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This paper explores the role of assisted reproductive technology in the management of infertility from an Israeli viewpoint. The author discusses the effects of the generous provision of IVF facilities in Israel when compared with other countries and explains the apparent conflict between the service and research functions of these practices.
Ultrasound imaging in reproductive sciences offers new opportunities regarding optimization of the induction of the sexual cycle and ovulation, superovulation regimes, contraception programs, semen collection and testicular sperm extraction techniques, ovum pick up and ovarian transplantation procedures, as well as the application of artificial insemination, embryo collection and transfer. In non-domestic species, most of which lack basic data, ultrasonography is an ideal tool to study reproductive biology in both captive and wild populations. The use of this imaging modality led us to develop new, or modify established, reproductive technologies. Ultrasonography has been an integral part of over 200 assisted reproduction procedures in 17 mammalian species performed by our research team between 1992 and 1999. These procedures included the initial characterization of sexual cycles, hormonal cycle induction, semen collection by electroejaculation or manual stimulation, non-surgical artificial insemination (AI), non-surgical embryo transfer and temporary hormonal contraception. For these investigations, a variety of newly developed equipment was applied and species-specific hormonal treatments designed. We used several commercial and customized ultrasound systems with a variety of technical features. Some relevant improvements of these applications will be described and the role of ultrasonography elucidated to.
BACKGROUND: One in six Australian couples of reproductive age experience difficulties in conceiving a child. Once a couple has been appropriately assessed, assisted reproductive technology (ART) techniques can be used to overcome problems with ovulation, tubal patency, male fertility or unexplained infertility. OBJECTIVE: This article discusses the range of ART techniques available to subfertile couples. DISCUSSION: Intracytoplasmic sperm injection is now the most common form of ART used in Australia, being used in almost half of all fresh cycles, with in vitro fertilisation being used in approximately one-third of all fresh cycles.
Ethics is an essential dimension of newer reproductive technologies. In this rapidly evolving field, there is a need for an ethical framework to guide both clinical practice and research. In this article, we provide such a framework that incorporates ethical principles, professional virtues, and the concept of the fetus as a patient. We then apply this framework to an important current clinical issue: the number of embryos to be transferred during in vitro fertilization; in addition to an emerging research issue: gene transfer research on in vitro embryos.
OBJECTIVE: To review and analyze records on heterotopic pregnancy occurring after ovulation induction and assisted reproductive technologies. DATA IDENTIFICATION: Case reports in the English literature related to the topic were identified through a computerized bibliography search up to December 1993. CONCLUSIONS: The incidence of heterotopic pregnancies increased in recent years because of the escalating use of new reproductive technologies in infertile patients and has stabilized at approximately 1:100 pregnancies with these procedures. The main reasons for development of such a condition in these patients are past tubal or pelvic disease and multiple ovulations or multiple ET. Progress has been made in diagnosis of heterotopic pregnancy during the last two decades, mainly because of development of ultrasonographic techniques, especially transvaginal ultrasonography. Treatment of heterotopic pregnancy should be prompt to avoid maternal morbidity and mortality from extensive intraperitoneal bleeding. No increased intrauterine fetal mortality due to hemoperitoneum has been proven in the present review, except in advanced cornual pregnancies. More experience is needed for application of new treatment modalities such as salpingocentesis, which are used successfully for ectopic pregnancy, in treatment of heterotopic pregnancy. With early diagnosis and skillful treatment, the outcome of the intrauterine pregnancy is favorable and its survival rate should increase in the future.
In assisted reproductive technology (ART), serum levels of several key hormones are used to evaluate ovarian follicular reserve and to monitor gonadotropin-stimulated follicle growth. Currently, serum estradiol, FSH, LH and inhibin B levels are examined and combined at the beginning of the menstrual cycle to evaluate the functional status of the ovaries, providing information for appropriate ovarian stimulation treatment and prognosis for in vitro fertilization (IVF) outcome. In women undergoing in vitro fertilization and embryo transfer (IVF-ET), ovulation stimulation is monitored by serial measurements of estradiol, progesterone and LH to monitor follicular growth, evaluate the progression of stimulation, adjust daily gonadotropin therapy for each patient, and predict the optimal day for the induction of ovulation. We analyze the importance of each hormone and discuss the discrepancies frequently reported resulting from differences in methods.
CONTEXT: During the past two decades, assisted reproductive technologies (ARTs) have revolutionised the treatment of infertility. ARTs now account for between 1% and 3% of annual births in many western countries and in-vitro fertilisation (IVF) services are growing worldwide. In general, the incidence of abnormalities at birth is reassuringly low and children develop normally. Nevertheless, it is important to monitor the safety of ARTs as clinical protocols evolve and new technologies emerge. STARTING POINT: Three recent studies all report an unexpectedly high incidence of Beckwith-Wiedemann syndrome (BWS) in children conceived with ARTs. Six of 149 cases were reported from a British BWS registry (J Med Genet 2003; 40: 62-64); the same numbers were recorded in a French registry (Am J Hum Genet 2003; 72: 1338-41), and a further seven children have been reported in the USA (Am J Hum Genet 2003; 72: 156-60). These frequencies are extraordinarily high for such a rare congenital condition and such findings are reminiscent of reports of sporadic cases of the imprinting disorder, Angelman syndrome, which has also been linked with ARTs. WHERE NEXT? Continuing surveillance of children conceived with ARTs is needed, including monitoring birth defects, development, and cancer. Studies will need to be prospective and multicentre, and should include molecular characterisation of epigenetic abnormalities, including the methylation status of imprinting control regions within imprinted gene clusters.
BACKGROUND: In women treated by assisted reproductive technology (ART), early pregnancy loss (EPL) reduces the initial success. Risk factors for EPL, however, have not been comprehensively studied. This study assesses some potential risk factors in ART pregnancies. METHODS: Altogether 1196 pregnancies, defined as serum hCG >or=10 IU/l on day 16 +/- 1 after oocyte retrieval, were included in this study. EPL was defined as pregnancy loss that occurred before 6-7 weeks gestation. Risk factors investigated were maternal age, body mass index (BMI), smoking and polycystic ovary syndrome (PCOS) status, infertility aetiology, response to stimulation, quality and number of embryos replaced and treatment type. RESULTS: Overall EPL was 16%. The risk of EPL was not linearly related to either age or BMI. Though women >40 years old had an increased risk, this was not significant after adjusting for other factors. The risk in both lean (BMI <18.5 kg/m(2)) and very obese (BMI >35 kg/m(2)) women was also not significantly higher in multivariate analysis. There was no effect of PCOS. Smoking or transfer of 'poor quality' embryo(s) was associated with a significant increased risk of EPL after adjusting for other factors. CONCLUSION: Smoking and transferring poor quality embryos increased EPL, while the effects of age, obesity and other risk factors were not significant in a multivariate analysis.
Thirty-seven patients who underwent assisted reproductive technology programme, in vitro fertilisation or embryo transfer and gamete intra-fallopian transfer, were randomised into two groups in order to evaluate frequency of premature spontaneous LH surge when stimulated with different type of hMG. An hMG (FSH:LH = 1:1) was administered for eighteen patients (group A) and the different highly purified hMG (FSH:LH = 19:1) was administered for nineteen patients (group B). Blood samples are drawn from day 3 of the cycle until hCG administration, and serum LH level are measured in the frozen samples. There were no statistical difference in the total amount of hMG used before hCG injection, days of hMG injection and the number of oocytes retrieved between two groups. The premature spontaneous LH surge occurred only one patient in group A (5.6%), but more frequent LH surge was observed in group B (42.1%) (p < 0.05). It is suggested that the different FSH/LH ratio may be the reason for the difference of the incidence of premature spontaneous LH surge.
In this paper I will discuss three areas in which advances in human reproductive technology could occur, their uses and abuses, and their effects on society. First is the potential to drastically increase the success rate and availability of in vitro fertilization and embryo freezing. Second is the ability to perform biopsies on embryos prior to the onset of pregnancy. Finally, I will consider the adding or altering of genes in embryos, commonly referred to as "genetic engineering". As new reproductive technologies pass from experimental models into the potential for medical utilization, I believe that it will be important for lawmakers everywhere to avoid the impulse to outlaw procedures that a society believes to be 'unnatural' at a first glance. Rather, I would hope that they can respond thoughtfully with legislation that serves two purposes--to protect the rights of couples to overcome infertility or to reduce the risk of genetic disease in their children-to-be, and more importantly, to protect children-to-be from the abuses that could result from some of the practices that I will discuss.
BACKGROUND: Numerous studies have evocated the clinical usefulness of serum AMH levels as a predictor of ovarian response and pregnancy in assisted reproductive technology cycles. Nevertheless, the analysis of the literature shows a great dispersion in serum AMH concentrations obtained with different methods from almost comparable populations. METHODS: We compared two commercial immunoassays (AMH Beckman Coulter ELISA and AMH DSL ELISA) and we evaluated the AMH levels in serum as a prognosis value for ovarian response and pregnancy in assisted reproductive technology cycles. RESULTS: We found a close linear relationship between the two methods but AMH levels were almost 4.6-fold lower with the DSL kit than with the Beckman Coulter kit. We found a significant and positive correlation between the number of mature ovocytes inseminated and AMH levels obtained with the two methods. Whatever the ELISA used, we found no significant difference between AMH level of pregnancy and non pregnancy groups. Indeed, using the Beckman Coulter method, all pregnant patients had serum AMH levels over 1.4 microg/L. Conversely, no cut-off value can be found for the DSL kit. CONCLUSION: Our results show clearly for the first time that AMH results are method dependent even if the correlation obtained between the two methods remained excellent. The Beckman Coulter AMH ELISA should produce clinical agreement when used for prognosis purposes on patients undergoing assisted reproduction.
OBJECTIVE: To determine what percentage of embryos achieved through assisted reproductive technology (ART) do not result in a live birth and to examine the relationships among the number of embryos transferred, infants delivered, and embryos wasted. DESIGN: Retrospective correlational study of the U.S. summary data of ART results for the years of 1995-2001. PATIENTS: Fertility clinics reporting data to the Society of Assisted Reproductive Technology (SART). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistics for ART cycles using fresh, nondonor eggs and embryos were derived, and the percentage of embryos wasted each year was calculated. Trends over time were evaluated for percent embryos wasted, the average number of embryos transferred, and the delivery per transfer rate. Correlations between these variables were analyzed. RESULT(S): The percentage of embryos transferred that did not produce a live birth was 90.8 in 1995 and decreased to 84.9 in 2001. This trend significantly correlated with a reduction in the number of embryos transferred (from 3.9 to 3.1) and with an improvement in delivery rate per transfer (25% to 33.4%). CONCLUSION(S): The vast majority of embryos produced in vitro and transferred fail to develop into an infant, supporting the concept that only a small fraction of embryos has the capacity to become a live birth. Clinicians should strive to reduce embryonic wastage without an adverse effect on delivery rates by perfecting methods of ovarian stimulation and embryo screening, and by transferring fewer embryos.
OBJECTIVE: To systematically evaluate the available literature regarding the relationship between assisted reproductive technology and ovarian cancer. DATA SOURCES: Computerized search of 6 databases from 1966 (or closest) to present: Cochrane Controlled Trials Register, Cancerlit, CINHAL, Current Contents, PubMed in process (formerly called PreMEDLINE), and MEDLINE. We collected references from the bibliographies of reviews, original research articles, content experts, and conference proceedings to find published and unpublished literature. METHODS OF STUDY SELECTION: Case-control and cohort studies are included. The population of interest is treated infertile women, the control population is untreated infertile women, and the intervention or exposure of interest includes the following fertility medications: clomiphene citrate, gonadotropins, human chorionic gonadotropin, and gonadotropin releasing hormone agonists. The primary outcome is incident, primary ovarian cancer. Three cohort and 7 case-control studies were included in the quantitative analyses. TABULATION, INTEGRATION, AND RESULTS: The Newcastle-Ottawa Quality Assessment Scales were used. Two investigators independently extracted study methods, sources of bias, and outcomes. The following information was recorded: publication information, subject characteristics, intervention information and outcomes. Studies combined were sufficiently homogeneous for quantitative summary. Case-control and cohort data showed a significantly elevated risk for exposure of infertility medications and ovarian cancer in subjects who underwent assisted reproductive technology compared with general population controls (1.52; 95% confidence interval [CI] 1.18 to 1.97). When cases of ovarian cancer were compared with infertile controls for exposure to infertility medications, the odds ratio (0.99; 95% CI 0.67, 1.45) was not elevated. However, cohort data comparing outcome in treated infertile patients with untreated infertile patients suggests that treated patients may tend to a lower incidence of ovarian cancer-odds ratio = 0.67 (95% CI 0.32, 1.41). CONCLUSION: Ovarian cancer does not appear to be increased in treated infertile patients versus untreated infertile patients. Treated infertile patients may have a lower incidence of ovarian cancer than untreated infertile patients.
This is a prospective study to assess the psychiatric morbidity in Chinese infertile women who underwent treatments with assisted reproductive technology and also the impact of treatment failure. The 30-item General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were employed before and 3 weeks after the assisted reproductive technology treatment. Data from 372 patients who completed the questionnaires and failed the treatment were analyzed. Before treatment, 33% of the participants scored above the GHQ cutoff, and 8% had a BDI score of 20 or above, signifying moderate to severe depression. Following failed treatment, 43% scored above GHQ cutoff, and 8% had BDI scores 20 or above. The posttreatment GHQ and BDI scores were significantly higher than the corresponding scores at baseline (p < 0.001). About 13% of the participants reported self-harm ideas. The severity of depression following a failed treatment was positively associated with the duration of infertility (p < 0.05), but not with the posttreatment BDI scores, age, education, and number of previous treatment episodes. Our results show that one third of the women who sought infertility treatment had an impaired psychological well-being. Following failed treatment, there was a further deterioration in mental health, and about 10% of the participants were moderately to severely depressed. Proper psychological care and counseling should be an integral part of infertility management among the Chinese population.
Potential rates of genetic progress are limited by biological constraints, which along with genetic parameters determine the structure of breeding programs to be employed for maximum genetic improvement. The objective here is to determine whether current progeny-testing programs in dairy cattle, which have been dictated and constrained by low female reproductive rates, need to be changed to capitalize on new reproductive technologies and how these changes should be implemented. Many differences between breeding programs diminish when selection on animal model genetic evaluations across all age and population groups is adopted as a strategy. Progeny-testing schemes then evolve toward dispersed open nucleus breeding schemes when multiple ovulation and embryo transfer is used on bull-dams. Nucleus breeding schemes have been advocated to capitalize on embryo transfer technology. In nucleus breeding schemes utilizing high reproductive rates, inbreeding, rather than reproductive rate, poses a limit to genetic progress, and strategies that maximize response to selection while limiting inbreeding need to be employed. One strategy is mating each dam to several sires rather than only one sire. In vitro embryo production techniques can be used to facilitate such mating strategies. Large-scale in vitro embryo production programs, in which large numbers of embryos per female are tested in the commercial population, offer the greatest potential for genetic gain with low rates of inbreeding. Cloning has an impact mainly on methods for dissemination of genetic improvement. Breeding herds, genetically inferior to marketed clones, are needed for continuous genetic gain. Reproductive technologies offer the potential for genetic improvement. Whether new breeding programs require changes in population structure, e.g., by creation of nucleus breeding herds, depends mainly on logistics and on quantity and quality of field information.
It is estimated that one couple in six in the United States has to deal with issues of infertility. It is assumed that worldwide rates are comparable. In 35% of cases, the infertility is caused by female reproductive problems, in 35% by male reproductive problems, in 15% by multiple factors and in 15% the cause is unknown. Medical and scientific advances in Assisted Reproductive Technology (ART) have created 12 different pregnancy producing options for infertile couples. An ART infant could have as many as five parents (i.e. a donor father, a donor mother, a surrogate or gestational mother, and the couple actually rearing the child). These technical, medical, and moral complexities have resulted in a nightmare of accompanying legal complexities: anonymous donors versus those with identification disclosed, parental rights, grandparental rights, the rights of siblings and of the extended families; sperm, ovum and embryo "ownership", custody, visitation and inheritance rights and multiple other issues challenge a system of laws that evolves far slower than the technological realities to which it applies. This presentation will describe Assisted Reproductive Technology advances and the legal implications inherent in them. Case histories will be discussed.
PURPOSE: The purpose of this study was to evaluate the influences of tropical weather on patients with different ovarian responses in the treatment of assisted reproductive technology. METHODS: Six-hundred fourty-seven women underwent their first treatment cycles were retrospectively analyzed. Patients received embryo transfer either 3 days or 5 days after oocyte retrieval, depending on the number and quality of embryos on day-2. RESULTS: Significant correlations were demonstrated in the top quality embryo rates of day-3 and day-5 embryo transfers with temperature, humidity, and atmosphere pressure. The cumulative light hours negatively correlated with the implantation and pregnancy rates of day-3 embryo transfer (-.282 and -.282, respectively), while they positively correlated with those of day-5 embryo transfer (.225 and .224, respectively). CONCLUSIONS: These results clearly suggest that weather may exert influences on the outcome of assisted reproductive technology. Patients with different ovarian responses or blastocyst culture and transfer may modify weather influences.
OBJECTIVES: To link data from the US assisted reproductive technology (ART) registry with the Massachusetts birth-infant death file to create a comprehensive dataset on the circumstances surrounding conception and maternal and infant outcomes for a population of ART-conceived infants. METHODS: The authors sought to link data for 3704 ART-conceived live-born infants from 2703 deliveries in 1997-1998 involving Massachusetts resident mothers who gave birth in Massachusetts, Rhode Island, New Hampshire, or Connecticut to their corresponding Massachusetts birth record using a two-stage algorithm. Maternal and infant dates of birth served as the primary linkage variables. Maternal names for a subset of the ART-conceived infants were obtained and used in the second stage of the algorithm to confirm a sample of records that matched in Stage I, to resolve duplicate matches, and to link unmatched records. RESULTS: In Stage I, 78% of ART deliveries matched with only one Massachusetts record, 2% matched with two records, and 20% remained unmatched. Overall, the complete algorithm using maternal name data for a portion of records yielded an 89% linkage rate. Nearly all of the records that matched during Stage I that were evaluated with maternal name data in Stage II were confirmed as correctly linked. CONCLUSIONS: This project confirms that high-yield data linkage can be achieved in the absence of specific identifiers (e.g., name and social security number). Nonetheless, additional matches were achieved when name data were obtained. This linkage creates the first population-based file in the US capturing detailed information on ART births.