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The interpretation and use of statistics in assisted reproductive technologies.

This article has discussed some of the uses and limitations of currently available statistics for ART programs. A well-known example from statistics states that flipping a coin will produce "heads" 50% of the time and "tails" 50% of the time, provided that the coin is flipped enough times. Experience also shows that the result of individual flips cannot be predicted. Similarly, in ART, statistics can only give general probabilities and not meaningful predictions of the outcome of any particular cycle. Patients should be aware of the limits of statistical analysis as it applies to their individual treatment.

Adult↗

Questioning the assumptions in the debate on assisted reproduction: comment on the House of Commons report Human Reproductive Technologies and the Law.

The House of Commons Science and Technology Committee has issued a series of non-dogmatic recommendations. Also regarding elective sex selection, it has adopted a controversial position. Sex selection should be allowed for family balancing. However, the acceptability of preimplantation genetic diagnosis as a method for selecting the embryos can be questioned on the basis of social harm. In countries with a shortage of medical personnel and a limited health care budget, elective procedures are a loss to society. This loss should be compensated by imposing a 'social compensation tax' for every application of elective sexing.

Advisory Committees↗

Indication of varicocelectomy in the era of assisted reproductive technology: prediction of treatment outcome by noninvasive diagnostic methods.

Of 103 patients who underwent varicocelectomies, 87 underwent all the diagnostic methods: color Doppler ultrasonography (DOP), scrotal deep body temperature (DBT), and scrotal scintigraphy (SSG). Total motile sperm (TM) was calculated. The positivities of DOP, DBT, and SSG were 67, 51, and 90%, respectively. In the patients <30 years old, TM increased in the DBT-positive group. In older patients, positive for DBT indicated poor improvement of TM, whereas positive for DOP indicated better response in the group. Patients older than 30 years and positive for DBT, but not DOP, should be counseled directly to receive intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection.

Body Temperature↗

A successful assisted reproductive technology satellite program.

A satellite program was implemented to provide IVF to interested infertile couples living in a five-state area. Thirty-six gynecologists were established as satellite sites after appropriate screening and training. No attempt was made to interchange reference serum specimens between laboratories. Patients were seen at Mayo Clinic for an initial consultation and did not return until the ovulatory dose of hCG was administered. There was no difference in cancellation, clinical pregnancy, and delivery rates between satellite and central unit monitored patients. Satellite monitoring decreases patient inconvenience and time away from home and the workplace without compromising cycle outcome.

Delivery of Health Care↗

Gonadotropin-releasing hormone antagonists: impact of IVF practice and potential non-assisted reproductive technology applications.

PURPOSE OF REVIEW: To provide the clinician with updated knowledge of the most recent findings on the clinical use of gonadotropin-releasing hormone antagonists. RECENT FINDINGS: Gonadotropin-releasing hormone antagonists, which have recently been introduced in clinical practice, cause an immediate suppression of gonadotropin secretion by competitive blocking of pituitary gonadotropin-releasing hormone receptors. Thus, they are effective in preventing the premature luteinizing hormone surges during ovarian stimulation for in-vitro fertilization and may improve the patient's response to lower doses of gonadotropins. Better patient acceptance, shorter treatment cycles and fewer follicles and oocytes are also reported. Data existing so far concerning the necessity of luteal phase support after the use of gonadotropin-releasing hormone antagonists show that it might not be mandatory when used in clomiphene citrate costimulated cycles or in intrauterine insemination cycles. The use of gonadotropin-releasing hormone antagonists seems to be safe for pregnant women and their offspring. All sex-hormone-dependent disorders, currently treated with gonadotropin-releasing hormone agonists, may in future be indications for a gonadotropin-releasing hormone antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. The vast majority of the available clinical data up till now, however, are in assisted reproduction and prostate cancer. SUMMARY: It is expected that the availability of gonadotropin-releasing hormone antagonist will lead to the use of 'softer' ovarian stimulation protocols, which will be shorter, cheaper and safer compared with the conventional protocols.

Female↗

Screening standards in assisted reproductive technologies. Is the British Andrology Society recommendation to recruit cytomegalovirus negative semen donors only, a reasonable one?

The British Andrology Society recently recommended the exclusion of all cytomegalovirus (CMV) seropositive semen donors to prevent the risk of congenital CMV infection. The recommendation is based on the results of recent studies that identified a high percentage of symptomatic congenital CMV infections in newborns of women with CMV seropositivity pre-existing to pregnancy and on the fact that CMV can be detected in semen of CMV seropositive men. These are not new data. CMV seropositive women can infect their fetuses with their own latent CMV strain that can reactivate, or with an exogenous strain that can be transmitted to them by a sexual partner, but also by contacts, for example with an excreting child. The efficiency of these various ways of transmission to the fetus and the factors that could influence this transmission are for the moment completely unknown. An infectious virus is recovered by culture in the semen of <5% of CMV seropositive men. Exclusion of a large population of donors on the sole criteria of a positive CMV serology introduces the general message that this part of the male population is also not suitable as possible partners in couples who have no fertility problems. The problem of congenital infection in neonates of CMV seropositive women is a complex one that has just begun to be investigated. No data exists concerning this risk in the setting of assisted reproduction. We think that alternatives to the drastic BAS recommendation exist and should be more deeply discussed.

Cytomegalovirus Infections↗

Lesbian and bisexual women's recommendations for improving the provision of assisted reproductive technology services.

Qualitative focus groups were conducted with lesbian and bisexual women who were themselves or whose partners were in the process of trying to conceive (n = 6); who were biological parents of young children (n = 7); and who were nonbiological parents of young children or whose partners were currently pregnant (n = 10) to explore their donor insemination service needs and to provide recommendations for improved or additional services. The 10 recommendations generated by participants included providing cues that the service is lesbian and bisexual positive; offering lesbian- and bisexual-specific infertility support; providing opportunities for women to make informed choices about use of interventions consistent with their known or presumed fertility; and offering accessible services to known sperm donors, including gay men.

Attitude to Health↗

1995 assisted reproductive technology success rates: national summary and fertility clinic report.

Although ART offers important options for the treatment of infertility, the decision to use ART involves many factors in addition to success rates. Going through repeated ART cycles requires substantial commitments of time, effort, money, and emotional energy. Couples and individuals considering ART should carefully examine all related financial, psychologic, ethical, and medical issues before beginning treatment. They should also contact ART clinics to discuss their specific medical situation and potential for success using ART. The next published report will feature 1996 data and provide a listing of clinics that did not submit data. Eventually, the annual report will include information from all U.S. fertility clinics, not just those that are SART members.

Adult↗

Ethical issues and controversies in assisted reproductive technologies.

The current ethical issues and controversies concerning in vitro fertilization revolve around micromanipulation of the gametes, cryopreservation of the fertilized ova, selective termination in multiple pregnancies, surrogacy, and gamete donation. At the basis of these ethical issues is the philosophic question of personhood, or the term "human person," and the consideration given to the normal weight that is ascribed to the various forms of living matter that are found in the process of development after human spermatozoa have been placed together with harvested oocytes in the petri dish. The papers of very special importance and special importance written during the past year on these ethical problems are listed and classified. The summaries of their arguments and positions on these problems are enumerated.

Abortion, Induced↗

[Health of children born after the infertility treatment with Assisted Reproduction Technology].

Since the birth of Louise Brown in July 1978 and the birth of the first intracytoplasmic sperm injection (ICSI) child in January 1992 many couples with female-factor or male-factor infertility can be helped to overcome their infertility resulting in a delivery and birth of a child. Over a million children have been born from assisted conception worldwide. Newer techniques being introduced appear less and less 'natural', such as intracytoplasmic sperm injection (ICSI), but there is little information on these children beyond the neonatal period. This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos transferred, and embryo availability. ART is associated with low increase risk of congenital malformations, major birth defects and genetic and imprinting disorders.

Child↗

Application of intracytoplasmic sperm injection in assisted reproductive technologies.

Intracytoplasmic sperm injection (ICSI) entails the mechanical insertion of a chosen spermatozoon directly into the cytoplasm of an oocyte. Due to the consistent fertilization and pregnancy outcome, ICSI is routinely used to treat azoospermic patients where spermatozoa are retrieved by epididymal aspiration or testicular biopsy. Since male subfertility has been associated with a higher incidence of genomic defects, ranging from numerical chromosomal abnormalities to Yq microdeletions, concerns have been raised as to the risk of transmitting genetic defects to the offspring. Screening for such defects can provide invaluable information for appropriate counselling prior to ICSI treatment. In order to address these concerns, a follow-up of the children born after ICSI treatment was conducted.

Adult↗

Artificial reproductive technology achievements for optimizing embryo quality.

Evaluation of morphological characteristics, to date, has been the most widely accepted method for the selection of embryos with higher developmental ability and optimization of the outcome of in vitro fertilization (IVF). Improvement in clinical results has also been pursued through attempts to generate embryos of high quality or to identify more reliable selection criteria. This work evaluates the possibility of improving embryo quality and subsequent IVF outcome in situations in which creation of supernumerary embryos is not allowed. Optimization of gamete selection and conditions of insemination, such as hormonal therapy to improve sperm quality of patients undergoing intracytoplasmic sperm injection treatment, use of power Doppler image for follicle selection, short coincubation of gametes during insemination, and use of a polscope for spindle detection, is described.

Blastocyst↗

The role of the laboratory in the handling of epididymal sperm for assisted reproductive technologies.

This report describes the historical experience of our laboratory in the handling and processing of epididymal sperm from men with congenital absence of the vas deferens. Three different methods of sperm preparation were used: swim-up or resuspension in the first group of patients treated, mini-Percoll in the second group, and mini-Percoll used in conjunction with pentoxifylline and 2' deoxyadenosine in the third group. Twenty-four percent of cases achieved fertilization in group I, whereas in groups II and III the rate was 59% and 57%, respectively. Fertilization rates in each group were 6.5% in group I, 16% in group II, and 35% in group III. Three pregnancies were obtained in group I, 13 in group II, and 2 in group III. Groups II (21%) and III (63%) were able to have excess embryos to cryopreserve.

Epididymis↗

New approaches to assisted reproductive technologies.

Egg infertility remains the greatest challenge in the treatment of the infertile couple. As women increasingly delay attempts at childbearing, egg infertility has become more prevalent. Attempts to overcome egg infertility by superovulation and in vitro fertilization have produced an epidemic of multiple gestations, itself a major public health concern. The pathophysiology of egg infertility arises from chromosomal nondisjunction. Cytogenetic analyses of polar bodies and/or blastomeres currently provide the most powerful predictors of egg infertility. Approaches that label all chromosomes (spectral karyotyping and comparative genomic hybridization), or identify predisposition to aneuploidy (spindle imaging, telomere length measurement) are on the horizon. For the foreseeable future, the treatment of egg infertility will be limited to egg donation for severe cases and transfer of the most viable embryos for milder cases. Oocyte reconstitution not only lacks evidence of clinical efficacy, but also biological credibility, given that growing evidence supports the primacy of chromosomes themselves in meiotic nondisjunction.

Aneuploidy↗

The andrology laboratory in an Assisted Reproductive Technologies program. Quality assurance and laboratory methodology.

Assuring the highest possible quality of care to the patient is the first goal of the andrology laboratory. Quality control and quality assurance as they apply to the andrology laboratory are outlined, and special problems in quality control for sperm function assays are addressed. An example of the patient review process is presented. Quality of care also depends on the ability of the laboratory to perform appropriate tests of sperm function that can diagnose sperm defects, predict success or failure of in vitro fertilization, and lead to rational therapies for sperm dysfunctions. Methods for, and diagnostic value of, sperm swim-out, enhanced sperm penetration assays, acrosome reaction assessment, motility analysis of capacitating sperm, and sperm-zona binding assays are reviewed. No single test, other than in vitro fertilization itself, is capable of providing a complete diagnosis or a highly accurate prediction. A battery of sperm function tests, arranged in an algorithm, is presented as a theoretically better approach.

Diagnostic Tests, Routine↗

New reproductive technologies.

The ethical calculus is described. There are four entities that have a stake in all ethical decisions. These are the individual, family, community and society at large. Values assigned to these entities can be modified by experience, cultural background, religious authority and the law. In the simple case of in vitro fertilization (IVF), there seems to be general international acceptance, except for the official position of the Roman Catholic Church, the origin of which dissent is extensively discussed. There is concern about the number of pre-zygotes/pre-embryos to be transferred, the disposition of any unfertilized egg and the reporting of results. Clear ethical considerations arise as IVF is applied in more complex situations, such as unmarried couples, the use of donor gametes and donor pre-embryos, the use of cryopreservation, intracytoplasmic sperm injection (ICSI), prenatal genetic diagnosis, surrogate gestational motherhood and research on the pre-embryo. The ethical, religious and legal acceptance of these depends on the weight given to elements of the ethical calculus as described in the chapter.

Ethics, Medical↗

Evaluation of a cut-off value for sperm motility after different hours of incubation to select the suitable reproductive technology (IVF or ICSI).

BACKGROUND: The aim of this study was to enhance the predictability of conventional semen parameters for in-vitro fertilization outcome. The utility of late sperm motility in presence of a cumulus-oocyte complex after different hours of incubation was investigated to predict the outcome of IVF in borderline and normal ejaculates (at least 5 x 10(6) motile sperm). METHODS: The study was done on 52 infertile couples undergoing conventional in-vitro fertilization and embryo transfer. Sperm were prepared by the Percoll cushion centrifugation with swim-down. Cocultures were established by inseminating the cumulus-oocyte complexes with 100000 motile spermatozoa and incubating them for 48 hours. Another 100000 spermatozoa were incubated in culture medium for 48 hours. Sperm motility (WHO a+b) was determined at 0, 4, 24 and 48 hours of incubation. RESULTS: The fertilization rate was 65.5% (42.9-88.1). The conventional semen parameters did not correlate with the fertilization rate. Sperm motility measured after different hours of incubation was found to be significantly positively correlated with the fertilizing ability of sperm in vitro in Spearman's rank correlation test: motility after 0 h (p<0.02), after 4 h (p=0.0025). after 24 h (n.s.) and after 48 h (p=0.0071). Cut-off values for late sperm motility were determined and differences in fertilization rates were calculated for these cut-off values after different hours of incubation. A cut-off value of 20% progressive motile spermatozoa after 48 hours gave the best statistical power (fertilization rate 71.7 vs. 50.2%, p<0.001). Significant differences in the fertilization rates were also observed for a cut-off value of 35% after 24 hours of incubation (70.1 vs. 46.2%, p=0.001) and for a cut-off point of 60% after 4 hours (72.4 vs. 51.5%, p=0.001). CONCLUSIONS: The predictive power of sperm motility after 48 h for fertilization outcome provides support in the decision-making process within the assisted reproduction setting. If less than 20% of sperm are motile after 48 h micromanipulatory techniques should be considered.

Adult↗

Risk during pregnancy and birth after assisted reproductive technologies: an integral view of the problem.

Pregnancy and obstetric outcome are the final steps in infertility treatment. Additional data from recent studies demonstrate an increased risk for pregnancy course and obstetric outcome. These risks include an increased risk for intrauterine growth retardation, preeclampsia, and premature birth. Children born after in vitro fertilization and intracytoplasmic sperm injection (ICSI) have an increased risk for major malformations compared with spontaneously conceived pregnancies. Patients have to be counseled about these risks. The question is where these increased risks originate. At present, there are insufficient data available from pregnancies established following hormonal treatment or intrauterine insemination cycles. Therefore, the question is still open for debate, whether either in vitro culture or infertility per se or perhaps other components of the treatment cycle contribute to this risk. There is some evidence that at least the ICSI technique or the in vitro culture technique is not the only or most prominent factor. A long time to pregnancy with subsequent spontaneous pregnancy results in a similar risk profile as pregnancies following infertility treatment. This article discusses a possible pathogenetic model for these observations.

Female↗