation and a 13.5% cumulative hysterectomy rate. Hysterectomy was independently predicted by multiple pelvic symptoms or symptomatic fibroids (hazard ratio [HR], 1.97; 95% CI, 1.18-3.28), previous use of a gonadotropin-releasing hormone agonist (HR, 2.54; 95% CI, 1.53-4.24), and an absence of symptom resolution (HR, 2.24; 95% CI, 1.46-3.44). Survival curves plotted for subgroups with combinations of these predictors showed an escalating risk of hysterectomy with each additional risk factor. Predicted hysterectomy rates ranged from 20%, if all 3 predictors were absent, to 95%, if all 3 were present. CONCLUSIONS: For women with common pelvic problems, three easily measured clinical characteristics (symptom combination, degree of resolution, and earlier use of a gonadotropin-releasing hormone agonist) predict the likelihood of subsequent hysterectomy and can be used to inform counseling about the likely success of alternative treatments.

Beyond race or ethnicity and socioeconomic status: predictors of prenatal testing for Down syndrome.

OBJECTIVE: To identify predictors of prenatal genetic testing decisions and explore whether racial or ethnic and socioeconomic differences are explained by knowledge, attitudes, and preferences. METHODS: This was a prospective cohort study of 827 English-, Spanish-, or Chinese-speaking pregnant women presenting for care by 20 weeks of gestation at 1 of 23 San Francisco Bay-area obstetrics clinics and practices. Our primary outcome measure for women aged less than 35 years was any prenatal genetic testing use compared with none, and for women aged 35 years or older, prenatal testing strategy (no testing, screening test first, straight to invasive diagnostic testing). Baseline questionnaires were completed before any prenatal test use; test use was assessed after 30 gestational weeks. RESULTS: Among women aged less than 35 years, no racial or ethnic differences in test use emerged. Multivariable analyses yielded three testing predictors: prenatal care site (P = .024), inclination to terminate pregnancy of a Down-syndrome-affected fetus (odds ratio 2.94, P = .002) and belief that modern medicine interferes too much in pregnancy (odds ratio .85, P = .036). Among women aged 35 years or older, observed racial or ethnic and socioeconomic differences in testing strategy were mediated by faith and fatalism, value of testing information, and perceived miscarriage risk. Multivariable predictors of testing strategy included these 3 mediators (P = .035, P < .001, P = .037, respectively) and health care system distrust (P = .045). A total of 29.5% of screen-positive women declined amniocentesis; 6.6% of women screening negative underwent amniocentesis. CONCLUSION: Racial or ethnic and socioeconomic differences in prenatal testing strategy are mediated by risk perception and attitudes. Screening is not the best choice for many women. Optimal prenatal testing counseling requires clarification of risks and consideration of key attitudes and preferences regarding the possible sequence of events after testing decisions.

A new era in the ethics of human embryonic stem cell research.

Scientific progress in human embryonic stem cell (hESC) research and increased funding make it imperative to look ahead to the ethical issues generated by the expected use of hESCs for transplantation. Several issues should be addressed now, even though phase I clinical trials of hESC transplantation are still in the future. To minimize the risk of hESC transplantation, donors of materials used to derive hESC lines will need to be recontacted to update their medical history and screening. Because of privacy concerns, such recontact needs to be discussed and agreed to at the time of donation, before new hESC lines are derived. Informed consent for phase I clinical trials of hESC transplantation also raises ethical concerns. In previous phase I trials of highly innovative interventions, allegations that trial participants had not really understood the risk and benefits caused delays in subsequent trials. Thus, researchers should consider what information needs to be discussed during the consent process for hESC clinical trials and how to verify that participants have a realistic understanding of the study. Lack of attention to the special ethical concerns raised by clinical trials of hESC transplantation and their implications for the derivation of new hESC lines may undermine or delay progress toward stem cell therapies.

Abortion attitudes of pregnant women in prenatal care.

OBJECTIVE: This study was undertaken to describe abortion attitudes in a diverse cohort of pregnant women enrolled in prenatal care. STUDY DESIGN: A cross-sectional interview study of 1082 demographically diverse gravid women enrolled in prenatal care at less than 20 weeks' gestation was performed. RESULTS: Most participants (92%) supported abortion availability. Half (50%) who were willing to consider an abortion would do so only in the first trimester. Among the gravid women willing to consider an abortion in the first or second trimester, 84% would do so after rape/incest or if their life was endangered and 76% would if their fetus had Down syndrome. Gravid women considering abortion were more likely to be white, older, have had a previous abortion, and to express distrust in the health care system. Women who would not consider abortion were more likely to be multiparous, married/living with partner, and to express greater faith and fatalism about their pregnancy outcome. CONCLUSION: Although most pregnant women enrolled in prenatal care support abortion availability, about half would only consider a first-trimester procedure. These findings underscore the need for early prenatal genetic counseling, screening, and testing.

Informed consent in human oocyte, embryo, and embryonic stem cell research.

Research with human oocytes, embryos, and additional embryonic stem cell lines is needed to address important scientific questions and to fulfill the promise of stem cell transplantation for degenerative diseases. Proponents need to develop guidelines for the appropriate conduct of embryonic stem cell research. Such guidelines will help build public trust and acceptance for this research. In this article, we offer recommendations for informed consent, discussing who should give consent, what the consent process should cover, when consent should be obtained, and who should obtain consent. Consent to use embryos for research should be obtained from oocyte and sperm donors as well as from the woman or couple undergoing infertility treatment. The consent discussion must cover information that donors need to know to make an informed decision about various types of research. Donations for research should be discussed at the initiation of advanced infertility treatment and reconfirmed if possible at the time of actual donation for research. Treating assisted reproduction technology physicians can help with the consent process, provided that they are not involved in the research.

How do women of diverse backgrounds value prenatal testing outcomes?

OBJECTIVES: To describe women's preferences for prenatal testing outcomes and to explore their association with sociodemographic characteristics and attitudes. METHODS: We conducted a cross-sectional study of 584 racially/ethnically and socioeconomically diverse pregnant women aged 16 to 47 years recruited from 23 San Francisco Bay Area practices. We assessed preferences for 12 potential prenatal testing outcomes using the time trade-off metric for all outcomes and the standard gamble metric for two outcomes. Preferences were calculated on a scale of 0 (death) to 1 (perfect health). Participants also completed a sociodemographic and attitude survey. RESULTS: Highest preference scores were assigned to outcomes resulting in the birth of a chromosomally normal infant (mean = 0.91-0.93; median = 0.99-1.00). Lower scores were obtained for outcomes involving pregnancy loss (mean = 0.69-0.87; median = 0.76-0.92), which were correlated with attitudes regarding miscarriage, pregnancy termination, and Down syndrome. The lowest scores were assigned to Down syndrome-affected births (mean = 0.67-0.69; median = 0.73-0.75), which also were correlated with attitudes toward Down syndrome. We did not find a statistically significant relationship between participants' preference scores and age. CONCLUSION: Preferences for prenatal testing outcomes vary according to the pregnant women's underlying attitudes about pregnancy loss and Down syndrome, and not according to her age. Current age/risk-based guidelines should account for individual variation in patient preferences.

Communicating risk in prenatal genetic testing.

Prenatal testing for Down syndrome and neural tube defects has become routine, and testing for other genetic conditions is becoming commonplace. Counseling about these tests involves a discussion of risk information, so pregnant women and their partners can use the information effectively when they make choices about testing. Discussing risk can be challenging, as many individuals, particularly those of lower literacy, have a poor understanding of the numerical concept of risk. Furthermore, whether risk is comprehended accurately or not, it is interpreted by patients in light of their existing knowledge and past experiences. Strategies available to optimize understanding of risk include communication of risk figures as frequencies rather than as probabilities or percentages and explicit discussion of a woman's preconceptions about her risk and about the condition being tested for.

Medicine. Consent from donors for embryo and stem cell research.

As research with human embryos and embryonic stem cells proceeds, the authors of this Policy Forum argue that all donors of biological materials should give informed consent, including oocyte and sperm donors. Informed consent is particularly important because of the diverse opinions and strong emotions that surround such research. Some gamete donors who are willing to help women and couples bear children may object to the use of their genetic materials for certain types of research.

Social and familial context of prenatal genetic testing decisions: are there racial/ethnic differences?

The purpose of this cross-sectional study of 999 socioeconomically and racially/ethnically diverse pregnant women was to explore prenatal genetic testing attitudes and beliefs and the role of external influences. Surveys in English, Spanish, and Chinese included questions regarding the value of testing, pregnancy, and motherhood; the acceptability of Down syndrome in the subject's community; and the role of social and cultural influences in prenatal testing decisions. We analyzed racial/ethnic differences in all attitudinal and external influence variables, controlling for age, relationship status, and socioeconomic status. We found statistically significant racial/ethnic group differences in familiarity with an individual with Down syndrome and in 10 of 12 attitude, belief, and external influence variables, even after controlling for other sociodemographic characteristics. We also observed substantial variation within racial/ethnic groups for each of these measures. Despite the statistically significant group differences observed, R(2) values for all multivariate models were modest and response distributions overlapped substantially. Social and familial contexts for prenatal testing decisions differ among racial/ethnic groups even after accounting for age, marital status, and other socioeconomic factors. However, substantial variation within groups and overlap between groups suggest that racial/ethnic differences play a small role in the social and familial context of prenatal genetic testing decisions.