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Outcome of ICSI in HIV-1-infected women.

BACKGROUND: Since 2001, French law has permitted the use of assisted reproductive technology in human immunodeficiency virus (HIV)-1 infected women under strict conditions. This report describes a preliminary series of seropositive women who underwent assisted reproduction treatment at our facility. To minimize contamination of culture media, equipment, and therefore of male gametes and embryos, we chose to perform ICSI in all cases. The outcome of ICSI was compared with the outcome in an age-matched group of non-HIV-1-infected women. Since several previous reports have indicated that HIV infection may be associated with a decrease in spontaneous fertility, our goal was also to assess the fertility status of the HIV-1-infected women entering our ICSI programme. METHODS: The French law governing the use of assisted reproduction protocols in HIV-1-infected women was strictly applied. The inclusion criteria were absence of ongoing disease, CD4((+)) count >200 cells/mm(3), and stable HIV-1 RNA level. Since mean age at the time of ICSI was higher in HIV-1-infected women than in the overall group of non-HIV-infected women, we compared outcome data in HIV-1-infected women (group I) to a group of non-HIV-1-infected women matched with regard to age and follicle retrieval period (group II) as well as to the overall group of women who underwent ICSI at our institution (group III). RESULTS: A total of 66 ovarian stimulations was performed in 29 HIV-1-infected-infected women. The percentage of cancelled cycles was higher in infected women than in matched controls (15.2 versus 4.9%, P < 0.05). The duration of ovarian stimulation (13.3 versus 11.7 days, P < 0.05) and amount of recombinant FSH injected (2898 versus 2429 IU, P < 0.001) were also higher in infected women. The number of retrieved oocytes, mature oocytes, and embryos obtained as well as embryo quality was similar in all groups. The fertilization rate was higher in infected women than in matched controls (67 versus 60%, P < 0.01). The pregnancy rate was not significantly different between groups I and II (16.1 versus 19.6%) in spite of the fact that the number of embryos transferred was purposefully restricted in the HIV-1-infected group to minimize multiple pregnancy (2.0 versus 2.4, not significant). CONCLUSION: The results of this preliminary series of ICSI cycles in HIV-1-infected women indicate that optimal ovarian stimulation is slightly more difficult to achieve than in matched seronegative women. However, when criteria for oocyte retrieval were fulfilled, ICSI results were similar to those of age-matched controls.

Adult↗

Nuchal translucency in dichorionic twins conceived after assisted reproduction.

OBJECTIVES: As opposed to biochemical markers of Down syndrome, nuchal translucency (NT) was once thought to be a more reliable screening marker for high order multiple pregnancies and pregnancies conceived after assisted conception. Recent data suggested that NT in singleton fetuses from assisted reproduction technology (ART) was thicker than those from singleton pregnancies. The present study compared the thickness of NT in dichorionic twins from natural conception and assisted reproduction. METHODS: A retrospective analysis for comparison of NT thickness on 3319 spontaneous singletons, 19 pairs of spontaneous twins and 27 pairs of assisted reproduction twins was performed. RESULTS: The median NT multiple of median (MoM) of spontaneous singletons was 1.00. For twins, the median NT MoM for pregnancies after assisted reproduction and natural conception were 1.02 and 1.07 respectively. There was no statistical difference in the NT thickness among the three pregnancy groups. CONCLUSION: Contrary to the observed increase in NT in singleton pregnancies from assisted reproduction, the NT in dichorionic twins was comparable to the spontaneous ones. The mode of conception appears to impose differential influence on singletons and twins.

Female↗

Endometriosis-associated infertility.

Despite intense clinical interest and increasingly sophisticated diagnostic techniques, we know surprisingly little of the relationship between endometriosis and infertility or the mechanism of infertility in these couples. No therapy specifically directed toward the ectopic endometrial implants, medical or surgical, has been demonstrated to improve the likelihood of pregnancy for couples with endometriosis-associated infertility. This is consistent with the observation that, in the absence of mechanical distortion of the pelvic viscera, no therapy directed against the implants improves the likelihood of pregnancy in these couples. The reason for this lack of progress is most probably that the mechanism of infertility in these couples remains to be determined. At present, it would be more accurate to say that these couples have unexplained infertility. The most promising therapeutic approach is to treat women with endometriosis-associated infertility with a non-specific cycle fecundity enhancing technique. Typically this is one of the newer assisted reproductive technologies such as controlled ovarian hyperstimulation with intrauterine insemination of capacitated sperm. Since the fecundity of many of the women with endometriosis in the later reproductive years is rapidly declining, this may represent their most cost-effective option for establishing a pregnancy. Only with further effort directed towards determining the mechanisms of infertility in these couples will a more effective therapy be forthcoming.

Causality↗

The social epidemiology of coping with infertility.

BACKGROUND: To analyse the cross-sectional association between coping responses with infertility and occupational social class. Infertility is evenly distributed across social classes in Denmark, and there is free access to high-quality assisted reproduction technology. METHODS: Data were based on a questionnaire in a consecutive sample of 1169 women and 1081 Danish men who were about to begin assisted reproduction treatment. The coping measure was developed from an adaptation of Lazarus and Folkman's Ways of Coping Questionnaire and based on results from interviews with infertile people. The measure was developed in four categories: active-avoidance coping; active-confronting coping; passive-avoidance coping; meaning-based coping. These subscales were later confirmed by factor analysis. Occupational social class was measured in a standardized way. RESULTS: Contrary to expectations, the logistic regression analyses showed that women from lower social classes V + VI and men from social classes III + IV used significantly more active-confronting coping. Women from lower social classes V + VI used significantly more meaning-based coping. Both men and women from social classes III - VI used significantly more passive-avoidance coping and significantly less active-avoidance coping. CONCLUSION: Due to the significant social differences in coping with infertility, the study suggested that elements of coping may be learned from one's social network and reference group.

Adaptation, Psychological↗

Blastocyst versus early cleavage embryo transfer: a retrospective analysis of 4,165 transfers.

PURPOSE: To compare the clinical outcomes after the transfer of blastocysts versus early cleavage embryos in assisted reproduction technologies (ART). METHODS: A retrospective analysis of all the ovarian stimulation-in vitro fertilization-embryo transfer cycles performed at the Centre for Human Reproduction, Athens, Greece, between June 1997 and December 2001. RESULTS: The number of blastocysts transferred per ET was significantly lower compared to that of all early cleavage embryos. The implantation rate of blastocysts was significantly higher compared to that of all other modes of transfer. Clinical pregnancy rate after the transfer of blastocysts was significantly increased compared to that after transfer of any early cleavage embryo. The viable pregnancy rate after the transfer of blastocysts was significantly increased only compared to that after the transfer of day-2 embryos. There were no significant differences regarding the multiple gestation rates among the various modes of transfer. CONCLUSION: The use of blastocysts in ART is beneficial when compared to that of day-2 embryos and at least comparable to that of day-3 embryos. Blastocyst culture and transfer remains a favourable and promising option in ART.

Adult↗

In-vitro developmental potential of individual mouse blastomeres cultured with and without zona pellucida: future implications for human assisted reproduction.

This study was designed to compare the developmental potential of individual blastomeres derived from 2-, 4-, 6- and 8-cell mouse embryos cultured with and without zona pellucida (ZP). In the first series, one, three, five and seven blastomeres were biopsied from 2-, 4-, 6- and 8-cell embryos respectively, and inserted individually into empty ZP recipients, leaving the remaining blastomere within its original ZP. In the second series, the same protocol was used except that the biopsied blastomeres were cultured without ZP and compared with the remaining blastomere within its original ZP. For the first series, individual blastomeres derived from 2-, 4-, 6- and 8-cell embryos cultured with ZP showed blastocyst development of 82.4, 68.6, 44.4 and 23.1% respectively, with corresponding hatching rates of 70.6, 60.0, 25.9 and 7.7%. For the second series, individual blastomeres cultured without ZP progressed with blastocyst development of 73.3, 64.5, 35.7 and 22.7% respectively. Blastocyst multiplication was achieved most efficiently when using individual blastomeres from 4- and 6-cell embryos. This is the first report on comparative in-vitro propagation of single blastomeres derived from various cleavage stages in a mammalian species. Blastomere cloning with its multiple applications may be envisaged for human assisted reproductive technologies.

Animals↗

Interventions in reproduction.

Assisted reproductive technology has helped many childless couples. It has also raised questions about how appropriate the technology might be in different situations. How we understand parenthood is crucial in taking a stand on such scientific intervention. It is suggested that physicians should decide on offering artificial insemination, surrogacy and in-vitro fertilisation only after considering if the child will have good parents and if there will be legal complications from the use of the technology.

Female↗

Manipulation of canine fertility using in vitro culture techniques.

Highlighting the important aspects of canine reproductive physiology, this review documents developments made with in vitro culture of canine gametes, and indicates how these techniques can be further exploited. In vitro culture of gametes and embryos has been achieved in many mammalian species, allowing the development of reproductive technology. Despite numerous investigations in other species, only a small number have been performed in dogs. Further studies are required to establish the differences between canine reproductive physiology and that of other mammals. Ultimately, these studies may lead to the development of a gamete salvage technique incorporating oocyte, spermatozoa and embryo culture, and cryopreservation to allow genetically important material from Canidae to be saved. In dogs, the oocyte is ovulated when immature rather than mature, as in other species, and the survival rate of spermatozoa is greater within the female tract. By incorporating knowledge of canine reproductive physiology and work on in vitro culture in other mammals, some important achievements have been made. Sperm capacitation, induction of the acrosome reaction, maturation of canine oocytes and fertilization have all been achieved in vitro. Embryo culture has proven more difficult, with only two studies reporting success. Cryopreservation of spermatozoa has been perfected and is used routinely when transporting semen for artificial insemination. However, improvement in embryo culture techniques and development of oocyte and embryo freezing are required. This work in the domestic model may lead to development of a gamete-banking programme to safeguard the future of endangered canine species.

Acrosome Reaction↗

Fundamental cryobiology of reproductive cells and tissues.

During the last half of the 20th century there have been considerable advancements in mammalian reproductive technologies, including in vitro production of pre-implantation embryos and embryo sexing, and even cloning in some species. However, in most cases, management of non-cryopreserved reproductive cells (i.e., spermatozoa or oocytes) and tissues (i.e., testicular tissue or ovarian tissue) is problematic due to difficulties in donor-recipient synchronization and the potential for transmission of infectious pathogens, which cumulatively limits widespread application of these techniques. Therefore, there is an urgent need for the development of optimum cryopreservation methods for reproductive cells and tissues from many species. Today frozen-thawed spermatozoa and embryos have become an integral component of animal agriculture, laboratory animal genome banking, and human sperm banking and infertility programs. However, although widely implemented, the protocols currently used to cryopreserve bull sperm, for example, are still suboptimal, and cannot readily be extrapolated to other species' sperm. Similarly, embryo-freezing protocols successfully used for mouse and cattle have yielded little success when applied to some other species' embryos, or to a related cell type, oocytes. To date, with the exception of mouse oocytes, almost all mammalian species' oocytes studied have proven very difficult to successfully cryopreserve. Currently, there is a growing interest to understand the underlying cryobiological fundamentals responsible for these low survival rates in an effort to develop better cryopreservation methods for oocytes. Additionally, there is growing interest in developing technologies for the optimal isolation and cryopreservation of the earliest stage of male (spermatogonia, spermatids) and female (primordial follicle) germ cells, with subsequent maturation to the desired stage in vitro. Female gamete maturation, fertilization, and embryo development entirely under in vitro conditions from primordial follicles has been achieved in mice, however techniques for this and other species are still very early in their development. Furthermore, with the recent advances made in intracytoplasmic sperm injection (ICSI), and gamete isolation and maturation, close attention has been given to cryopreservation of gametes in the form of gonadal tissue (i.e., testicular tissue and ovarian tissue) containing various developmental stages of male (spermatogonia, spermatids, and spermatozoa) and female (primordial, secondary) germ lines.

Animals↗

Present concept of unexplained infertility.

Despite improvements in both diagnostic assessment and treatment of infertile couples, many couples still have no explanation for their infertility. Unexplained infertility (the failure to conceive of a couple in whom no definitive cause for infertility can be found) has an incidence of 10-20% in all infertile couples. The incidence varies with the population studied and with the criteria used. Unexplained infertility is not an absolute condition but rather a relative inability to conceive, and many of these couples may conceive without treatment. The treatment options for unexplained infertility are several and the treatment results are promising. Expectant management can be recommended if the woman is under 28-30 years of age and the infertility duration is less than 2-3 years. In vitro fertilization (IVF) has revolutionized the treatment of infertile couples, as well as profoundly increasing the basic understanding of human reproduction. IVF can be used as both a diagnostic and a therapeutic tool in couples with unexplained infertility. The pregnancy rates with IVF are good, at 40% per treatment cycle. In addition, the outcome of pregnancies among women with unexplained infertility is generally comparable to that of spontaneous and other pregnancies using assisted reproductive technologies.

Adult↗

The issue of sex selection in Turkey.

In accordance with a recent decision of the High Health Council, which is the highest advisory Council of the Ministry of Health, and following 6 months of debate, the clinical application of sex selection methods when there are no medical indications has been restricted in Turkey. The participants of the debate were the Turkish counterparts of Dr R.J. Ericsson, who is the owner of the patent of the sperm separation method, the General Directorate of Mother and Child Health and Family Planning, the Ethical Committee of the Turkish Medical Association, the Legal Consultancy of the Ministry of Health and the whole community through the press and television programmes. Many reports concerning sex selection were prepared that were opposed to the application of the Ericsson method when there were no medical indications, depending on ethical and technical considerations. The debate also induced ethical discussions about other related subjects, such as recent improvements in reproductive technologies, prenatal diagnosis and the Human Genome Project.

Bioethics↗

Reproductive parameters of male dromedary and bactrian camels.

Functional anatomy of male reproductive organs and reproductive physiology of dromedary and bactrian camels are quite similar except for some differences in the seasonal pattern of reproductive events: left testes bigger than right; scrotum not pendulous; vas deferens very convoluted with 2 mm diameter; prostate divided into 2 parts by septum, with many ducts; bulbourethral (Cowper's) glands well developed and seminal vesicle absent; fibroelastic penis has "prescrotal" sigmoid flexure and the glans resembles crochet needle; triangular-shaped prepuce directed posteriorly to open to the rear, and can move cranially or caudally during erection or urination, respectively; semen ejaculate, 1-12 mL in volume with little gelatinous material, coagulates and liquifies within minutes; total sperm/ejaculate 6 x 10(9) sperm/mL; semen contains PGE1, PGE(2x,LH), estradiol progesterone/other metabolites; semen collected by AV used for bulls with long copulation time; ovulation induced 36-48 h after mating or insemination; sperm of a short life of 1-6 h at 0.4 degrees C, is prolonged in presence of mucopolysaccharide gel; fresh semen inseminated. Topics of future research on endocrinology of reproduction, gonadal physiology, semen biology assisted reproductive technology, and gene transfer to germ cells of camels are outlined. The prevention and control of STD is an important component of camel stud management to improve reproductive performance in this species.

Animals↗

Rewards and risks of human embryo creation: a personal view.

Understanding how a single cell, the fertilised egg, can develop into all the tissues in the body has been referred to as one of the two great problems facing biology; the other is how the brain works. To be working on the early human embryo is a reward in itself. To see such knowledge applied to improve the lives of infertile couples provides special rewards. There are considerable technical challenges in these activities due to the paucity of experimental material, particularly in the human. A major intellectual challenge is to understand the mechanisms that regulate early embryo development, especially the role of signal molecules intrinsic to the embryo and those that are maternally derived. Central to this issue are notions of embryo autonomy and plasticity; the extent to which the same genotype can give rise to different phenotypes in response to environmental perturbations and the need to discover how severe such changes have to be to induce irreversible changes that can compromise the health of the offspring. Research areas that could be fruitful include stress-induced causal effects, cell signalling and the concept of 'quiet metabolism'. Managing assisted conception practices and their associated risks requires a regulatory framework to ensure the safety and efficacy of the new technologies. However, there is a danger of over-regulation, a cultural phenomenon characterised by a rise in audit and decline in trust. The challenge is to devise regulation in assisted reproduction technologies proportionate to the risks. The ultimate rewards will come from understanding how the human genome operates in functional terms. The ideal system in which to study this is the human blastocyst, an autonomous, functional group of mammalian cells.

Blastocyst↗

Fertilization of IVF/ICSI using sibling oocytes from couples with subfertile male or unexplained infertility.

The significance of the performance of conventional in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) using sibling oocytes from couples with subfertile male or unexplained infertility was evaluated. A total of 410 sibling oocyte cumulus-corona complexes (OCCC) from 21 couples with subfertile male (group A) and 11 unexplained infertile couples (group B) were randomly divided, in order of retrieval, into two groups inseminated either by conventional IVF or by ICSI. The treatment outcomes and the influence of infertility factors on fertilization in each group were compared. The results showed that although the two pronuclear (2PN) fertilization rate per injected sibling oocytes was significantly higher after ICSI (group A: 68.2% +/- 28.8%; group B: 66.2% +/- 24.9%) than after conventional IVF (group A: 41.8% +/- 32.7%; group B: 40.1% +/- 22.1%), the other variables studied included: the fertilization rates of per allocated sibling oocytes IVF/ICSI, the fertilization rates of sibling oocytes IVF/ICSI after excluding failed IVF fertilization cycles, as well as the cleavage rates of normal fertilization were not statistically significant (P>0.05). Similarly, though the total fertilization failure rate in the IVF group (group A: 42.9%; group B: 36.4%) was significantly higher than in the ICSI group (group A: 4.8%; group B: 0), we did not cancel cycles due to the normal fertilization of sibling oocytes. Embryo transfer was possible in all 32 couples. There were 10 clinical pregnancies in the two groups. We also discovered a possible association between some semen parameters and sperm functions of group A, and women age and duration of infertility of group B and fertilization. It is suggested that adoption of the split IVF/ICSI technology in the above cases may help eliminate fertilization failures. This is also a useful method to investigate the effect of single factor on the employment of assisted reproductive technology.

Embryo Transfer↗

In vitro capacitation of bovine spermatozoa: role of intracellular calcium.

The development of successful methods of in vitro fertilization for bovine oocytes has advanced the bovine as a model for reproductive technology. The discovery of heparin as a capacitating agent has made it possible for investigators to have an inexpensive, readily available supply of bovine gametes for experimentation in reproductive biotechnologies such as gene transfer and cloning. The central event that mammalian sperm must undergo before being able to fertilize an oocyte is capacitation. Although we have methods which lead to efficient in vitro fertilization, we still lack understanding about the molecular mechanisms of capacitation. While numerous events occur during capacitation, it appears that regulation of intracellular Ca2+ (Ca(i)) is one of the most important. We found that the influx of Ca2+ into sperm during the first 2 hours of incubation is critical to heparin-induced capacitation. This is a period during capacitation when Ca(i) has not yet increased. We propose that during capacitation, the initial influx of Ca2+ into sperm is used to fill an intracellular Ca2+ store located in the acrosome. We found that thapsigargin, an inhibitor of an acrosomal Ca2+-ATPase, can stimulate capacitated sperm to acrosome react, trigger the opening of a store-operated calcium channel in the plasma membrane and has greater effects on capacitated sperm compared to noncapacitated sperm. An increase in intracellular Ca2+ was also detected in the anterior sperm head during capacitation, suggesting the loading of the acrosome with Ca2+. These observations may be important in the development of new methods for capacitation and understanding the death of sperm after cryopreservation.

Aniline Compounds↗

Medical resource allocation: rationing and ethical considerations, Part II.

The proliferation of medical technology during the past decade has doubtless surpassed that of any other recent period. We have witnessed and are continuing to witness rapid advances in human genetic engineering, reproductive technology, and biomedical intervention in the life process. Our population has benefitted from this technology as a result of its ability to extend the life of individuals, particularly the elderly sector of our society. This technological proliferation has caused philosophers, physicians, engineers, and policy strategists to focus upon questions of ethics and mortality relating to their application. In approaching the ethics of rationing, consideration must be given to both the deontological concepts of the individual and the utilitarian principles of societal preservation. This article continues a discussion of the issues of resource allocation that was begun in the February 1994 issue of Physician Executive.

Advance Directives↗

Arising from the dead: challenges of posthumous procreation.

The medical capabilities derived from modern reproductive technology, such as in vitro fertilization and cryopreservation, have enabled physicians and scientists to intervene in the procreative process in innumerable ways. However, this intervention in the natural reproductive process raises both moral and legal concerns. In this Article, Professor Schiff explores some of the conflicts that may result when an individual or couple elects to cryopreserve gametes or embryos and subsequently, one or both of the contributors dies, or when gametes are harvested from a dead body. This Article will specifically address the moral and legal responses to circumstances where the decedent has either clearly expressed opposition to posthumous use of the reproductive material or else the decedent's intent regarding posthumous use of the material is ambiguous. By discussing philosophical and moral positions relating to personhood and the body and analyzing legal issues such as reproductive choice and organ donation, Professor Schiff creates the necessary format to examine and recommend the proper legal treatment of this controversial aspect of posthumous procreation.

Cryopreservation↗

The genetics of male infertility.

PURPOSE: We provide an up-to-date summary of the genetic aspects of male infertility. MATERIALS AND METHODS: The literature on male infertility was extensively reviewed. RESULTS: Genetic defects are associated with a variety of clinical presentations by the infertile man ranging from gonadotropin-releasing hormone deficiency to spermatogenic failure to obstructive azoospermia. Microsurgery and micromanipulation of gametes make it possible for many of these men to father children. However, with each successive breakthrough in treatment of male infertility there is an increased risk of transmitting genetic abnormalities to the progeny. CONCLUSIONS: Transmission of genetic defects through assisted reproductive techniques can have serious long-term implications. Assisted reproductive techniques should not be initiated in men with a possible or known genetic cause of infertility without prior genetic counseling and risk assessment. Clinicians and researchers involved in reproductive medicine must recognize that, although these techniques have revolutionalized the treatment of male infertility, they have the risk of passing genetic abnormalities to the progeny. Therefore, researchers must proceed cautiously with development and application of assisted reproductive technologies to avoid creating future generations of genetically abnormal individuals. The first step in accomplishing this goal is through an increased understanding of the genetic basis of male reproductive failure.

Chromosome Aberrations↗