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Endometrial abnormalities in infertile women.

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.

Adult↗

Application of ICSI for cryptorchid therapy.

Recent advances are provided in assisted reproductive technology and application of ICSI as treatment for infertile patients with previous cryptorchidism. Fertility rates were 25-81% and 8-48% in patients with unilateral and bilateral cryptorchidism, respectively. With the advent of assisted reproductive technology, pregnancy was not possible without sperm. Research in humans has resulted in pregnancy and live births after the injection of haploid germ cells (round spermatids) into the oocytes. In the mouse tetraploid germ cells (primary spermatocytes), nuclei have been injected into oocytes, which undergo meiosis, forming an embryo and live young. In animal models, round spermatids from both cryptorchid and previously cryptorchid testes can initiate normal embryo development when injected into mature oocytes. These cells may be used as substitutes for mature sperm. However, cryptorchidism in humans is often associated with inherent defects of spermatogenesis. With successive breakthroughs in treatment of impaired fertility associated with cryptorchidism, there is an increased risk of genetic abnormalities in the progeny. It is incumbent on clinicians who are involved in reproductive medicine to proceed cautiously with the development and application of assisted reproductive techniques to avoid creating future generations of genetically abnormal individuals.

Cryptorchidism↗

En route to an "instant family": psychosocial considerations.

Societal and cultural norms require that a worthwhile person engage in reproduction and formation of a family. Young adults who postpone childbearing may presume that fertility is granted. When all other measures fail, the use of assisted reproductive technologies is considered the ultimate salvation for these couples. It is highly stressful and may lead to significant negative psychological consequences (loss of self-esteem, confidence, health, close relationships, security, and hope). Assisted reproductive technology may produce multiple pregnancy, which is frequently overlooked or underappreciated by infertile couples. Despite the real risks associated with a multiple pregnancy and birth, infertile patients often express a desperate wish to have twins or triplets, thereby accomplishing an instant family. It is necessary to provide these couples with detailed information on the risks of multiple pregnancy and birth.

Female↗

Effect of ovarian cysts detected on the beginning day of ovulation induction to the success rates in ART cycles.

AIM: In the present study, we examined the outcome of assisted reproductive technology cycles in patients with or without baseline ovarian cysts following gonadotrophin-releasing hormone analogs administration. MATERIALS AND METHODS: Three-hundred and fifty-six patients who had undergone assisted reproductive technology treatment were enrolled in the study. The patients, all of who had undergone cyst aspiration prior to ovarian stimulation, were grouped into two groups according to the absence or presence of ovarian cysts. These two groups were compared on the basis of the clinical pregnancy rates, the baseline E2 levels, the total follicle stimulating hormone ampules used, the total number of days of induction, the maximum E2 levels, the number of oocytes retrieved, the fertilization rates and the number of embryos available for transfer per controlled ovarian hyperstimulation cycle. RESULTS: The number of ampules used for induction was significantly higher in the cyst group 37.2 +/- 13.0, 32.1 +/- 11.7, respectively, (P = 0.001). The number of total induction days was also longer in the cyst group 9.7 +/- 2.2, 8.9 +/- 1.6, respectively, (P = 0.001). There was no difference between the mean E2 levels measured on the human chorionic gonadotropin administration days (P = 0.339). There was also no difference in terms of the number of oocyte retrieved (P = 0.846). The number of embryos transferred did not differ statistically between the groups (P = 0.233). Finally, there was no significant difference between the groups according to the clinical pregnancy rates 25.3%, 30.7%, respectively, (P = 0.218). CONCLUSION: Baseline ovarian cysts have a negative impact on the quality of ovarian hyperstimulation procedure; however, they have no negative effect on the pregnancy rates in IVF cycles.

Adult↗

Diagnostic laparoscopy in infertility: a retrospective study.

STUDY OBJECTIVE: To evaluate the role of laparoscopy in the diagnosis and therapy of infertility. DESIGN: Retrospective study. SETTING: Academically affiliated reproductive endocrinology practice. PATIENTS: One hundred seventy patients. INTERVENTION: Diagnostic/therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: One hundred seventy infertile patients underwent diagnostic laparoscopy between 1996 and 2000 in our clinic, and 109 of them were seen at follow-up more than 1 year after laparoscopy. Of the 109 patients, 77 (70.6%) were treated with assisted reproductive technology, such as in vitro fertilization-embryo transfer, and 32 (29.4%) were treated with conventional procedures. Of the 109 patients, 68 (62.4%), including 39 (50.6%) of the 77 treated with assisted reproductive technology and 29 (90.6%) of the 32 treated with conventional procedures, became pregnant. Of the 68 patients who became pregnant, 49 (72.1%) of them conceived within 1 year after laparoscopy. CONCLUSION: Laparoscopy is an important procedure in the treatment of infertility.

Embryo Transfer↗

Public health policy and infertility.

In assisted reproductive technology, three main areas are relevant from a health policy perspective: first, the technical excellence of the services rendered; second, a licensing and monitoring system to control all practitioners and the premises in which they work; and third, legislation to avoid abuse, prevent possible damage to the mother and the child and outlaw techniques unacceptable in a given cultural setting, including mechanisms to ensure the adherence by all to ethical and deontological principles. No one refuses the need to ensure that services offering assisted reproductive technologies adhere to technical excellence and everyone agrees that technical guidelines should exist and should be thoroughly enforced. When it comes to legislating about assisted reproductive techniques and, more specifically, to ruling in favour of limiting the use of existing technology to certain groups and not to others, or to ban altogether individual methods, views are sometimes totally divergent. In countries where legislation is fairly liberal, usually both physicians and the public view legislation with favour; conversely, where a number of restrictions exist, many complain that legislation impairs their ability to offer proper services. The solution seems to be a simple, well-defined, legislative act setting clear principles and providing for the creation of an Authority capable of resolving the myriad of individual problems that invariably arise from applying assisted reproductive techniques. Homo sum et nihil humanum a me alienum puto I am a human being and therefore cannot consider alien to me anything that helps another human being.

Female↗

Applications of emerging technologies to the study and conservation of threatened and endangered species.

Sustaining viable populations of all wildlife species requires the maintenance of habitat, as well as an understanding of the behaviour and physiology of individual species. Despite substantial efforts, there are thousands of species threatened by extinction, often because of complex factors related to politics, social and environmental conditions and economic needs. When species become critically endangered, ex situ recovery programmes that include reproductive scientists are the usual first line of defence. Despite the potential of reproductive technologies for rapidly increasing numbers in such small populations, there are few examples of success. This is not the result of a failure on the part of the technologies per se, but rather is due to a lack of knowledge about the fundamental biology of the species in question, information essential for allowing reproductive technologies to be effective in the production of offspring. In addition, modern conservation concepts correctly emphasise the importance of maintaining heterozygosity to sustain genetic vigour, thereby limiting the practical usefulness of some procedures (such as nuclear transfer). However, because of the goal of maintaining all extant gene diversity and because, inevitably, many species are (or will become) 'critically endangered', it is necessary to explore every avenue for a potential contributory role. There are many 'emerging technologies' emanating from the study of livestock and laboratory animals. We predict that a subset of these may have application to the rescue of valuable genes from individual endangered species and eventually to the genetic management of entire populations or species. The present paper reviews the potential candidate techniques and their potential value (and limitations) to the study and conservation of rare wildlife species.

Animals↗

Embryo afterloading: a refinement in embryo transfer technique that may increase clinical pregnancy.

OBJECTIVE: Given the importance of ET technique during assisted reproductive technology cycles, we evaluated the effect of embryo afterloading subsequent to placement of the ET catheter on pregnancy rates vs. a standard direct ET. DESIGN: Retrospective cohort analysis. SETTING: University-based assisted reproductive technology program. PATIENT(S): Patients undergoing a fresh nondonor day 3 ET by a single provider over a 1-year period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): One hundred twenty-seven patients met inclusion criteria, and the overall pregnancy rate was 46.5%. There was no difference between the two groups with respect to age, basal FSH, or number of embryos transferred. The ET method used was at the discretion of the provider. There was no difference between the two groups in the presence of blood on the transfer catheter. However, there were significantly more transfer catheters with mucus contamination in the direct transfer group (25.58% vs. 5.95%). The clinical pregnancy rate in the group with ET using the afterloading technique was higher than in the direct ET group (52.4% vs. 34.9%). CONCLUSION(S): There was a trend toward an increase in pregnancy rate when an embryo afterloading technique was used. A prospective randomized trial is needed to examine this issue.

Adult↗

[Obstetrical management of triplets. A series of forty five cases].

OBJECTIVE: To evaluate management of triplet pregnancies. METHODS: A retrospective study of 45 triplet pregnancies which occurred spontaneously or after assisted reproductive technologies. All were managed by the same obstetrical and pediatric team. Obstetrical data were collected. RESULTS: Major etiologies were fertility drugs and in vitro methods (66%). Mean maternal age as 30 years, higher with assisted reproductive technologies (p < 0.05). Risks of chorioamniotitis, preeclampsia and anemia were respectively 4.4%, 13.3% and 70%. Triplets had a 100% prematurity rate and mean gestational age was 33.6 weeks; 22.2%, 51.1% and 64.4% delivered before respectively 32, 34 and 35 weeks of gestation. Triplet had a 91% cesarean section rate. CONCLUSION: Triplet pregnancies present a high risk of prematurity and infertility specialists have to be vigilant in the use of fertility drugs. Their management requires early reduced maternal physical activity.

Adult↗

The role of paf in embryo physiology.

Embryo-derived paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is produced by de novo synthesis. This synthesis commences soon after fertilization and persists throughout the preimplantation phase. Paf is produced and released by the embryos of all mammalian species studied to date. Its release from the embryo involves binding to extracellular albumin in a manner that protects paf from enzymatic degradation. Released paf causes a range of alterations in maternal physiology, including platelet activation, changes in oviductal, endometrial and maternal immune function. Paf also acts in an autocrine fashion as a trophic/survival factor for the early embryo. In vitro, supplementation of culture media with paf improves embryo development. Embryo-derived paf's autocrine actions are transduced by 1-o-phosphatidylinositol-3-kinase, which induces characteristic calcium transients within the early embryo. The calcium transients require both the influx of external calcium and release of inositol trisphosphate-dependent internal calcium stores. Buffering these transients compromised embryo development in a manner that was reversed by exogenous paf. Assisted reproductive technologies compromise the production of paf by some embryos and retard the expression of the paf receptor. This deprivation of paf's action is one of the factors limiting the survivability of embryos produced by assisted reproductive technologies. Paf is one of several autocrine and paracrine trophic/survival factors that act on the early embryo. These factors probably act cooperatively and may, to some degree, be mutually redundant. As the earliest-released and the best-described embryotrophin, paf provides an important exemplar for understanding the role of ligand-mediated trophic support of the early embryo.

Animals↗

Ethical issues of fertility and reproduction.

How reproductive technologies are used has consequences not just for immediate users but for others as well. This article discusses issues that should be taken into consideration in coming to decisions about whether or not it is appropriate to use a particular reproductive technology, or whether to use a technology in a particular way.

Commodification↗

Non-genetic mothers and their own children: infertility and IVF donor birth.

Over the 1980s in Western societies which have used new reproductive technologies, there has been intense argumentation about connected philosophical, ethical and economic issues. This research on I.V.F. donor egg (i.e. 'non-genetic') motherhood is based on qualitative data from partial life histories of twelve women having children by this technology through a Melbourne infertility programme. Methodology, interpretation, and discussion place it within both critical social and feminist personal identity theoretical frameworks. None of the respondent women but all except one of their respective partners are the biological parents of a total of ten children already born at the data collection stage, and in three well-established pregnancies. Two-thirds of the respondents used 'unknown' donor ova. 'Known' donors were typically the recipients' sisters. Many of these Australian births represent world 'firsts' in medical technical applications. In biographical accounts, the focus was on experiences of social pressure towards parenthood, of infertility and medical treatment, and attitudes of openness or secrecy about using donated ova. While socially and technologically acquired parenthood added a highly-desired dimension to their social identities, a sense of loss appeared to persist in most of the women's personal identities. Where a policy of secrecy towards relatives and friends about use of reproductive technology and gamete donation was maintained, this loss was reinforced by a feeling of social isolation.

Australia↗

What regulations for preimplantation genetic diagnosis?

PURPOSE: To discuss the qualifications of personnel involved in either (a) embryo biopsy/slide fixation, (b) performance of preimplantation genetic diagnosis-specific assays, or (c) interpretation of findings and results from such studies. METHODS: Illustrate similarities and differences between the qualifications and licensing requirements for personnel involved in high complexity testing in other laboratory specialities, such as microbiology or endocrinology. RESULTS: Parallels can in fact be drawn between specific personnel certification and licensing requirements for reporting test results following preimplantation genetic testing and those for other clinical specimens submitted for testing. CONCLUSIONS: Assisted reproductive technology programs generally do not have personnel certified in cytotechnology or clinical genetics. Programs that perform the actual interpretation of specimens submitted for evaluation by fluorescent in situ hybridization will have to have supervisory personnel certified to perform such interpretations to ensure the level of quality control and assurance now afforded in centers for assisted reproductive technology.

Female↗

Five decades of progress in management of the infertile couple.

OBJECTIVE: To review milestones in the care of the infertile couple over the past five decades. DATA RESOURCES: All issues of Fertility and Sterility were reviewed beginning with the first issue published in 1950 through volume 61, number 1 (January 1994). Other significant articles from the literature were reviewed as identified by directed Medline searches. RESULTS: This historical review gives the reader a sense of the evolution of modern reproductive technology--how the past has shaped the present--through the development of modern surgical techniques, methods of ovulation induction, laparoscopy, ultrasound, endocrine assays, in vitro fertilization, cryopreservation of sperm and preembryos, and microscopic procedures on gametes and preembryos. CONCLUSIONS: The remarkable capabilities of modern reproductive technologies are only possible because of the culmination of decades of innovative research.

Female↗

Infertility due to antisperm antibodies.

Immunoinfertility is an important problem, involving a significant number of infertile couples. Although the presence of antibodies on sperm has better prognostic value than those in serum or seminal plasma, it may not be the sole authentic evidence of immunoinfertility. Infertility from antisperm antibodies is likely only when they bind to a relevant sperm antigen involved in a specific fertility function. The variance in functional deficits seen in immunologic infertility is most likely related to antibodies directed at different sperm antigens or different class, subclass, or isotypes. Antibodies to FA-1 seem to be of significant importance in human immunoinfertility. In approaching couples with infertility, a high index of suspicion for antibodies is necessary to avoid misdiagnosis. In the optimal situation, all semen analyses should be screened for sperm-bound antibodies, but if this is impractical, testing should be performed on high-risk individuals (Table I). In couples in which the man has sperm-bound antibodies, and in whom there is no identifiable female factor, treatment should be instituted. Most treatments for immunoinfertility have been disappointing because of poor results, adverse effects, or high cost. Corticosteroid therapy has shown some promise in published reports (mostly poorly designed studies), but increase in pregnancy rate is modest and adverse effects may be significant. In our opinion, informed consent should be documented prior to institution of corticosteroid therapy, and subjects should be closely monitored. Advanced reproductive technologies offer a higher safety profile, and, with increasing technology, higher pregnancy rates. We recommend progressing from "low-tech" procedures, such as IUI and reserving the higher level procedures, such as IVF and ICSI, for those couples in whom pregnancy does not occur. The highest level reproductive technologies give the best current prospects for pregnancy in patients with this difficult problem but also are invasive and costly. It is hoped that further work in the laboratory will give rise to newer, safer, and less expensive effective treatments in the very near future.

Antigens, Surface↗

Medical treatment to improve sperm quality.

Approximately 30% of cases of couple infertility are due to a male factor. Several conditions can interfere with spermatogenesis and reduce sperm quality and production. Treatable conditions, such as hypogonadism, varicocele, infections and obstructions, should be diagnosed and corrected, but many aspects of male factor infertility remain unclear. Various agents have been used in the attempt to increase the fertility potential of subjects with idiopathic oligoteratoasthenozoospermia. The rationale of medical treatment to improve sperm quality in these subjects has been questioned by the introduction of assisted reproductive technologies. However, there is now growing awareness of the importance of good quality spermatozoa for embryonic development and higher birth rates. Confounding factors in assessing the efficacy of male infertility treatments have erroneously inflated the superiority of assisted reproductive technologies over conventional approaches. A systematic review is given of relevant randomized controlled trials and effects on semen parameters. The analysis reveals that although results are heterogeneous, gonadotrophins, anti-oestrogens, carnitine and trace elements may be beneficial in improving sperm quality, although their effect on pregnancy rate remains controversial. The most common drug regimens are compared and an estimate of the results expected from these treatments provided.

Antioxidants↗