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Diagnostics in assisted human reproduction.

The World Health Organization (WHO) estimates that 50-80 x 10(6) couples in the world are infertile, i.e. 7-15% of all couples of reproductive age (15-45 years old). The term infertility refers to couples who have been unable to conceive children for at least 1 year of regular unprotected intercourse. Although the frequency and origin of infertility varies, approximately 40-60% of the aetiology of infertility in the population studied is due to female causes. The introduction of assisted reproduction techniques, which offer couples the best opportunities for pregnancy, has opened a vast field of knowledge in reproductive biology. The medical history must be taken meticulously, with enough time to obtain the largest possible amount of relevant information. It is recommended that both partners be included in the initial work-up. In recent decades, technological progress has been favoured with the development of a great variety of diagnostic tests. Moreover, a very valuable tool helping to solve this problem has gained strength and is available to everybody - so-called 'evidence-based medicine'. There are three categories in infertility diagnostic tests. The first category includes tests showing a well-established correlation with pregnancy, e.g. semen analysis, tubal patency with hysterosalpingography or laparoscopy, and ovulation detection. The second category includes patients whose results are not consistently related to pregnancy. Here, these tests include sperm penetration assay in the zona-free hamster oocyte, post-coital tests, sperm penetration into cervical mucus, and tests to detect anti-sperm antibodies. The third group includes patients whose tests are not correlated with pregnancy. The relevant tests include endometrial biopsy, the presence of varicocele, and Chlamydia detection tests. Tests for infertility are often expensive. Since these patients are usually anxious and eager and will do almost anything to have a child, care must be taken to avoid exploitation of their hopes with unnecessary procedures. This text now reviews and updates the procedures used to investigate infertility.

Acrosome Reaction↗

How to prevent 'half-bastard' progeny? or An alternative for three-parent babies: two-parent babies through transplantation of sperm mitochondria.

Body development and activity depend on the level of internal energy generation. Therefore, unaffected, optimally active mitochondria are indispensable in a healthy and vital body. A mutation in the DNA of the semi-autonomous mitochondria (mtDNA) may cause an inheritable insufficiency that is due to decreased energy generation needed for adequate development. Sperm mitochondria will not enter the egg cell during fusion of male and female gametocytes. Since women with mutated mtDNA will increasingly know and realize the effect of such mutation in their own body, they will more often ask for treatment to stop the effect of such inconvenient mutation in their progeny. Thus far, solutions for this problem were thought to be: (i) nucleus transplantation just after fertilization into a nucleus-free egg cell of a second healthy woman and later (ii) transplantation of healthy mitochondria from a second woman into the egg cell before fertilization. Although both transplantations create babies with three, instead of two-parents that have contributed to the genetic content, in case of the newer mitochondria transplantation technique the part of the second woman is somewhat more reduced, but still clearly present. Thus, assisted-reproduction techniques that mix egg cell mitochondria from two women may create not only 'three-parents' babies, but also fears for 'three-parents' babies, since this handling may create non-scientific problems, especially regarding emotional, ethical, religious and juridical aspects of life. Transplantation of healthy sperm mitochondria of the partner into the egg cell with insufficient mitochondria is thought to be the best solution for this problem, since it may create a 'two-parents' instead of a 'three-parents' baby. This only implies that at the moment of (successful) transplantation the biological dogma is broken that mitochondria are maternally inherited: the mitochondria of the maternal line of the woman will have been substituted by the mitochondria of the maternal line of the man.

Female↗

The management of unexplained infertility.

UNLABELLED: Unexplained infertility is a diagnosis made by exclusion after all of the standard investigations have revealed no abnormality (1). The range of the prevalence is from 6 to 60 percent (23), depending on the diagnostic criteria. This article reviews the literature in the management of unexplained infertility; published data suggest no benefit of danazol or bromocriptine. The empirical use of clomiphene citrate suggests that ovarian stimulation using clomiphene citrate can double the spontaneous pregnancy rate (52, 58, 59). Induction of ovulation with human menopausal gonadotrophin (hMG) yields an overall pregnancy rate between 2 and 26 percent per cycle (68, 74). These results seem to be lower than those reported for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) procedures in similar patients (25-30 percent (92, 95)). Based on the literature, a rational treatment plan for treating infertility in couples with unexplained infertility includes up to four cycles of clomiphene citrate with or without intrauterine insemination (IUI). Superovulation with hMG and IUI or stimulated intrauterine insemination (SIUI) is the next step for three-cycle treatments and if unsuccessful, one of the variants of assisted reproductive techniques (ART) should be considered. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will understand the appropriate tests and work up for unexplained infertility, the various treatment options for the unexplained infertility couple including which drugs are effective and not effective, and to be able to outline an appropriate treatment plan for such patients.

Diagnostic Techniques, Obstetrical and Gynecologic↗

Assisted reproductive medicine: current Islamic bioethical rules.

The advances and wide availability of assisted reproductive techniques represent the dramatic changes that have occurred in infertility treatment and in attitudes towards the different options faced by both physicians and patients. It is a human right that individuals can freely choose reproductive options. Though reproductive choice is basically a personal decision, yet it is not totally so. Islam is a comprehensive system that regulates the spiritual as well as civil aspects of individual and communal life. It aims to develop the unique personality of the individual and a distinct culture for the community based on Islamic ideals and values. The basic concept of Islam is to avoid mixing genes as Islam enjoins the purity of genes and heredity.

Attitude to Health↗

Assisted reproduction in the treatment of polycystic ovarian syndrome.

Treatment of patients with polycystic ovary syndrome (PCOS) with assisted reproductive techniques is a great challenge for the infertility specialist. Patients with PCOS demonstrate many problems, such as excessive body weight and hyperinsulinaemia, that render management more complex. Prior to treatment with IVF, the PCOS patient should be thoroughly evaluated for disclosure of endometrial neoplasia, hyperinsulinaemia, and other general health related problems. Ovarian stimulation for IVF carries the risks of overstimulation and severe hyperstimulation, which should be avoidable in most cases with preventive measures. The outcome in terms of pregnancy and implantation rates is similar for patients with PCOS when compared with patients undergoing IVF for other indications. There are some questions regarding oocyte and embryo quality in women with PCOS. This manifests itself in lower fertilization rate and decreased embryo quality in some studies. However, increased numbers of oocytes available for insemination or ICSI compensate for decreased fertilization rates and embryo quality. More recent studies suggest higher cumulative conception rates in women with PCOS when compared with controls. In-vitro maturation (IVM) of oocytes retrieved from non-stimulated or minimally stimulated cycles represents a viable option that should be considered seriously when assisted conception is attempted. Results of IVM, however, should be improved further and generalized before the technique can be advocated as the initial treatment approach in these patients.

Cellular Senescence↗

[Signs of discovery. (Re-)construction of infertility in the age of reproduction medicine].

Even though infertility seems to be an old phenomenon, it will be argued that it was discovered in a new way once it became necessary to legitimize the technological possibilities of artificial fertilization at the end of the 1970s. With the birth of the first test-tube baby in 1978 the public became excited about the new possibilities of medical procreation. Reactions were extremely divided because extracorporeal fertilization seemed to undo the difference between natural organisms and technologically created human beings. Today reproductive medicine is an accepted field of gynecology and an increasing number of couples make use of it (even in managing their fertility). This development was the result of the successful integration of reproductive techniques into the discourse of infertility which is by no means self-evident. From the perspective of how societies communicate about reproduction it becomes clear that the dividing line between fertility and infertility is disappearing.

Adult↗

Avoiding multiple pregnancies in ART: multiple pregnancies: a test case for the moral quality of medically assisted reproduction.

Although most professional societies have issued guidelines to diminish the number of embryos to be transferred during assisted reproduction techniques, the incidence of multiple pregnancies remains unacceptably high. The negative psychological, social and medical consequences for the patients and their offspring easily outweigh the benefits in terms of increased success rates. Multiple pregnancies would never be tolerated if the 'best interest of the child' standard was applied as strictly to these consequences, as it is to controversial family forms. The persistence of high multiple pregnancy rates is largely due to the pressure brought to bear on the physicians to increase the overall success rate. The fertility specialist should inform the patients about the risks and benefits of a multiple transfer but ultimately the specialist should decide how many embryos to transfer. Multifetal reduction is an ethically acceptable solution if, and only if, the physician has taken all reasonable steps to prevent the occurrence of a multiple pregnancy. Finally, an additional strategy to decrease the incidence of multiple pregnancies is proposed, i.e. to extend the professional responsibility of the fertility specialist to all steps of procreation including pregnancy, birth and neonatal care.

Child↗

[Human clone or a delayed twin?].

Cloning is a natural mode of asexual reproduction for many organisms, which results in nearly identical copies of cells or organisms. In animals, including humans, identical twins are an example of natural cloning. In the case of sheep, scientists succeeded to produce the "delayed" identical twin. Dolly, of a mature animal by a rather complex and inefficient procedure. However, if this procedure is perfected, it will be useful to clone beloved pets and important laboratory animals. It will be much less suited for making (cloning) "delayed twin" of mature persons because of high costs together with present experimental uncertainties. The only required regulation for human cloning is that somebody must be legally, including financially, responsible for the results of such novel reproductive technique.

Animals↗

[Legal and ethical problems in assisted reproduction--case report].

OBJECTIVE: The objective of the study is to evaluate legal and ethical aspects of the assisted reproduction in the Czech Republic. These aspects are described in the context of the concrete case. DESIGN: Case report. SETTING: Department of Social Medicine, Medical and Health Care Administration Faculty of the Masaryk University, Brno and Centre of the Reproductive Medicine Zlín. SUBJECT AND METHOD: The description of the concrete case that happened in the Czech Republic. A widow asked for the artificial insemination using the sperm of her deceased husband. CONCLUSION: It was concluded that there is absolutely insufficient legal regulation of the assisted reproduction techniques, it does not respond to the development of the medical knowledge and it responds insufficiently to the ethical dilemmas concerning the assisted reproduction.

Bioethical Issues↗

Permeation properties of three-dimensional self-affine reconstructions of porous materials

A binary medium generation method is presented, which is capable of producing three-dimensional reconstructions of porous solids. The method is based on the midpoint displacement and successive random addition technique, which is, essentially, a graphical reproduction technique for the generation of self-affine media that follow fractional Brownian motion (FBM) statistics. Thresholding of the site values at the desired porosity value leads to three-dimensional porous constructions, the correlation degree of which is defined by the preselected value of the Hurst exponent. The correlation length of such single-cell media is comparable to the size of the working cell and, therefore, this approach would be of local use only. To remedy this problem, a method for producing multicell FBM media is presented, which is capable of generating media with size considerably larger than the correlation length and, as such, they can be employed to simulate a variety of actual porous solids. The percolation properties of these reconstructions are investigated and the specific surface area is calculated as a function of the porosity, the number of interwoven cells, and the Hurst exponent value. Furthermore, the flow equations are solved numerically within the void space of the three-dimensional FBM media and the effects of structure porosity and correlation degree on the permeability are studied. Application of the methodology to a sandstone sample as a case study showed a very good agreement of the numerical predictions for the permeability with actual permeability measurements and with the permeability estimate using a serial sectioning technique.

Journal Article↗

Interaural cross-correlation coefficients in stereo-reproduced sound fields.

Interaural cross-correlation coefficients (ICCCs) were measured in stereo-reproduced fields where a KEMAR (Knowles electric manikin for acoustic research) was located. These ICCCs were then compared with those in an ideal, diffuse sound field. The ICCCs in a reverberant field are not reproduced accurately using a conventional two-channel stereo-reproduction technique. In four-channel stereo reproduction, however, the ICCCs can, for the most part, be reproduced accurately as in an ideal, diffuse sound field. Some experimental results are also shown for binaural discrimination of the ICCCs.

Acoustics↗

Transcervical tubal transfer of gametes and embryos.

The benefit of intrafallopian transfer techniques is still disputable in assisted reproductive techniques. On this background, alternatives to laparoscopic transfer procedures are in development. Current transcervical intrafallopian transfers of gametes and embryos are lacking success and reproducibility of results. New developments in catheter techniques and optical systems are offering new concepts for more successful transcervical approaches and preparing the basis for truly prospective studies.

Embryo Transfer↗

Current concepts and novel applications of LH activity in ovarian stimulation.

Luteinizing hormone (LH) is a crucial physiological regulator of the human menstrual cycle. LH activity is also contained in many medications used to treat anovulation and to stimulate multiple folliculogenesis for assisted reproduction techniques. However, LH activity had previously been regarded as just a contaminant of follicle-stimulating hormone (FSH)-containing products and deemed potentially detrimental for reproductive function. Novel experimental and clinical evidence now suggests that the administration of pharmacological amounts of LH activity, instead of being harmful, is therapeutically advantageous, particularly in the support and modulation of ovarian folliculogenesis. The aim of this article is to provide an overview of the effects of LH activity administration in ovarian stimulation and to outline novel unconventional gonadotropin regimens that might improve the efficacy, safety and convenience of ovulation induction.

Anovulation↗

Reproduction decision making for couples affected by HIV: a review of the literature.

Medical issues faced by HIV-affected couples include transmission risks between partners and between mother and child, as well as the technologies and procedures available to reduce those risks. Assisted reproductive techniques discussed are artificial insemination, in vitro fertilization, intracytoplasmic sperm injection, self-insemination, and timed intercourse. It is important that physicians be aware of reproductive options available to couples affected by HIV and be prepared to engage in nonjudgmental dialogue with patients. This review is the result of a literature search performed to identify useful information to counsel HIV-serodiscordant and HIV-seroconcordant couples facing decisions on reproduction.

Adult↗

Improved techniques for first-trimester fetal reduction using simultaneous abdominal and transvaginal ultrasonographic guidance. Preliminary report.

Simultaneous transabdominal injection of potassium chloride (KCl) assisted by transvaginal ultrasonographic guidance was evaluated in 5 patients who conceived due to various assisted reproductive techniques and ovarian stimulation. All 5 underwent first-trimester fetal reduction for multiplicity of high-order pregnancies. Four sets of triplets were reduced to twin, and 1 twin pregnancy was reduced to a singleton. Less than 2 ml of 2 mEq/ml KCl per fetus was needed for each case. No fetal or maternal complications nor technical failure attributable to the procedure were recorded. All pregnancies were delivered > or = 35 weeks of gestation. Transabdominal fetal reduction using simultaneous transvaginal ultrasonographic guidance for selective feticide combines the benefits of both the transabdominal and transvaginal approaches, mainly in selected cases in which some experts prefer the abdominal route, but find it technically difficult to practice. Further experience is needed to confirm our encouraging preliminary results before drawing any definitive conclusions.

Abdomen↗

Assisted reproduction: a Jewish perspective.

Judaism values medicine as a noble profession. Physicians are mandated by the Bible to heal, and those who are ill are obligated to seek healing from their physicians. In Jewish thought, infertility is considered an illness. Hence, in spite of many Jewish legal and ethical questions, assisted reproductive techniques such as artificial insemination, in vitro fertilization and surrogate motherhood, within certain limited circumstances, are viewed with favor by most current rabbinic authorities, provided the couple is unable to have a child in the normal manner and after standard medical or surgical interventions have failed.

Ethics, Medical↗

Islamic tradition and medically assisted reproduction.

Sunni Islam has no supreme legal authority and disagreement by doctors of Islamic law over all issues not clarified by Islamic law is physiological. This is the case with Medically Assisted Reproduction: after an initially critical attitude, tolerance, limited exclusively to homologous practices, is spreading, whilst recourse to heterologous practices is considered on a par with adultery or fornication and is therefore prohibited. 'Unnatural' reproduction techniques are not generally deemed capable of violating divine will.

Female↗

Factors affecting commercial application of embryo technologies in dairy cattle in Europe--a modelling approach.

Reproductive techniques have a major impact on the structure of breeding programmes, the rate of genetic gain and dissemination of genetic gain in populations. This manuscript reviews the impact of reproductive technologies on the underlying components of genetic gain and inbreeding with special reference to the role of female reproductive technology. Evaluation of alternative breeding schemes should be based on genetic gain while constraining inbreeding. Optimum breeding schemes can be characterised by: decreased importance of sib information; increased accuracy at the expense of intensity; and a factorial mating strategy. If large-scale embryo cloning becomes feasible, this will have a small impact on the rate of genetic gain but will have a large impact on the structure of breeding programmes.

Animals↗