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Preparation for practice in the new millennium: a discussion of the moral implications of multifetal pregnancy reduction.

This article approaches the problem of multifetal pregnancy reduction from a moral perspective. It is one of many complex moral issues arising from reproductive technology and is one with which midwives and nurses are faced more frequently with advancing technology. The work is intended to be used as an educational tool for those who prepare tomorrow's nurses and midwives. The subject is discussed from three perspectives, the pregnant woman and her partner (clients), a midwife, and from a philosophical ethical perspective. In an attempt to introduce a degree of reality, the perspective of the clients is presented as a dialogue. The midwife's moral position and her professional difficulties are also discussed. The dialogue and discussion are supplemented with notes in which the issues raised by the characters are critically analysed and discussed. This article is designed to encourage reflection and critical thinking in tomorrow's health care professionals, and in those who have the responsibility of educating them for a future where reproductive technology is posed to generate more major moral quandaries.

Attitude of Health Personnel↗

Multifetal pregnancy in older women and perinatal outcomes.

OBJECTIVE: To examine multifetal pregnancy in older women and perinatal outcomes. DESIGN: A cross-sectional study. SETTING: A nationwide vital registry. PATIENT(S): A national population-based database that links the live birth, fetal, and infant death certificates reported of multiple gestations in the United States from 1995 to 1997. It includes 155,777 twin and 5,630 triplet pregnancies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Very preterm birth (<33 weeks), very low birthweight (<1,500 g), and perinatal and infant deaths. RESULT(S): Compared with those with singleton pregnancies, women with multifetal gestation tended to be older, non-Hispanic white, better educated, married, and nulliparous and to have earlier and more frequent prenatal care. Pregnancies conceived by assisted reproductive technology accounted for an increasing number of multiple gestations in older women. In women with lower socioeconomic status, older age was associated with higher risks of poor perinatal outcomes in twin pregnancy (relative risks ranging from 1.0 to 1.9 with a dose-response pattern). However, in women with higher socioeconomic status, older women did not have a higher risk of poor perinatal outcomes than younger women. CONCLUSION(S): The effect of older maternal age on perinatal outcomes in multifetal pregnancies may have been altered by assisted reproductive technology, frequent prenatal surveillance, and advanced neonatal care.

Adult↗

The myth of the precious baby.

Each year tens of thousands of pregnancies are conceived through assisted reproductive technologies, and increasing numbers of pregnant women are aged older than 40 years. The obstetric management of these pregnancies, including more liberal recourse to cesarean delivery, has at times reflected the belief of providers that they are dealing with "precious babies". A leitmotif in discussions of the "precious child" is the concept that precious equates to irreplaceable (ie, mother who has tried harder to conceive may well have less chance to succeed again in the future). We believe that the obstetrician who decides to modify obstetric care because of these factors is, in fact, substituting physician assumption for patient autonomy. Although it is not counterintuitive to believe that a woman who has gone through assisted reproductive technologies would willingly (perhaps even eagerly) undergo cesarean delivery to avoid even remote risks, it is not safe to assume that women who conceived naturally would not. It is our contention that ultimately all women are best served if every pregnancy were treated as although it had preeminent value.

Cesarean Section↗

The importance of a genetic link in mothers commissioning a surrogate baby in the UK.

Reproductive technologies have enabled genetic and gestational links between parents and children to become separate from social relationships and inter-personal ties within families. The meaning of family is discussed, by drawing on research with infertile women who become parents as the result of surrogacy. The complexities of family are highlighted by addressing the consequences of babies carried and delivered by women who are not the biological parents of the child, or by women who are the biological mother of the child but who relinquish their genetic material to another woman. In all, 29 women completed a questionnaire on various aspects of their infertility, surrogacy, and the importance of a genetic link. The study identified some characteristics of women who have become mothers as a result of surrogacy, and some of their reactions to this way of creating families. In general, women who could use their own genetic material tended to believe a genetic link was important. Those who could not use their own genetic material were less uniform in their beliefs about the importance of a genetic link. The cognitive dissonance observed in this population has implications for the future of reproductive technology assisting couples in becoming a family with or without genetic relatedness.

Adoption↗

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.

Adult↗

Triplet heterotopic pregnancy after gonadotropin stimulation and intrauterine insemination diagnosed at laparoscopy: a case report.

Heterotopic pregnancy has been traditionally considered a rare event; however, with the use of assisted reproductive technology, the incidence of heterotopic pregnancies is increasing. Diagnosing a heterotopic pregnancy can be challenging. This report describes a 30-year-old female at 11 weeks' gestation with an intrauterine twin pregnancy after gonadotropin stimulation and intrauterine insemination who presented complaining of left lower quadrant abdominal pain with constipation and cramps. The patient was empirically treated for diverticulitis but failed to respond to therapy. A heterotopic triplet pregnancy was ultimately diagnosed at laparoscopy. Heterotopic pregnancy must be considered in the differential diagnosis of abdominal pain in the first trimester, especially in patients who conceived by means of assisted reproductive technology. Surgical treatment is the most frequently used method of treatment.

Abdominal Pain↗

Beneficial effect of microsurgical varicocelectomy is superior for men with bilateral versus unilateral repair.

PURPOSE: Varicocele represents the most common correctable cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Little is known about the differential effect of bilateral, compared to unilateral varicocelectomy, on male fertility potential. MATERIALS AND METHODS: A total of 369 consecutive varicocelectomies were performed for male factor infertility between July 1996 and July 2002. The outcomes measured include postoperative changes in semen parameters, pregnancy rates (assisted and unassisted) and use of assisted reproductive technology (intrauterine insemination and in vitro fertilization with intracytoplasmic sperm injection). RESULTS: There were 157 men who underwent bilateral and 212 who underwent unilateral left varicocelectomy. Both groups had comparable male and female ages, and baseline semen parameters. Semen parameters improved significantly after surgery in the bilateral and unilateral groups. Moreover, the improvement in percent motility was significantly greater in the bilateral compared to the unilateral group (8.0% +/- 1.7% compared to 4.4% +/- 1.5% improvement, respectively, p <0.01). In addition, the spontaneous pregnancy rate was significantly higher in the bilateral compared to the unilateral group (49% vs 36%, respectively, p <0.05). Assisted reproductive technology was comparable in the unilateral and bilateral groups (64% vs 51%, respectively, p >0.05). CONCLUSIONS: Our data indicate that bilateral varicocelectomy (for clinically palpable bilateral varicoceles) is associated with a significantly greater improvement in sperm quality (motility) and male fertility potential than unilateral varicocelectomy. The greater improvement in semen parameters and pregnancy outcome associated with bilateral varicocelectomy support the concept of a detrimental dose-effect of varicocele on male fertility potential.

Adult↗

Reasoning about embryos, cloning and stem cells: let's get more clear and distinct.

Plural democratic societies encourage and require the tolerance of disparate views. However, in relation to contentious areas like assisted reproductive technologies and destructive embryo research, tolerance is strained by the normative force of our fundamental beliefs about the moral status of early human forms. Yet in the continuing debates, spokespersons for different positions often do not concede all the implications of their arguments, may sidestep the real moral issues, and can fail to be clear about the foundations on which their arguments and policy advice ultimately rely. Guidelines and statutes can be rendered incoherent by the desire to balance and satisfy opposing values, rather than honestly reflecting the primary values they espouse. I call for greater clarity and honesty as these issues continue to be debated. An uncritical adherence to pluralism will encourage strategic obfuscation, but citizens of democracies need to be clearly informed about all the premises of opposing positions. Decisions about ethically and legally acceptable reproductive technologies ultimately depend on support for one metaphysical grounding at the expense of another. This should be acknowledged, as should its implications for policy.

Adult↗

Genetic and epigenetic risks of intracytoplasmic sperm injection method.

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.

Animals↗

Exploring the beliefs and experiences of potential egg share donors.

BACKGROUND: To date there are few attitudinal studies of women's experiences of egg donation, motivation to donate or their thoughts about eggs donated. Studies are predominantly discussed in terms of a specific treatment option and the ethical implications of different treatments. These studies are mainly designed by professionals working in assisted reproductive technology in line with a clinical agenda. AIM: This study aimed to explore the beliefs and experiences of potential egg share donors using an interpretative phenomenological methodology to equip health care practitioners to deal better with patients' needs and desires. METHOD: Open-ended interviews were conducted immediately following introductory consultations with 11 potential egg share donors from one fertility centre in the United Kingdom (UK). The sample was opportunistic. Data collection took 8 months and van Manen's interpretative phenomenological method was used. FINDINGS: Analysis revealed six themes of egg sharing: motherhood (the predominant theme within which all other themes could be subsumed), context, doubt, coping, exchange and empathy. Themes illustrated women's continuation with the scheme despite fears about giving away eggs, the parenting skills of recipient couples and future repercussions of positive outcomes for donor and recipient. CONCLUSIONS: Egg sharing could be seen as a marker of hope. Buoyed up by the possibility of a successful outcome, women are prepared to undertake repetitive treatment attempts despite continued failure to conceive and knowledge of a slim chance of a positive outcome. Implications for practice, policy and ethics result in recommendations for more in-depth interview work by independent researchers to gain a clearer picture of women's responses to reproductive technologies and the development of services in line with patient need and individual expectation.

Adaptation, Psychological↗

Recent decelerated decline in perinatal mortality rate of unlike-sexed twins in Japan.

The effect of assisted reproductive technology is more pronounced in unlike-sexed twins than in like-sexed. Trends in perinatal mortality of twins were compared between the two types of sex combination. Certificates for births (478,276 cases), stillbirths (50,542 cases), and early neonatal deaths (8747 cases) were the subjects of this analysis. Since 1984, the decline in the perinatal mortality of unlike-sexed twins has been slower than that of like-sexed twins. In both light-for-dates (LFD) and non-LFD, the decline in the gestational age standardised mortality ratio has been slower in unlike-sexed twins. We suggest this is due to the introduction of assisted reproductive technologies.

Birth Certificates↗

Complete down-regulation is not mandatory for good assisted reproductive treatment cycle outcomes.

OBJECTIVE: To determine the implications and predictive value of estradiol concentrations following pituitary down-regulation with gonadotrophin releasing hormone agonists in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology. STUDY DESIGN: A total of 277 patients undergoing ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) were enrolled into the study and the patients were divided into four groups according to estradiol levels on the initial day of stimulation of which group-A consisted of the patients who had < or =25 pg/ml (n=90), group-B with levels between 26 and 50 pg/ml (n=104), group-C with levels between 51 and 75 pg/ml (n=67) and group-D with levels > or =76-90 pg/ml (n=16) and the results were compared. The primary outcome measures included ovarian response and the clinical pregnancy rates. RESULTS: The clinical pregnancy rates in groups-A, B, C and D were 33.3% (30/90), 26.0% (27/104), 35.8% (24/67), and 25.0% (4/16), respectively, and there was no statistically significant difference (P=0.482). The mean number of oocytes retrieved in groups were (9.7+/-5.8, 10.3+/-6.5, 11.0+/-6.8, and 12.1+/-6.6), respectively (P=0.453) and the fertilization rates in groups-A, B, C and D were found to be similar (75, 80, 73 and 79%, respectively; P=0.658). CONCLUSION: Complete and deep desensitization obviously seems not to be mandatory for successful stimulation in assisted reproductive technology cycles.

Adult↗

Genetic ties: are they morally binding?

Does genetic relatedness define who is a mother or father and who incurs obligations towards or entitlements over children? While once the answer to this question may have been obvious, advances in reproductive technologies have complicated our understanding of what makes a parent. In a recent publication Bayne and Kolers argue for a pluralistic account of parenthood on the basis that genetic derivation, gestation, extended custody and sometimes intention to parent are sufficient (but not necessary) grounds for parenthood. Bayne and Kolers further suggest that definitions of parenthood are underpinned by the assumption that 'being causally implicated in the creation of a child is the key basis for being its parent'. This paper examines the claim that genetic relatedness is sufficient grounds for parenthood based on a causal connection between genetic parents and their offspring. I argue that parental obligations are about moral responsibility and not causal responsibility because we are not morally accountable for every consequence to which we causally contribute. My account includes the conditions generally held to apply to moral responsibility, i.e. freedom and foreseeability. I argue that parental responsibilities are generated whenever the birth of a child is a reasonably foreseeable consequence of voluntary actions. I consider the implications of this account for third parties involved in reproductive technologies. I argue that under some conditions the obligations generated by freely and foreseeably causing a child to exist can be justifiably transferred to others.

Child↗

Transgene insertion induced dominant male sterility and rescue of male fertility using round spermatid injection.

Transgene insertions in the mouse often cause mutations at chromosomal loci. Analysis of insertion mutations that cause male sterility may lead to the identification of novel molecular mechanisms implicated in male fertility. Here we show a line of transgenic mice with dominant inheritance of male sterility (DMS) that was found amid several lines that were normally fertile. Transgene-positive males from this line invariably were sterile, whereas transgenic females and transgene-negative male littermates were fertile. Histologic analysis and TUNEL staining for apoptotic cells in DMS testis showed spermatogenesis arrest at metaphase of meiosis I (M-I), accompanied by massive apoptosis of spermatocytes. Meiosis I arrest was incomplete, however, as small numbers of spermatids and spermatozoa were found. Both round spermatids and spermatozoa were evaluated for their permissiveness in the assisted reproductive technologies intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI). Surprisingly, ROSI but not ICSI gave live offspring, suggesting that mature sperm had deteriorated by the time of recovery from the epididymis. Mapping the transgene insertion by fluorescence in situ hybridization revealed a site on chromosome 14 D3-E1. Two candidate genes, GFR alpha 2 and GnRH, that were previously mapped to that region and the functions of which in spermatogenesis are well established were not altered in DMS. As a consequence, positional cloning of the DMS locus will be essential to identify new molecules potentially involved in arrest at M-I. Furthermore, mice carrying this genetic trait might be useful for studies of assisted reproductive technologies and male contraceptives.

Animals↗

Mitochondrial dysfunction in mouse oocytes results in preimplantation embryo arrest in vitro.

Oocyte mitochondrial dysfunction has been proposed as a cause of high levels of developmental retardation and arrest that occur in human preimplantation embryos generated using assisted reproductive technology in the treatment of some causes of female infertility. To investigate this, a model of mitochondrial dysfunction was developed in mouse oocytes using a method of photosensitization of the mitochondrion-specific dye, rhodamine-123. After in vitro fertilization, dye-loaded and photosensitized oocytes showed developmental arrest in proportion to irradiation time. Morphological and metabolic assessments of zygotes indicated an increase in mitochondrial permeability that subsequently resulted in apoptotic degeneration. Development was partially restored by inhibition of mitochondrial permeability transition pore formation by oocyte pretreatment with cyclosporin A. Oocyte mitochondria are therefore physiological regulators of early embryo development and potential sites of pathological insult that may perturb oocyte and subsequent preimplantation embryo viability. These findings have important implications for the treatment of clinically infertile women using assisted reproductive technologies.

Animals↗

Long-term rock dove (Columba livia) primordial germ cell culture: A tool towards avian conservation.

Primordial germ cells (PGCs) are critical tools for genome engineering and conservation in birds. Although culture systems for chicken PGCs have been well established for nearly two decades, efforts to propagate PGCs from other avian species have proved exceptionally challenging, limiting the broader application of artificial reproductive technologies in birds. Here we report the first successful derivation and long-term culture of PGCs from the rock dove, or common pigeon (Columba livia). Guided by transcriptomic profiling of PGCs, we developed a species-specific medium that supports PGC maintenance and expansion. We identify insulin signaling as a requirement for survival under the conditions tested, and demonstrate that inhibition of the retinoic acid receptor, in the presence of vitamin A, supports propagation. Supplementation with bone morphogenetic protein 4, leukemia inhibitory factor (LIF), glial cell line-derived neurotrophic factor, and pleiotrophin further enhances PGC proliferation. Cultured cells express canonical germline markers and migrate to the gonads following injection into both rock dove and chicken embryos, confirming functional migratory competency. These findings establish a platform for germline manipulation and biobanking in Columbidae, broadening the potential applicability of reproductive technologies to conservation efforts.

Animals↗

Reproductive biotechnologies: current status in porcine reproduction.

During the past decade, considerable attention has been directed toward the development of reproductive technologies for both research purposes and for more controlled swine reproduction. Artificial insemination is an example of a technology that has continued to be expanded from early use in European countries to the USA and Canada where it is now estimated that a majority of the sows bred are artificially inseminated. In addition, several significant technological advancements have been made in the genetic modification of swine and interest has been generated in the possible use of swine as donors of specific tissues and of organs for the improvement of human health. At the same time, the systems for production of swine for human food continue to undergo major changes including, in some countries, the consolidation of swine into large, integrated units. These swine operations are very receptive to the use of technologies to reduce labor costs as well as a basis for increased production efficiency. Therefore, the combined interest in swine reproductive technologies by both the medical field and the swine industry creates an increased effort for the development of new technologies as well as for the implementation of existing ones. One of the more rapid technological advancements this decade has been the progress in in vitro production (IVP) of swine embryos. Major advancements have been made on the development of procedures for production of large numbers of embryos from oocytes collected at slaughter houses which are then matured (IVM) and fertilized (IVF) in the laboratory. Success in IVP has stimulated increased research in other areas that can be enhanced by the availability of embryos without a requirement for surgical collection from gilts or sows. One example is the combined use of IVF, gender-sorted sperm cells, and embryo transfer to produce offspring of a predicted sex. In a related area, instrumentation for non-surgical embryo transfer has recently been developed that results in significant improvement in this technology. Similar achievements have been gained in cryopreservation of embryos by vitrification. These developments will be reviewed with emphasis on the in vitro production of embryos from immature oocytes.

Animal Husbandry↗

Pregnancy rates after embryo transfer depend on the provider at embryo transfer.

OBJECTIVE: To evaluate the effect of individual providers on pregnancy outcome after embryo transfer. DESIGN: Retrospective data analysis. SETTING: University-based tertiary-care assisted reproductive technology program with 10 physician-providers. PATIENT(S): Six hundred and seventeen women who underwent 854 fresh embryo transfers between January 1996 and January 1999. INTERVENTION(S): Pregnancies after embryo transfer were recorded for each provider. MAIN OUTCOME MEASURE(S): Establishment of a clinical pregnancy. RESULT(S): Three hundred ninety-three clinical pregnancies resulted from 854 embryo transfers, for an overall clinical pregnancy rate of 46.0% per embryo transfer. Three hundred forty-seven (40.6%) pregnancies were ongoing. The clinical pregnancy rate varied significantly between providers: for example, 17.0% (47 transfers) vs. 54.3% (57 transfers) (P<.05). Similarly, the ratio of high-grade embryos required to produce a gestational sac differed between providers. The number or quality of embryos transferred did not differ significantly. CONCLUSION(S): Significant differences were observed in pregnancy rates after embryo transfer done by different providers, suggesting that embryo transfer technique may influence pregnancy outcome in assisted reproductive technology.

Adult↗