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Fertility in patients with multiple sclerosis: current knowledge and future perspectives.

The issue of fertility in patients with multiple sclerosis (MS) has not been exhaustively studied. Epidemiological data have suggested that spontaneous fecundity might be reduced; several endocrine and sexual disturbances potentially interfering with reproduction have been evidenced in MS patients of both sexes. Moreover, some medical treatments used in MS (e. g., mitoxantrone, cyclophosphamide) may exert detrimental effects on spermatozoa as well as on oocytes, leading to early impairment of fertility. This review illustrates the factors potentially interfering with fertility in MS and discusses the therapeutic tools that may be used to promote fertility in these patients. The safety of hormonal therapies in MS is also examined. The current applications of assisted reproductive technology (ART) are discussed, including in vitro fertilisation (IVF) techniques. Currently available methods to preserve fertility in patients that undergo cytotoxic treatments by means of sperm/oocyte cryostorage or by ovarian fragment cryopreservation and autografting are considered.

Antineoplastic Agents↗

Improved pregnancy rate after transfer of embryos grown in human fallopian tubal cell coculture.

OBJECTIVE: To evaluate the embryonic behavior in vitro and the pregnancy and implantation rates of embryos grown in a human ampullary cell coculture system. DESIGN: In a prospective study, two pronuclei embryos were cultured on human ampullary feeder layers up to the two to six-cell and blastocyst stages and replaced either as tubal, uterine, or sequential transfers. SETTING: Assisted reproductive technology program in a university-based hospital. PATIENTS: Fifty women with a mean age of 35.6 years who went through a single coculture cycle. Thirty of the patients were admitted for in vitro fertilization (IVF) and 20 for tubal embryo transfer (TET). RESULTS: The overall clinical pregnancy rate (PR) for all 50 patients was 44% per cycle (IVF, 37%; TET, 55%) and the implantation rate was 31.8% (IVF, 31.0%; TET, 32.6%). Sixty-eight percent of pregnant patients were over 35 years, and 68% had two previously failed assisted reproduction cycles. Five of 9 patients who received sequential transfers became pregnant. Three of the 22 pregnancies aborted (2 after sequential transfer), and there was one ectopic. Overall, 88% of two to six-cell stage embryos were of good quality. CONCLUSIONS: The human ampullary coculture system produces better quality embryos, increased numbers of blastocysts with improved PRs and implantation rates. The beneficial effects of the feeder layer may be through the release of embryotrophic factors and detoxification of the medium by the cells. Coculture is a new concept in assisted reproduction and has tremendous potential in boosting conception rates by mimicking the in vivo environment.

Adult↗

Fetus in Germany: the Fetus Protection Law of 12.13.1990.

The "Fetus Protection Law" (Embryonenschutzgesetz ESchG) regulates the abusive use of reproductive techniques, the use of human embryos and the choice of sex. The Bundestag has singled out certain practices as being abusive, prohibited them and put criminal sanctions on them. Individual exemptions from criminal prosecution are made in favour of the surrogate mother who is to be the target of an assisted procreation and the foster-father. The ESchG represents a snapshot of current views on current practices in reproductive medicine. And therefore the ESchG will be rendered obsolete by newly created reproductive technologies if legislation does not adapt the law to these changes.

Abortion, Induced↗

Complications of pregnancy in infertile couples: routine treatment versus assisted reproduction.

Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for the following complications: pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

Congenital abnormalities in children born after assisted reproductive techniques: how much is associated with the presence of infertility and how much with its treatment?

Although there is increasing evidence to link couples with infertility undergoing all assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI), and congenital abnormalities, the reasons remain unclear. Much evidence suggests that infertility itself might be a risk factor, and further long-term follow-up studies involving different possible control groups will help determine whether these abnormalities are directly related to treatment.

Child↗

An evidence-based evaluation of endometriosis-associated infertility.

Although endometriosis is associated with infertility, a clear causal relationship has yet to be established, unless adhesive disease is found. Despite this indirect association, multiple theories have been promulgated and studies are currently underway to investigate theoretic pathogenetic mechanisms. The data regarding the treatment of endometriosis-associated infertility are limited and conflicting; however, some general preliminary conclusions can be drawn. It seems that, with early-stage disease, surgical treatment increases pregnancy rates. Using the US Preventive Services Task Force classification scheme, the evidence in support of this finding is of the highest quality, or level I. Surgical treatment for moderate and severe disease also confers benefit, although the evidence in support of this treatment is of lesser quality, level II-3 by the scheme. Medical treatment, particularly if it induces an anovulatory state, has no benefit and may delay fertility. This evidence is again of the highest quality, with a classification of level I. Although assisted reproductive technologies are of benefit regarding fertility for women with endometriosis, the IVF evidence is inconclusive, with both treatments being evaluated by at least one randomized, controlled trial conferring a level I classification to the evidence. It is unclear at this time whether endometriomas have an impact on IVF outcome. The evidence consists of only a few lower-quality studies, with a classification level of II-2. Despite the haziness of current insight into the treatment of endometriosis-associated infertility, well-designed clinical trials and basic mechanistic investigations are underway in many reproductive medicine centers. As the data from these scientific inquiries emerge, clinicians will have a clearer view of effective treatment regimens for endometriosis.

Adolescent↗

Intrafollicular insemination for the treatment of infertility.

The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.

Adult↗

Variations in the maternal age effect on twinning rates: the Nordic experience.

Maternal age is the most important nongenetic factor influencing the twinning rate. Every study of the effect of other factors should consider the age distribution of the mothers. Besides standardizing techniques, the age-specific twinning rates are analyzed. Especially, the slope of the regression line is considered when the age-specific twinning rates are regressed against maternal age. How well the maximum age-specific twinning rate measures the variation in the maternal age effect is also studied. The two measures, which are strongly correlated, give consistent results. The proposed methods are applied to data from Finland (1866 to 2003) and Denmark (1855 to 2000). Comparisons with Sweden (1861 to 2000) and Norway (1855 to 2003) are also made. In general, marked decreasing trends in the twinning rates are discernible up to the middle of the 20th century. In Sweden the decline starts around the beginning of the 20th century and is stronger than in Denmark and Norway. The decrease in the twinning rate for Finland, which up to World War II was rather isolated, sets in around the middle of the 20th century and is not as strong as in other Nordic countries. After the minima around 1980, strong increasing trends are noted. This is mainly caused by the influence of the artificial reproduction technologies and particularly the use of fertility-enhancing drugs on the commonly noted dependence between maternal age and the twinning rate. Similar temporal trends can be observed in the slopes of the regression line and in the maximum age-specific twinning rates.

Adolescent↗

Infertility evaluation and treatment according to Jewish law.

The Jewish attitude toward infertility can be learned from the fact that the first commandment of God to Adam was "be fruitful and multiply". When evaluating an infertile couple according to the Halakha (Hebrew law), one should first evaluate the female factor. If pathology is found, one may proceed to investigate the male factor, inadequate or abnormal production, ejaculation, or deposition of spermatozoa. The basic fact that allows in vitro fertilization (IVF) and embryo transfer (ET) to be considered in the rabbinical literature at all is that the oocyte and the sperm originate from the wife and the husband, respectively. For many centuries Jewish religious authorities have discussed the principle involved in artificial insemination from a donor. The discussions are based on ancient sources in the Talmud and the codes of Jewish law is prohibited for a variety of reasons e.g. incest, lack of genealogy, and the problem of inheritance. In the case of egg donation the problem that arises is who should be considered the mother, the donor of the oocyte or the one in whose uterus the embryo develops, the one who gives birth. Jewish law states that the child is related to the woman who finished its formation, the one who gave birth. The Jewish religion does not forbid the practice of surrogate motherhood in the case of full surrogacy. From the religious point of view, the child will belong to the father who gave the sperm and to the woman who gave birth. Creating and inducing a preimplantation in embryo in vitro for fertility research should be allowed if there is a real chance that the sperm owner may benefit and have a child as a result of this research. Nowadays, assisted reproductive technology is a common practice in the treatment of infertility. Nevertheless, different religious arguments of the world's religions impose limitations on the therapeutic approach to infertility.

Embryo Research↗

Splitting embryos on the slippery slope: ethics and public policy.

Neither the George Washington University embryo splitting experiment nor the technique of embryo splitting itself has ethical flaws. The experiment harmed or wronged no one, and the investigators followed intramural review procedures for the experiment, although some might fault them for failing to seek extramural consultation or for not waiting until national guidelines for research on preembryos were developed. Ethical objections to such cloning on the basis of possible loss of individuality, possible lessening of individual worth, and concern about potential harm to the resulting children are discussed and challenged, as are objections to the creation of embryos for the purpose of genetic diagnosis. Many of the ethical questions raised by the George Washington experiment are similar to those posed by existing reproductive technologies that allow the simultaneous production of several embryos. A multidisciplinary group should consider whether regulation of cloning is needed, and laws should be enacted to prohibit a commercial market for all frozen embryos.

Attitude↗

Conceiving a child to save a child: reproductive and filial ethics.

I conclude that Mary and Abe's decision to conceive a child to save a child does not impose harm on persons or on relationships in the family. Nor does it evince a lack of respect for the child they have conceived. The ethical guidelines that support this conclusion can now be summarized. First, actions should not depersonalize or otherwise endanger personal relationships. Second, although ideally personal relationships are initiated and continued for their own sake, after a personal relationship has been established and sustained the motives for establishing it recede in importance. Third, the requirement of honesty looms especially large in the context of personal relationships. Fourth, privacy protects personal relationships in the family from intrusion by the state. Fifth, even if those with whom we stand in personal relationships are not fully rational or self-conscious, we should treat them with respect. Finally, persons often are called upon to make greater sacrifices in personal relationships. These principles represent only the barest beginnings of an ethics for filial relationships. Nonetheless, they mark progress in the direction of developing a more complete account. We should not suppose that ethics in the family always will be spontaneous or "natural". Over a century ago, Mill warned that nature and natural are "one of the most copious sources of false taste, false philosophy, false morality, and even bad law". Especially in the wake of medical advances, such as recombinant DNA and new reproductive technologies, the complexity of filial ethics will only increase. The demographics of an aging society will add further complexity to filial contexts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fertility options in young breast cancer survivors: a review of the literature.

PURPOSE/OBJECTIVES: To describe the impact of treatment on fertility, discuss fertility-sparing options available for women with breast cancer, and explore pregnancy subsequent to breast cancer. DATA SOURCES: Published research, clinical articles, book chapters, and abstracts. DATA SYNTHESIS: The risk of amenorrhea associated with alkylating agents in breast cancer survivors is well known. Fertility-sparing options before, during, and after treatment are possible with the use of assistive reproductive technology. Young breast cancer survivors are concerned about stimulating recurrence with subsequent pregnancy, health during pregnancy, and family matters. CONCLUSIONS: Current data about the effects of treatment on amenorrhea, subsequent pregnancy after treatment, preservation of ovarian function during adjuvant therapy, and management of ovarian failure in young women with breast cancer are important to include in discussions and counseling. IMPLICATIONS FOR NURSING: Young women deserve a thoughtful discussion about their concerns among their multidisciplinary team, including oncology nurses, oncologists, and social workers. Effects of treatment on fertility are well known. Women with fertility concerns should be referred to a reproductive endocrinology team at the time of diagnosis rather than after treatment has ended.

Adult↗

In vitro fertilization and gamete micromanipulation in the lowland gorilla.

PURPOSE: Our purpose was to utilize current reproductive technologies to treat an infertile female lowland gorilla. RESULTS: Following pituitary down-regulation with a gonadotropin releasing hormone agonist and follicular stimulation with human menopausal gonadotropins, transrectal ultrasound-guided aspiration of ovarian follicles yielded nine oocytes. Following failed fertilization with both epididymal and electroejaculated sperm, zona dissection and sperm injection were performed and produced one embryo, which was cryopreserved. Immature oocytes were obtained from ovarian sections and were either cultured in vitro or cryopreserved. CONCLUSIONS: This report demonstrates that in vitro fertilization techniques, including pituitary suppression, ultrasound-guided aspiration, micromanipulation, and cryopreservation, can be used to assist reproduction in the lowland gorilla.

Animals↗

Effect of exogenous gonadotropins on endometrial maturation in oocyte donors.

OBJECTIVE: To determine the effects of controlled ovarian hyperstimulation (COH) on endometrial maturation. DESIGN: Prospective, before and after evaluation of midluteal endometrial biopsies in oocyte donor's spontaneous and subsequent COH cycles. SETTING: Tertiary academic medical center assisted reproductive technologies clinic. PATIENT(S): Nineteen oocyte donors. INTERVENTION(S): Exogenous gonadotropins, endometrial biopsies. MAIN OUTCOME MEASURE(S): Endometrial histology and an immunohistochemical marker of uterine receptivity, the alphavbeta3 vitronectin. RESULT(S): Glandular and stromal dyssynchrony was more common after COH in 16 (80%) of 20 cycles than 6 (30%) of 20 spontaneous cycles (P <.05). Glandular lag was more frequent in COH cycles and unaffected by progesterone administration. The beta3 subunit of the alphavbeta3 vitronectin receptor was present in 9 (45%) of 20 spontaneous and 2 (10%) of 20 COH cycles (P <.05). CONCLUSION(S): Exogenous gonadotropin use in healthy reproductive age women did not result in endometrial evidence of a luteal phase defect. A greater incidence of glandular-stromal dyssynchrony resulted from the use of exogenous gonadotropins. The presence of alphavbeta3 was noted in most endometrial specimens demonstrating in phase glandular maturation. We conclude that endometrial dyssynchrony that results from delayed glandular development most likely represents a normal histologic variant.

Adult↗

Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF.

BACKGROUND: Over the past decade attention has been increasingly focused on the long-term health effects of assisted reproductive technologies (ART), such as IVF, in both women and their offspring. To determine the risk of cancer in children conceived by IVF we used a large population-based historical cohort that was initially designed to examine the risk of gynaecological disorders in women who underwent IVF. METHODS: Children were included in the exposed group if they were conceived by IVF or other related fertility techniques (n=9484). The unexposed group consisted of 7532 children whose mothers were diagnosed with subfertility disorders but who were conceived naturally. All cohort members were asked to complete a mailed questionnaire that inquired about reproductive variables and cancer in the offspring (response rate 66.9%). RESULTS: During an average follow-up period of 6.0 years, 16 cancers were observed in the exposed and unexposed group combined, whereas 15.5 were expected [standardized incidence ratio (SIR) = 1.0; 95% confidence interval (95% CI) 0.6-1.7]. A direct comparison between children conceived after ART and naturally conceived children revealed no increased risk for childhood malignancies [risk ratio (RR) = 0.8; 95% CI 0.3-2.3]. CONCLUSIONS: Despite the small numbers of observed cancer cases, these findings demonstrate that children conceived by ART have no greatly increased risk of cancer during childhood compared with the general population and the internal reference group.

Adolescent↗

[Perfusion systems for hemodialysis].

According to generalized designs and technologies of devices used for extracorporeal blood transport in artificial purification and with due respect to their clinical usage, the modern perfusion systems, whose elements of hemodialysis units, can be classified by: a method of connecting them to the cardiovascular system of the patient, a type of perfusion pumps that are in use, and a technique regulating the extracorporeal perfusion velocity and the pressure at the exchanger inlet. The suggested classifications, structure models and results of research of the functional and technical parameters of perfusion systems showed their unified design principles irrespective of construction peculiarities, which can ensure the unified, reproductive, technological, simple and efficient application of the apparatuses now at the stage of creation.

Blood Pressure Determination↗

Response to article -- 'A critical assessment of the impact of the European Union Tissues and Cell Directive (2004) on laboratory practices in assisted conception' by David Mortimer.

The European Union's Tissues and Cell Directive and the US regulations for tissue banks, both produced in 2004, recognize the need to revise current tissue-processing activities and address related risks of infection. The principle behind these regulations and the Australian and New Zealand, Reproductive Technology Accreditation Committee (RTAC) Code of Practice, produced in 2005, are all similar with an underlying quality management theme. Each of these documents is based on the premise to safeguard public health in the prevention of transmission of infectious diseases via transplanted tissues and cells.

Clinical Laboratory Techniques↗

Pathophysiology of oligoasthenoteratozoospermia: are we improving in the diagnosis?

Male infertility is one of the most common identifiable causes of human reproductive failure. Although considerable progress has been made toward understanding sperm physiology and the biology of gamete interaction, still more work is needed to achieve objectivity and standardization of some of the andrological diagnostic methods used in the clinical setting. More information is needed to definitively establish which tests are more accurate predictors of sperm performance and how they correlate with pregnancy potential following in-vivo and in-vitro interventions. Infertile men can be successfully treated with defined urological and medical therapies or with assisted reproductive technologies. Among the latter, intracytoplasmic sperm injection (ICSI) has become a validated means to overcome multiple sperm deficiencies. However, male infertility remains idiopathic in a large proportion of cases. As a consequence, it is expected that simplified and more cost-efficient therapeutic modalities will be developed as additional basic (cellular-molecular) and pathophysiological/clinical knowledge is gained.

Humans↗