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Candidate selection and psychosocial considerations of in-vitro fertilization procedures.

The psychological impact of the new reproductive technology should not be understated. The history of infertility treatment and failure to achieve pregnancy that most couples bring to the program, along with their hopes and expectations for success, makes them extremely vulnerable to anxiety, unrealistic expectations, and grief reactions. When a cycle of IVF fails, the intensity of the experience and the disappointment may be overwhelming for a while, but most couples are willing to try it again. One patient wrote about her feelings after IVF treatment after having read comments in a popular magazine which implied that medical science was taking control of reproduction. Those of us who go through in-vitro fertilization think long and hard about what we are doing. Most of us weigh the pros and cons very thoroughly. We weigh the risks to our potential children just as people who have genetically linked diseases do before they conceive. (Our fetuses are not "bombarded" by ultrasound procedures any more than many other pregnant women's fetuses are these days.) Most of us are thankful that the technology is now available to us, if we choose to participate. Physicians who work with IVF patients do realize that the procedure is stressful. Often the stress is viewed as primarily the patients', and we are asked to study the level of stress. To a large extent that is the subject matter of this chapter. Nevertheless, the stress is perceived because the physicians and staff are also under stress. The failure of an IVF cycle is immediately known to the health care givers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Infertility in the third millennium: implications for the individual, family and society: condensed meeting report from the Bertarelli Foundation's second global conference.

Primary infertility is a key issue in the developed world, while the developing world has high rates of secondary infertility. The impact of HIV/AIDS on fertility is insufficiently explored. One of the most important barriers to access to infertility treatment is cost; at the same time the role of social and cultural factors in restricting access should not be underestimated. IVF has become the standard therapy for female infertility, and ICSI for infertility of the male partner. However, the use of these therapies should not be initiated without a thorough investigation and, whenever possible, individual diagnosis of the underlying causes of infertility. Multiple gestation remains one of the most challenging and controversial issues in the treatment of infertility. Current IVF practices are often blamed for this; in this respect, attention should also be focused on the role of ovarian stimulation in ovulation induction. National guidelines and national registries for assisted reproductive technology (ART) are becoming more widespread and are expected to play an important role in promoting best practice in ART in the future.

Adult↗

Modalities for treatment of antisperm antibody mediated infertility: novel perspectives.

Immunoinfertility because of antisperm antibodies (ASA) is an important cause of infertility in humans. The incidence of ASA in infertile couples is 9-36% depending on the reporting center. Early claims regarding the incidence and involvement of ASA in involuntary infertility were probably overemphasized, which has resulted in subsequent confusion, doubt, and underestimation of their clinical significance. No immunoglobulin that binds to sperm should be called an antisperm antibody in a strict sense unless it is directed against a sperm antigen that plays a role in fertilization and fertility. ASA directed against the fertilization-related antigens are more relevant to infertility than the immunoglobulins that bind to sperm associated antigens. Several methods have been reported for treatment of immunoinfertility. These include: immunosuppressive therapies using corticosteroids or cyclosporine; assisted reproductive technologies such as intrauterine insemination, gamete intrafallopian transfer, in vitro fertilization, and intracytoplasmic sperm injection; laboratory techniques such as sperm washing, immunomagnetic sperm separation, proteolytic enzyme treatment, and use of immunobeads. Most of the available techniques have side effects, are invasive and expensive, have low efficacy, or provide conflicting results. Recent findings using defined sperm antigens that have a role in fertilization/fertility have provided animal models and innovative novel perspectives for studying the mechanism of immunoinfertility and possible modalities for treatment. The better understanding of local immunity and latest advances in hybridoma and recombinant technologies, proteomics and genomics leading to characterization of sperm antigens relevant to fertility will help to clarify the controversy and to establish the significance of ASA in infertility.

Adrenal Cortex Hormones↗

Regulatory approaches to reproductive genetic testing.

This report analyses the ethical and legal aspects of reproductive genetic testing in 11 countries (Australia, Austria, Canada, France, Germany, India, Israel, Japan, The Netherlands, Switzerland and the UK). The legal status of reproductive genetic testing in the countries under analysis is difficult to generalize due to the different regulatory systems adopted. These approaches are a reflection of the legal traditions and cultural and socio-religious beliefs which inform and shape public policy on assisted reproductive technologies and genetic testing. We divide approaches into two groups: public ordering (legislative, top-down approach) and private ordering (non-legislative, bottom-up approach). Even limiting our analysis to a number of countries that span the range from restrictive to pragmatic approaches, there is remarkable symmetry in both the (i) substantive requirements (i.e. gravity, health indications generally) and (ii) procedural safeguards (i.e. informed consent, counselling, confidentiality, civil status, oversight and accreditation) surrounding reproductive genetic testing. Indeed, irrespective of whether a country adopts a prohibitive or a permissive approach through legislation or self-regulation or a mix of both, the ultimate decision is--and should continue to be--a medical one. Nowhere is this more evident than in the substantive requirements.

Confidentiality↗

Molecular biology of fertilization.

Our understanding of molecular mechanisms of fertilization in mammals has lagged behind the rapid development of reproductive technology over the last decade. Significant advances in knowledge have resulted mainly from studies in laboratory animals in vitro. However, this situation has changed in the last few years as targeted mutagenesis in mice has provided important new information about genes and proteins involved in basic aspects of sperm-egg interactions in vivo. In this brief review the current knowledge about the generic aspects of mammalian fertilization is summarized, together with particular features of reproductive physiology related to cats and dogs.

Acrosome Reaction↗

Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method.

Vitrification is frequently referred to as a novel technology of cryopreservation in embryology, although some young embryologists were born after its first successful application. Unfortunately, in spite of the accumulated evidence regarding its enormous potential value, most domestic animal and human laboratories use exclusively the traditional slow-rate freezing with its compromised efficiency and inconsistency. The purpose of this paper is to clarify terms and conditions, to summarize arguments supporting or disapproving the use of vitrification, and to outline its role among assisted reproductive technologies. To provide evidence for the potential significance of vitrification, achievements with the Cryotop technology, an advanced version of the "minimal volume approaches" is analyzed. This technology alone has resulted in more healthy babies after cryopreservation of blastocysts than any other vitrification technique, and more successful human oocyte vitrification resulting in normal births than any other cryopreservation method. The value of this method is also demonstrated by achievements in the field of domestic animal embryology. A modification of the technique using a hermetically sealed container for storage may help to eliminate potential dangers of disease transmission and open the way for widespread application for cryopreservation at all phases of oocyte and preimplantation embryo development in mammals.

Animals↗

Identified and unidentified challenges for reproductive biotechnologies regarding infectious diseases in animal and public health.

The aim of the present paper is to review the known and theoretical risks for in vivo derived and in vitro produced embryos as well as for nuclear transferred or transgenic embryos in terms of animal diseases or diseases of public health consequence. For in vivo derived embryos, a considerable number of experiments and scientific investigations have resulted in recommended guidelines and procedures that ensure a high level of safety. The effectiveness of these measures has been validated by field experience with the safe transfer of several million embryos over the past three decades. In vitro produced embryos have several characteristics that differentiate them from the former, in particular a structure of the zona pellucida that results in a more frequent possible association of pathogens with the embryo. However, the guidelines prescribed by the IETS, the international standard setting body (OIE) and existing national regulatory frameworks are in place to minimize the risk of disease transmission. No specific public health risks have been identified to date with respect to in vivo or in vitro derived embryos. In regard to nuclear transferred and transgenic embryos, theoretical risks have been identified in relation to the potential effects on some intrinsic viruses such as endogenous retroviruses but very little targeted experimental work has been carried out on infectious diseases that could have adverse consequences on animal or human health. Although there has been no report of such adverse consequences associated with the limited number of animals produced to date by such reproductive technologies, a precautionary approach is warranted given the potential negative impacts and it would be prudent to restrict at this stage, the international movement of such "manipulated" embryos.

Animals↗

[Male sterility].

Recently several studies have suggested a decline in the quality of semen. About half of the infertile causes are in men, the rate is increasing in the infertile couples. There are some therapy for the male sterility; medication, surgery or assisted reproductive technology (ART). Medicinal effects are not expected, and surgical cases are localized for indication. Moreover, since most of male sterility are idiopathic insufficiency of spermatogenesis, a recent tendency in the male sterile therapy is ART such as IVF-ET, ICSI, TESE, etc.

Humans↗

Nocturnal sperm emission in men with psychogenic anejaculation.

OBJECTIVE: To evaluate sperm characteristics and fertilization potential in sperm obtained from nocturnal emission in men with psychogenic anejaculation. DESIGN: Retrospective study. SETTING: In Vitro Fertilization Unit, Bikur Cholim Hospital, Jerusalem, Israel. PATIENT(S): Six men with psychogenic anejaculation. INTERVENTION(S): Nocturnal emission, electroejaculation, sperm cryopreservation, and assisted reproduction technologies. MAIN OUTCOME MEASURE(S): Semen analysis, intracytoplasmic sperm injection (ICSI), fertilization rates. RESULT(S): In four patients, the concentration and motility of sperm obtained from freeze-thawed nocturnal emission were decreased compared with sperm from electroejaculation. Fertilization rates after ICSI using the nocturnal emission sperm were relatively low (45%). One clinical pregnancy was achieved after intrauterine insemination. CONCLUSION(S): The quality of sperm from nocturnal emissions is variable, but it can be used in assisted reproduction procedures to avoid aggressive procedures such as electroejaculation or testis biopsy.

Adult↗

Safety, identity and consent: a limited defense of reproductive human cloning.

Some opponents of reproductive human cloning have argued that, because of its experimental nature, any attempt to create a child by way of cloning would risk serious birth defects or genetic abnormalities and would therefore be immoral. Some versions of this argument appeal to the consent of the person to be conceived in this way. In particular, they assume that if an experimental reproductive technology has not yet been shown to be safe, then, before we use it, we are morally obligated to get either the actual consent or the presumed consent of the person to be conceived. In this article, I attempt to explain the appeal of such consent-based arguments as deriving from a mistaken view of personal identity. I then argue that since this view is false, such arguments are unsound. Finally, I argue that even if reproductive cloning is unsafe, it may still be morally permissible in some circumstances.

Cloning, Organism↗

Gamete cryopreservation in the domestic cat.

Cryopreservation of gametes is an important tool for the improvement of assisted reproductive technologies. In-depth studies of spermatozoon and oocyte characteristics are required in order to define efficient protocols for the maintenance of viability, including fertilizing and developmental ability, of gametes after thawing. In the domestic cat, semen cryopreservation techniques still produce variable results, the cryopreservation of oocytes is at an experimental level and there have been only a few attempts at cryopreserving gonadal tissue. However, each procedure has generated promising results and has important implications, both for improving reproductive performance of valuable breeds of domestic cats and for conservation of biodiversity in endangered felids by reclamation of valuable male and female germplasm.

Animals↗

ESHRE Task Force on Ethics and Law 10: surrogacy.

This 10th statement of the Task Force on Ethics and Law considers ethical questions specific to varied surrogacy arrangements. Surrogacy is especially complex as the interests of the intended parents, the surrogate, and the future child may differ. It is concluded that surrogacy is an acceptable method of assisted reproductive technology of the last resort for specific medical indications, for which only reimbursement of reasonable expenses is allowed.

Advisory Committees↗

Expression of vascular endothelial growth factor in human luteinizing granulosa cells and its correlation with the response to controlled ovarian hyperstimulation.

Ovulation induction represents one of the most important steps for the success of assisted reproductive technology (ART) procedures. To better understand the mechanisms that regulate follicle growth, oocyte maturation, and ovarian steroidogenesis, we investigated the correlations between vascular endothelial growth factor (VEGF) gene expression in human luteinizing granulosa cells, steroid production and oocyte retrieval in patients undergoing controlled ovarian hyperstimulation. We evaluated the messenger ribonucleic acid (mRNA) for VEGF in human luteinizing granulosa cells obtained at the time of oocyte retrieval from 24 women participating in an in vitro fertilization program at the Reproductive Endocrinology Center of our Department of Obstetrics and Gynecology. We found a positive linear correlation of VEGF mRNA with estradiol and progesterone serum levels at the day of oocyte retrieval (p < 0.05). Furthermore, VEGF mRNA expression was significantly higher in granulosa cells obtained from patients with an elevated number of oocytes and high fertilization rate (p < 0.05). Our data confirm that VEGF may play an important role in the regulation of vascular development during follicular growth and luteal differentiation.

Corpus Luteum↗

Compensating egg donors. Is the money worth it?

When infertility clinics throughout the state doubled egg donor compensation to $5,000 last year, assisted reproductive technologies gained a heightened level of public awareness. Although the bold move prompted ethical debate about egg donation, offers of generous remuneration are helping many New Jersey infertility clinics maintain a steady pool of qualified donors.

Cost Control↗

Female poor responders.

Female poor responders are represented by normovulatory women showing a 'gonadal failure' in term of inadequate number of recruited follicles under conventional controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART). ARTs offers today a high chance of pregnancy to infertile couples when a normal ovarian response provides a large choice of embryos for transfer. On the contrary, failure of the ovary to produce enough oocyte for treatment, reduces significantly the likelihood of conceiving in ART, not only in the treatment cycle, but also predicting a poor prognosis in subsequent cycles. Up to date, poor response remains one of the most frequent problems in the field of assisted reproduction. First described in 1981, poor response has been investigated by several authors, but many aspects are still controversial. In this paper definition, pathophysiology and management of poor response are revised and discussed.

Estradiol↗

The treatment of obstructive azoospermia in male infertility--past, present, and future.

Until recently, the primary treatment option for infertile men with obstructive azoospermia was the reconstruction of the male seminal tract when the causes of obstruction were reconstructable. For unreconstructable causes, such as congenital absence of the vas deferens, the primary treatment option involved implantation of an alloplastic artificial spermatocele for subsequent percutaneous retrieval of sperm. Retrieved sperm was then used for intrauterine insemination. The introduction of in vitro fertilization (IVF), performed together with microsurgical epididymal sperm aspiration (MESA), provided new frontiers for the treatment of unreconstructable obstructive azoospermic infertility in men. Against this background, the author reviewed the past and present status of the treatment of obstructive male infertility for the purpose of seeking a future course for the treatment of obstructive azoospermia. At the Andrology Clinic, 246 (26%) of 963 infertile males revealed azoospermia and 72 (29%) of these 246 patients showed obstruction at the seminal tract, showing that 7.5% of male infertility cases were caused by ductal obstruction. Microsurgical reconstruction of the seminal tract was performed, including vasovasostomy (29 cases), epididymovasostomy (18 cases), and artificial spermatocele implantation (20 cases). Vasovasostomy resulted in an 81.3% patency rate and a 37.5% fertility rate. Epididymovasostomy showed a 71% patency rate and a 29% fertility rate. In contrast, artificial spermatocele implantation resulted in positive sperm present in the aspirated fluid in 33.3% of the patients; however, no pregnancy was achieved by artificial insemination using aspirated sperm. MESA together with assisted reproductive technology (ART) in 14 patients showed 79% ovum fertilization rates and a 35.7% clinical pregnancy rate. Thus, this new technique could open new frontiers for the future treatment of obstruction of the male seminal tract which cannot be reconstructed by vasovasostomy or vasoepididymostomy.

Epididymis↗

Current concepts of Down syndrome screening tests in assisted reproduction twin pregnancies: another double trouble.

Assisted reproductive technologies (ART) have increased both the number of pregnancies in women beyond the age of 35 and the incidence of multiple pregnancies. Various methods of screening for Down syndrome (DS) were introduced in clinical practice during the last two decades, and specific problems were encountered when they were applied for twin pregnancies. The current review aims to explore the problematic issue of prenatal DS screening in ART twins. Overall, more women with twin pregnancies (mainly those who conceived via assisted reproduction) are found to be false positive for DS. This is because mid-trimester maternal serum screening is associated with a higher false-positive rate secondary to changes in the feto-placental endocrinologic metabolism, reflected mainly in high human chorionic gonadotrophin (hCG) levels in the ART pregnancies. First-trimester nuchal translucency (NT) measurement in twin pregnancies is not affected by the problems encountered in serum screening. This sonographic screening approach enables a fetus-specific identification of those fetuses at high risk of DS and is associated with a lower false-positive rate than mid-trimester serum screening. DS screening in ART twins presents several challenges in determining the most appropriate screening test modality. Whether there is any significant benefit of adding first-trimester biochemistry or nasal bone scanning in screening ART-conceived twins awaits further investigation.

Chorionic Gonadotropin, beta Subunit, Human↗

Multiple births and outcome.

The rate of multiple-gestation pregnancies has grown exponentially over the last few decades and is responsible for the steady increase in the birth rate of low-birth weight infants. As a group, infants of multiple-gestation pregnancies have higher mortality and morbidity than singleton pregnancies. The increase in adverse outcomes is related directly to the increased risk for preterm delivery and low-birth weight, and not to the multiple gestation itself. Outcomes for multiple-gestation infants appear to be similar whether conceived spontaneously or through artificial reproductive technology. Efforts to reduce the birth rate of low-birth weight infants should target multiple-gestation pregnancies.

Birth Rate↗