Decisional conflict and the disposition of frozen embryos: implications for informed consent.

BACKGROUND: Fertility patients often struggle with decisions about disposition of embryos remaining after fertility treatment. We aimed to identify predictors and correlates of decisional conflict among patients facing these decisions. METHODS: We analyzed results from a survey of 2210 patients from nine geographically diverse US fertility clinics. The main outcome measure was decisional conflict about embryo disposition, as measured by the decisional conflict scale (DCS). RESULTS: Of 1244 respondents who returned the survey, 1005 with cryopreserved embryos and DCS scores were included in the analysis. Of the respondents, 39% reported high decisional conflict (DCS ≥ 37.5). Thoughts about future childbearing were associated with high decisional conflict: respondents who were either uncertain about whether to have a baby in the future or sure they did not want to have a baby were at higher odds of high decisional conflict than participants who desired a baby [adjusted odds ratio (aOR) = 3.93, P < 0.001 and aOR = 1.69, P = 0.04, respectively]. Also associated with high decisional conflict were being likely to have embryos thawed and discarded (aOR = 2.08, P < 0.001), donated for research (aOR = 1.66, P = 0.01) or frozen 'forever' (aOR = 1.90, P = 0.01); being likely to choose compassionate transfer if it were available (aOR = 1.65, P = 0.03); attributing high, but not full, moral status to human embryos; not having enough information; and not being satisfied with the informed consent process. CONCLUSIONS: Decisional conflict about frozen embryo disposition differs according to reproductive preferences that may vary according to stage of treatment. Informed consent for embryo disposition should be revisited periodically, with serious discussions about disposition after childbearing is complete.

Attitudes of maternal-fetal specialists concerning maternal-fetal surgery.

OBJECTIVE: We examined the attitudes of members of the Society for Maternal-Fetal Medicine regarding the clinical, scientific, ethical, and policy issues in maternal-fetal surgery. STUDY DESIGN: A 43-question survey was distributed to all members of the Society for Maternal-Fetal Medicine. Two mailings and one electronic mail reminder were sent, each with instructions to submit the survey either via US mail or the Internet. The survey included questions in six categories: physician demographic data, experience with maternal-fetal surgery, views on innovative therapies, scientific validation of currently used and proposed procedures, ethical issues, and future directions in public policy. RESULTS: Of the 1639 United States members sent questionnaires, 943 replied (response rate = 59%). Forty-seven percent had referred patients for open fetal surgery for nonlethal conditions, and 69% believed physicians were obligated to inform patients of this option. Seventy-eight percent believed that innovative therapies should be performed only under institutional review board-approved protocols. Although the majority of respondents believed that certain proposed benefits of open fetal surgery for myelomeningocele could offset the risks, the majority (56%) also indicated that the procedure has not been validated. Fifty-seven percent believed that a moratorium should be imposed on open fetal surgery for nonlethal conditions, such as myelomeningocele, until a multicenter-controlled clinical trial is completed. CONCLUSIONS: The use of maternal-fetal surgery for nonlethal conditions is highly controversial. The majority of maternal-fetal specialists we surveyed support further research before such procedures are integrated into clinical practice.

Toward the ethical evaluation and use of maternal-fetal surgery.

BACKGROUND: Important clinical, social, and ethical questions are associated with the evaluation and use of surgical approaches aimed at correcting fetal anatomic abnormalities. In particular, the expansion of maternal-fetal surgery to ameliorate nonlethal fetal conditions has intensified the need to address issues about the adequacy of technology assessment and the safety of those who undergo these novel procedures. APPROACH: After discussions at a multidisciplinary conference, we reviewed the development and current practices of maternal-fetal surgery and analyzed the relevant ethical issues concerning the use of maternal-fetal surgery for nonlethal conditions, focusing on the correction of myelomeningocele. FINDINGS: Characterizing nonvalidated maternal-fetal surgery procedures as "innovative therapy" blurs the boundaries between research and therapy and creates uncertainty about the obligations of clinicians and researchers. Further, maternal-fetal surgery raises ethical issues related to maternal risks and benefits, informed consent, distinguishing lethal from nonlethal conditions, withholding unproven treatments, entrepreneurship, and prioritization. RECOMMENDATIONS: To help ensure that maternal-fetal surgery will be studied and eventually applied in a scientifically and ethically sound manner, we offer several recommendations. First, innovation in maternal-fetal surgery should be conducted and evaluated as research. Second, women must be considered research subjects in these trials. Third, the informed consent process must ensure adequate comprehension and genuine voluntariness in those considering participation. Fourth, discriminatory and fearful attitudes toward individuals with disabilities should be addressed explicitly prior to making a decision to proceed with maternal-fetal surgery in an attempt to correct such disabilities. Fifth, maternal-fetal surgery should not be performed for cosmetic indications unless and until there is reliable evidence that maternal-fetal surgery can be performed safely and that long-term side effects on women and their offspring are minimal. Sixth, centers of excellence should be established for conducting research and providing maternal-fetal surgery. Seventh, funding for research on maternal-fetal surgery should be considered in the context of societal needs.

Maternal-fetal surgery: the fallacy of abstraction and the problem of equipoise.

When surgery is performed on pregnant women for the sake of the fetus (MFS or maternal fetal surgery). it is often discussed in terms of the fetus alone. This usage exemplifies what philosophers call the fallacy of abstraction: considering a concept as if it were separable from another concept whose meaning is essentially related to it. In light of their potential separability, research on pregnant women raises the possibility of conflicts between the interests of the woman and those of the fetus. Such research should meet the requirement of equipoise. i.e., a state of genuine uncertainty about the risks and benefits of alternative interventions or noninterventions. While illustrating the fallacy of abstraction in discussions of MFS, we review the rationale for explicit acknowledgment of the essential tie between fetus and pregnant woman. Next we examine whether it is possible to meet the requirement of equipoise in research on MFS, focusing on a fetal condition called myelomeningocele. We show how issues related to equipoise in nonpregnant populations appear also in debates regarding MFS. We also examine evidence in support of claims that the requirement of equipoise has been satisfied with respect to "the fetal patient" while considering risks and benefits to gestating women only marginally or not at all. After delineating challenges and possibilities for equipoise in MFS research, we conclude with a suggestion for avoiding the fallacy of abstraction and achieving equipoise so that research on MFS may be ethically conducted.

The ethics of aggregation and hormone replacement therapy.

The use of aggregated quality of life estimates in the formation of public policy and practice guidelines raises concerns about the moral relevance of variability in values in preferences for health care. This variability may reflect unique and deeply held beliefs that may be lost when averaged with the preferences of other individuals. Feminist moral theories which argue for attention to context and particularity underline the importance of ascertaining the extent to which differences in preferences for health states reveal information which is morally relevant to clinicians and policymakers. To facilitate these considerations, we present an empirical study of preferences for the timing and occurrence of health states associated with hormone replacement therapy (HRT). Sixteen women between the ages of 45 and 55 were enrolled in this pilot study. Their preferences regarding five health states associated with HRT (menopausal symptoms. side effects of HRT, breast cancer, myocardial infarction, and osteoporosis) were assessed in quantitative terms known as utilities. Two standard methods, the visual analog scale (VAS) and the standard gamble (SG), were used to assess utility and time preference (calculated as a discount rate). The wide variability of responses underlines the importance of tailoring health care to individual women's preferences. Policy guidelines which incorporate utility analysis must recognize the normative limitations of aggregated preferences, and the moral relevance of individual conceptions of health.

Human immunodeficiency virus and assisted reproduction: reconsidering evidence, reframing ethics.

OBJECTIVE: To review the advances in the treatment of human immunodeficiency virus (HIV) infection and revisit the medical, ethical, and legal issues surrounding infertility management in HIV-infected couples. DESIGN: Analytic review. RESULTS(S): HIV infection continues to be a serious public health and reproductive issue. However, present policies which allow for the categorical exclusion of HIV-infected individuals from infertility services should be reconsidered in light of improvements in the prognosis of infected individuals and a dramatic decrease in the risk of vertical transmission. An analysis of the ethical cogency of the arguments against the provision of services does not substantiate the exclusion of HIV-infected individuals; rather, the principle of justice requires that HIV-infected women be treated the same way as a woman who might have an increased risk of conceiving a child with a disability or a may have a decreased life expectancy due to a chronic illness such as diabetes. Ethical disagreement notwithstanding, with the precedents recently established by the Americans with Disabilities Act (ADA), discrimination based on HIV status would also likely be unlawful under most circumstances. CONCLUSIONS(S): With advances in the treatment of HIV infection, contextualized counseling and a respect for patients' decisions regarding infertility treatment should be adopted as public policy. It is neither ethically nor legally justifiable to categorically exclude individuals from infertility services on the basis of HIV infection.

Histologic diagnosis of Hirschsprung's disease. The value of concurrent hematoxylin and eosin and cholinesterase staining of rectal biopsies.

False positive and negative results can complicate the diagnosis of Hirschsprung's disease (HD) with the acetylcholinesterase (AChE) stain. To improve the diagnostic value of this test, the authors evaluated the concurrent hematoxylin and eosin (H and E) staining of extra sections after the AChE procedure. Flash-frozen (FF), cryostat-cut (CC) sections of rectal suction biopsies from 96 patients with constipation were evaluated by AChE together with H and E staining of additional unstained sections. In 13 of 15 cases of HD with a diagnostic (positive-A) AChE pattern, the H and E sections confirmed the diagnosis. In five cases with other AChE patterns, the H and E sections were instrumental when the diagnosis was made. Of the 76 non-HD subjects with positive-B (n = 8), equivocal (n = 6), and negative (n = 62) AChE patterns, the H and E sections eliminated the diagnosis in 62 (81%). Neuronal and nerve fiber morphologic characteristics were excellent. Rebiopsies were needed in 14 subjects (19%) when there was failure in finding neurons. Simplicity, quickness, and the high quality of the histologic preparations make this procedure a useful adjunct to the AChE stain.

Histochemical diagnosis of Hirschsprung disease.

A histochemical staining technique for detection of acetylcholinesterase (AChE) in rectal suction biopsies was compared with the presence or absence of ganglion cells in full-thickness or suction biopsies for the diagnosis of Hirschsprung disease (HD) in infants and children. Biopsies from 55 of 58 children were adequate for both the AChE assay and routine pathologic examination for ganglion cells. Two patterns of AChE staining were noted. With pattern A, prominent nerve fibers staining for AChE were seen throughout the muscularis mucosa and the lamina propria. With pattern B, similar fibers were seen only in the muscularis mucosa and the areas of lamina propria that were immediately adjacent. No "false-negative" AChE staining reactions were found in patients with HD. No "false-positive" reactions showing pattern A were found. This pattern was diagnostic for HD. Three false-positive reactions were found showing pattern B in patients with conditions other than HD. Among 22 patients with HD, 19 were males and three were females. Pattern A occurred in all age groups and in both sexes. Pattern B in patients with HD was seen exclusively in male infants 1 month of age or less. Experience suggests that the AChE staining of rectal suction biopsies is an excellent screening test for HD in infants and children. If pattern B is encountered, however, the specimen should be examined by routine pathologic techniques for the presence of submucosal ganglion cells.

ABO hemolytic disease in Puerto Rico and North Carolina.

A prospective study was carried out at the University of Puerto Rico Hospital (UPRH) and at the North Carolina Baptist Hospital (NCBH) in order to establish the incidence of ABO hemolytic disease (ABO HD) in the two populations and to determine the relationship of intestinal parasitic infection of the mother to ABO HD in the infant. The incidence of ABO HD among UPRH at risk pregnancies (type O mother with type A or B infant) was 28.3% or 1 in 3.5 as compared with 18.4% or 1 in 5.4 of NCBH at risk pregnancies (P less than .05). Indirect Coombs' tests in cord sera, representing the passive transfer from mother to fetus of antibodies directed toward antigens on the infants' erythrocytes, were positive in 58.8% of UPRH at risk infants as opposed to 40.4% of NCBH at risk infants (P less than .001). Maternal isohemagglutinin titers at term were higher in type O UPRH mothers than in type O NCBH mothers (P less than .01). A relationship between helminth parasitic infection of the mother and ABO HD in the infant was suspected but not proved.