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Cigarette smoking and pregnancy I: ovarian, uterine and placental effects.

This review examines the major observations and principal controversies relating to the effects of smoking and the constituents of tobacco on ovarian, uterine and placental tissues. Maternal exposure is assessed relative to specific tobacco-related chemicals and the feto-placental impact of mutagenic products, in addition to nicotine replacement as a pharmacological intervention for smoking cessation. Important new information is being learned from clinical in vitro fertilization and assisted reproduction technologies regarding the effects of smoking on fertility. Present evidence supports an adverse effect of smoking on ovarian function which is prolonged and dose-dependent, whereas there appear to be more reversible effects on implantation and ongoing pregnancy. The anti-oestrogenic effect of smoking is reviewed in terms of direct effects of nicotine, cadmium and polyaromatic hydrocarbons on oestrogen synthesis and metabolism, oocytes and granulosa-luteal function. Innovative new models provide evidence that smoking may alter fertility through effects on uterine-fallopian tube functions which mediate gamete and conceptus transport. It is of interest that smoking is associated with a decreased incidence of uterine fibroids, endometriosis and uterine cancer, which may reflect inhibitory effects of smoke constituents on uterine cell proliferation and extracellular matrix interactions. The increased miscarriage rate among mothers who smoke may be related to direct adverse effects of nicotine, cadmium and polyaromatic hydrocarbons on trophoblast invasion and proliferation. In this respect, alterations in trophoblast differentiation along invasive or proliferative pathways may explain the changes in endocrine function and vascular morphology that are observed in smokers. In summary, significant advances are being made in the understanding of cellular and molecular mechanisms which underlie the differential effects of cigarette smoking on reproductive tissues.

Embryo Implantation↗

Influence of thyroxine on human granulosa cell steroidogenesis in vitro.

PURPOSE: The objective of this study was to investigate the influence of thyroid hormone on estradiol and progesterone secretion of human granulosa cells maintained in vitro. METHODS: Granulosa cells were obtained by aspiration of preovulatory follicles of woman undergoing assisted reproductive technology. Ovulation induction was performed with GnRH agonist, hMG, and hCG. RESULTS: Granulosa cells were maintained in vitro in a defined medium with added insulin. Twenty-four-hour estradiol and progesterone secretion into the medium were determined for granulosa cells growing in serum-free medium and in serum-free medium with added T4 in a concentration range of 10(-7) to 10(-11) M. CONCLUSIONS: All concentrations of T4 used produced a statistically significant increase in progesterone secretion (range, 1.39 to 1.60 times the baseline amount). The increase in estradiol secretion reached statistical significance only at a T4 concentration of 10(-8) M (1.24 times the baseline amount).

Cells, Cultured↗

Cryopreservation, thawing, and transfer of human embryos.

Cryopreservation of human embryos is a routine procedure in most assisted reproductive technology laboratories. Embryos can be successfully frozen at the pronuclear, multicellular (four to eight blastomeres), and blastocyst stages. Each laboratory has to determine which freezing protocol is best suited for its patients. Freezing protocols have been developed that utilize cryoprotective agents such as glycerol, propanediol, dimethylsulfoxide, and sucrose. The purpose of these cryoprotectants is to help reduce the formation of intracellular ice when using a slow cooling protocol to freeze the embryos. The two most common ways to freeze embryos utilize either low concentrations of cryoprotectants and a slow stepwise freeze or high concentrations of cryoprotectants and a rapid freeze. Frozen-thawed embryos can be transferred to naturally cycling women or to women who have been primed with hormone replacement treatment with equal success.

Cryopreservation↗

Cryobiology ethics of human reproduction.

The article surveys the ethical and social issues that arise from recent developments in assisted reproductive technologies (ART) involving cryotechnology and argues that practitioners must understand ethical as well as technological issues. It discusses the risks associated with ART and the importance of the need to inform patients of them so that they can make considered decisions. It considers problematic areas in the use of ART, particularly the case of lesbian women who wish to conceive. It offers a philosophical definition of ethics and a framework for defining ethical, and unethical, clinical practice. It advocates a utilitarian approach to moral problems, one that attends to the moral consequences of actions. It examines the complex way that morality, law, and ethics interact and refers to controversial legal decisions in the United Kingdom concerning ART. This article considers the various rights (of donors, prospective parents, and offspring) that need to be taken into account by practitioners of ART.

Cryopreservation↗

Quality management systems in ART: are they really needed? An Australian clinic's experience.

As assisted reproductive technology (ART) expanded globally, several countries introduced prescribed requirements for treatment and monitoring of outcomes, as well as a licensing or accreditation requirement. While it is common for ART laboratories to be required to have an effective quality control system, the remainder of the clinic is often under less stringent regulation. Furthermore, when treatment conditions are prescribed, the standards tend to be conservative and clinics may choose to establish their own standards. Total quality management systems are now being used by an increasing number of ART clinics. In Australia and New Zealand, it is now a requirement to have a quality management system in order to be accredited and to help meet customer demand for improved delivery of ART services in these two countries.

Accreditation↗

The reproduction of America.

... This essay draws a connection between the medical procedures produced by new reproductive technologies, most specifically the use of pre-natal tests which result in abortion, and the dictates of American liberal theory. There is, I believe, a strong link between certain contemporary American abortion practices and American liberalism's formulation of and emphasis on rational individualism. The touchstone and criterion of reason as the sole measure of humanity has influenced the conditions under which we reproduce, and consequently, when we abort. Although America purports to offer certain kinds of freedom to all individuals, only those who exercise the capacity for rationality are in fact permitted to reap the benefits of liberal society.

Abortion, Eugenic↗

Assisted reproduction may change birth intentions.

OBJECTIVE: To determine whether the development and expansion of assisted reproductive technology (ART) between 1982 and 1995 raised the birth intentions of subfecund people relative to fecund people. DESIGN: Comparison of birth intention rates among fecund and subfecund women in the 1982, 1988, and 1995 rounds of the National Survey of Family Growth, standardized by age, parity, and education. SETTING: No clinical setting. PARTICIPANT(S): Nationally representative samples of married women who were 20 to 44 years old. INTERVENTION(S): None. RESULT(S): Between 1982 and 1995, birth intentions rose at least 2.5 times faster among subfecund women than among fecund women. This rise was not due to increasing average age at maternity over the period. CONCLUSION(S): The development of ART and expansion of services may well have increased birth intentions among subfecund women between 1982 and 1995.

Adult↗

Arab Americans, African Americans, and infertility: barriers to reproduction and medical care.

OBJECTIVE: To compare barriers to infertility care among African Americans and Arab Americans. DESIGN: Qualitative study using semi-structured reproductive histories and open-ended ethnographic interviews. SETTING: Infertile volunteers in a private IVF clinic in Dearborn, Michigan, an Arab American ethnic enclave community in metropolitan Detroit. PATIENT(S): Arab American men presenting for infertility diagnosis and treatment, including assisted reproductive technologies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Perceived barriers to effective infertility care. RESULT(S): Arab Americans and African Americans living in metropolitan Detroit are at increased risk of infertility and share similar histories of poverty, racism, and cultural barriers to medical treatment. This study, which focused on infertile Arab American men living in or near Dearborn (an ethnic enclave community composed mainly of recent immigrants and war refugees), revealed significant barriers to effective infertility care, including economic constraints, linguistic and cultural barriers, and social marginalization in mainstream U.S. society, particularly after September 11, 2001. CONCLUSION(S): Arab Americans experience disparities in access to infertility care, largely because of poverty and social marginalization in post-September 11th America.

Adult↗

Designing babies: what the future holds.

Advances in reproductive technology have opened new opportunities to avoid inherited diseases in offspring. The preimplantation genetic diagnosis (PGD) of human embryos permits those embryos carrying gene disorders or a non-diploid chromosome constitution to be identified. Numerous disease genes including those with a late onset have been identified and the conditions averted in children. Risks of abortion have been reduced, and the incidence of live births raised after PGD. It is also possible to select embryos with human leukocyte antigens (HLA) identical to those of a sick elder sibling, and then use stem cells from cord blood at birth to supply the necessary therapy. This form of treatment has alleviated the inherited disease in many recipients. The outlook and ethics of this approach to the alleviation of human disorders are discussed.

Ethics, Medical↗

Quantification of insulin-like growth factor I receptors on granulosa cells with flow cytometry after follicular stimulation.

The presence of insulin-like growth factor I (IGF-I) receptors on granulosa cells was investigated by flow cytometric analysis. Granulosa cells were retrieved from follicular fluid after oocyte retrieval during assisted reproduction technology procedures. Whole samples of follicular fluid were pooled and the cellular fraction analysed. In order to analyse granulosa cells only we developed a dual labelling technique whereby granulosa cells were identified as CD45 negative cells, distinguishing them from leukocytes which are CD45 positive. Analysis of the IGF-I receptor was done by staining the sample with a monoclonal anti-IGF-I receptor antibody (alphaIR3 clone) and goat anti-mouse phycoerythrin labelled antibody. After identification of the presence of IGF-I receptors, receptor expression was quantified by calibration of the fluorescence signals. We analysed 10 patients' samples and showed 559-1774 binding sites per granulosa cell with a mean value of 1125 +/- 382 (SD).

Female↗

The impact of treatment experiences on the course of infertility distress in male patients.

BACKGROUND: Previous research on infertile males has delivered equivocal findings on the course of infertility distress in males. The present longitudinal study examines whether there are differentials associated with specific treatment experiences (i.e. duration of treatment, the diagnosis received, and treatment failure of assisted reproductive technologies). METHODS: The sample consisted of 118 patients who twice visited an andrology clinic on their own initiative for fertility work-ups. Baseline and follow-up examinations were > or = 6 months apart. Prior to each fertility work-up, patients completed a questionnaire assessing distress due to infertility. RESULTS: No uniform course of distress could be detected. A significant interaction between treatment experiences indicated that distress rises significantly only in those patients who were in treatment > or = 17 months and experienced treatment failure between the first and the second psychological evaluation. For the diagnosis of male infertility, however, neither a direct nor an indirect impact was identified. CONCLUSION: The present study indicates that the interaction of specific treatment experiences is associated with changes in distress of infertile males.

Adult↗

Fertilisation and moral status: a scientific perspective.

The debate about the moral status of the embryo has gained new impetus because of the advances in reproductive technology that have made early human embryo experimentation a possibility, and because of the public concern that this arouses. Several philosophical arguments claiming that fertilisation is the event that accords moral status to the embryo were initially formulated in the context of the abortion debate. Were they formulated with sufficient precision to account for the scientific facts as we now understand them? Or do these arguments need modification? Aspects of three arguments for moral status being acquired at fertilisation are examined in relation to current scientific knowledge, highlighting the reasons why such arguments, at present, seem to provide an inadequate basis for the determination of moral status.

Beginning of Human Life↗

Addressing the growing problem of multiple gestations created by assisted reproductive therapies.

Iatrogenic multiple pregnancy is the most significant complication of assisted reproductive technology (ART). Approximately half of all children born subsequent to ART result from a plural gestation. Furthermore, the majority of triplets and higher order births are the product of ART. The risks for multiple pregnancy vary with practice patterns and the techniques used to achieve pregnancy. Recognizing the potential for serious morbidity associated with multiple pregnancies, infertility specialists have developed strategies to reduce the complication of multiple pregnancies while maintaining acceptable pregnancy rates. Implementation of these refined practices has led to a reduction in the incidence of higher order multiple births, although the incidence of twins has yet to be minimized. Further reduction in the incidence of multiple births after ART necessitates a redefinition of success to emphasize the healthy singleton birth rate, rather than crude pregnancy rates.

Female↗

Issues affecting commercialization of sexed sperm.

A decision tree for genetics or sperm-sexing entities considering sales of sexed sperm is discussed in terms of: (a) how best to avoid harm; (b) how best to do good; (c) needed synergy with other assisted reproductive technologies; (d) constraints on biotechnology; and (e) costs with current and likely technologies versus potential benefits to producers. The sexed-sperm industry might wish to take a pro-active stance on societal issues potentially affecting use of sexed sperm. For most sales in animal agriculture, cost of added value must be < 50% of benefit. Cost is less important for emotionally-driven uses with horses and human beings. Current procedures for flow-sorting allow most sperm to retain their fertilizing potential. Added cost to produce and package 2 x 10(6) sperm is estimated at US $30 to US $46 with flow sorted sperm. Estimating cost of any alternative technology is premature. For IVF/embryo transfer (ET), cost and numbers of flow-sorted sexed sperm are appropriate for commercial use. For use in low-dose AI, however, added cost to supply one insemination dose must be near US $12. Flow-sorting instruments with higher throughput and lower purchase and operating costs are obligatory for economic application in most AI situations. Developers of antibody-based separations also will face issues of retention of fertilizing potential while minimizing cell loss, separation of living from dead sperm concurrent with sperm sexing, output, and cost. To benefit producers and consumers in a changing world, genetics and sperm-sexing companies will have to collaborate and interface to provide funding for needed research and development and to recover these costs, using mechanisms not yet obvious.

Animals↗

Registration of congenital anomalies in ART populations: pitfalls.

Various methodological pitfalls preclude simple validation of the ostensible safety of offspring conceived thorough assisted reproductive technologies (ART). These pitfalls include lack of an appropriate comparison group (control), failure to take into account potential confounding variables, anomaly surveillance that is either too rigorous or too lax compared to the way in which anomalies are sought in general population surveys, and inconsistent criteria with respect to classifying anomalies (inclusion or exclusion of minor anomalies, internal anomalies evident only on ultrasound, and anomalies present in terminated pregnancies). To minimise these pitfalls, we recommend prospective surveillance for major anomalies, best defined as defects resulting in death, causing major handicap or necessitating surgery. Surveillance should ideally begin as soon as pregnancy is diagnosed. Data should be gathered allowing potential confounding variables to be taken into account, and systematic neonatal surveillance for anomalies should be performed during a designated time interval.

Confounding Factors, Epidemiologic↗

Ethical guidelines in genetics and genomics. An Islamic perspective.

We are at a time of unprecedented increase in knowledge of rapidly changing technology. Such biotechnology especially when it involves human subjects raises complex ethical, legal, social and religious issues. A World Health Organization expert consultation concluded that "genetics advances will only be acceptable if their application is carried out ethically, with due regard to autonomy, justice, education and the beliefs and resources of each nation and community." Public health authorities are increasingly concerned by the high rate of births with genetic disorders especially in developing countries where Muslims are a majority. Therefore, it is imperative to scrutinize the available methods of prevention and management of genetic disorders. A minimum level of cultural awareness is a necessary prerequisite for the delivery of care that is culturally sensitive, especially in Islamic countries. Islam presents a complete moral, ethical, and medical framework, it is a religion which encompasses the secular with the spiritual, the mundane with the celestial and hence forms the basis of the ethical, moral and even juridical attitudes and laws towards any problem or situation. Islamic teachings carry a great deal of instructions for health promotion and disease prevention including hereditary and genetic disorders, therefore, we will discuss how these teachings play an important role in the diagnostic, management and preventive measures including: genomic research; population genetic screening pre-marital screening, pre-implantation genetic diagnosis; assisted reproduction technology; stem cell therapy; genetic counseling and others.

Female↗

Ex vivo early embryo development and effects on gene expression and imprinting.

The environment to which the mammalian embryo is exposed during the preimplantation period of development has a profound effect on the physiology and viability of the conceptus. It has been demonstrated that conditions that alter gene expression, and in some instances the imprinting status of specific genes, have all previously been shown to adversely affect cell physiology. Thus, questions are raised regarding the aetiology of abnormal gene expression and altered imprinting patterns, and whether problems can be averted by using more physiological culture conditions. It is also of note that the sensitivity of the embryo to its surroundings decreases as development proceeds. Post compaction, environmental conditions have a lesser effect on gene function. This, therefore, has implications regarding the conditions used for IVF and the culture of the cleavage stage embryo. The developmental competence of the oocyte also impacts gene expression in the embryo, and therefore superovulation has been implicated in abnormal methylation and imprinting in the resultant embryo. Furthermore, the genetics and dietary status of the mother have a profound impact on embryo development and gene expression. The significance of specific animal models for human assisted reproductive technologies (ART) is questioned, given that most cattle data have been obtained from in vitro-matured oocytes and that genes imprinted in domestic and laboratory animals are not necessarily imprinted in the human. Patients treated with ART have fertility problems, which in turn may predispose their gametes or embryos to greater sensitivities to the process of ART. Whether this is from the drugs involved in the ovulation induction or from the IVF, intracytoplasmic sperm injection or culture procedures themselves remains to be determined. Alternatively, it may be that epigenetic alterations are associated with infertility and symptoms are subsequently revealed through ART. Whatever the aetiology, continued long-term monitoring of the children conceived through ART is warranted.

Animals↗

Assessment of two devices for in vitro preparation of human sperm.

The aim of the study was to assess and compare the efficiency of the ZSC-II versus the Sperm Select techniques in preparing human sperm from normozoospermic patients for use in intrauterine insemination and other assisted reproductive technologies. Twenty-five patients were included in the study. Semen was collected at intercourse and processed via 2 sperm preparation methods. Recovery of motile sperm and other sperm qualitative measurements were evaluated before and after ZSC-II and Sperm Select sperm preparation. Sperm qualitative measurements were not significantly different after the ZSC-II and Sperm Select procedures (p > .05). Differences (p < .05) were noted between the 2 procedures in the number of sperm recovered. A higher survival rate (longevity test, 72 h) was observed after ZSC-II sperm preparation and recovery. The ZSC-II procedure yielded higher total motile sperm than the Sperm Select. The superiority in longevity may suggest possible advantages in obtaining higher fertilization and pregnancy rates.

Fertilization in Vitro↗