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Fetal subjects and maternal objects: reproductive technology and the new fetal/maternal relation.

This essay examines three tendencies nurtured in the practices of reproductive technology - tendencies with profoundly disturbing implications for us as individuals and as social beings. They are: 1) the increasing subjectification of the fetus (that is, the increasing tendency to posit a fetal subject), 2) the increasing objectification of the gestating woman, leading to her representation as interchangeable object rather than unique subject, and 3) the increasing tendency to conceive of the fetus and the mother as social, medical, and legal antagonists. Considering the construction of fetus, mother, and the fetal/maternal relation in earlier (Western) historical periods, a contemporary work of literature, a government report, and the popular press, I argue that as the fetus is increasingly being understood as a subject, the mother is increasingly being reduced to an antagonist, an obstacle to fetal health, and an object. The essay concludes by offering some tentative conclusions about the general process of fetal subjectification in the United States and Europe.

Advisory Committees↗

Assisted reproductive technology: both sides now.

Over the last 2 decades, increased pregnancy success has been achieved by assisted reproductive technology (ART) at the expense of perinatal well-being from a corresponding rise in multiple births. Multiple pregnancies increase the risk of prematurity, low birth weight, and perinatal morbidity and mortality. Together with recent concerns about possible birth defects and long-term developmental sequelae, modern ART practice is increasingly scrutinized for such adverse perinatal outcomes. Hence, it is mandatory for infertility specialists to look at ART from both sides now--its success and its complications. This article summarizes the prevalence of multiple pregnancies, the risk of low birth weight and possible birth defects, and long-term developmental sequelae associated with ART and discusses some potential approaches to minimizing these perinatal complications. Reducing the number of embryos transferred is an immediate action that can minimize adverse perinatal outcomes associated with multiple births. Continuous refinements in ART techniques will allow the transfer of a single embryo with equivalent rates of pregnancy success leading to a healthy, singleton live birth.

Chromosome Aberrations↗

Epigenetics and assisted reproductive technology: a call for investigation.

A surprising set of recent observations suggests a link between assisted reproductive technology (ART) and epigenetic errors--that is, errors involving information other than DNA sequence that is heritable during cell division. An apparent association with ART was found in registries of children with Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma. Here, we review the epidemiology and molecular biology behind these studies and those of relevant model systems, and we highlight the need for investigation of two major questions: (1) large-scale case-control studies of ART outcomes, including long-term assessment of the incidence of birth defects and cancer, and (2) investigation of the relationship between epigenetic errors in both offspring and parents, the specific methods of ART used, and the underlying infertility diagnoses. In addition, the components of proprietary commercial media used in ART procedures must be fully and publicly disclosed, so that factors such as methionine content can be assessed, given the relationship in animal studies between methionine exposure and epigenetic changes.

Angelman Syndrome↗

Gametes and embryo epigenetic reprogramming affect developmental outcome: implication for assisted reproductive technologies.

There is concern about the health of children who are conceived with the use assisted reproductive technologies (ART). In addition to reports of low birth weight and chromosomal anomalies, there is evidence that ART may be associated with increased epigenetic disorders in the infants who are conceived using these procedures. Epigenetic reprogramming is critical during gametogenesis and at preimplantation stage and involves DNA methylation, imprinting, RNA silencing, covalent modifications of histones, and remodeling by other chromatin-associated complexes. Epigenetic regulation is involved in early embryo development, fetal growth, and birth weight. Disturbances in epigenetic reprogramming may lead to developmental problems and early mortality. Recent reports suggest the increased incidence of imprinting disorders such as Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma in children who are conceived with the use of ART. These may result from an accumulation of epigenetic alterations during embryo culture and/or by altered embryonic developmental timing. Further research is urgently needed to determine whether a causal relationship between ART and epigenetic disorders exists. Until then, cautious review of both short-term and long-term ART outcomes at a national level is recommended.

Embryo, Mammalian↗

Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States.

OBJECTIVE: To examine perinatal outcome among singleton infants conceived with assisted reproductive technology (ART) in the United States. METHODS: Subjects were 62,551 infants born after ART treatments performed in 1996-2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), preterm delivery, preterm LBW, and term LBW were examined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated. RESULTS: The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ethnicity, singleton infants born after ART in 2000 had elevated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnancies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagnosis of tubal factor, conception using in vitro fertilization without intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days. CONCLUSION: Singletons born after ART remain at increased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas preterm LBW was stable. LEVEL OF EVIDENCE: III

Adult↗

The predictive value of a single beta human chorionic gonadotropin in pregnancies achieved by assisted reproductive technology.

OBJECTIVE: To investigate whether a single serum beta-hCG in pregnancies achieved by assisted reproductive technologies (ART) can accurately predict pregnancy viability and, in viable pregnancies, multiple gestation. DESIGN: Four hundred sixty-one consecutive successful ART pregnancies were studied retrospectively. Seventy-one of the 461 patients were excluded because their beta-hCG was either drawn on the incorrect day or outside our facility. Three hundred ninety subjects had a serum beta-hCG drawn 14 days after ET or 16 days after gamete transfer. The beta-hCG samples were analyzed by immunoradiometric assay based on the Third International Reference Standard (IRS) (First International Reference Preparation (IRP)). Pregnancy status was followed, at minimum, through the first trimester. RESULTS: One hundred fifty (38%) of the 390 were found to be nonviable, resulting in spontaneous abortion (n = 38, 10%), ectopic pregnancy (n = 27, 6%), or biochemical pregnancies (n = 85, 22%). A statistically significant difference by the Scheffe F-test was found between the mean beta-hCG value of the nonviable (115 mIU/mL) (conversion factor to SI unit, 1.00) and viable (428 mIU/mL) pregnancies. The positive predictive value of a single beta-hCG > 100 mIU/mL in distinguishing viable from nonviable pregnancies was 0.83 (sensitivity 91%, specificity 71%). Of the 240 viable pregnancies, 74 (32%) were multiple gestations (57 twins, 14 triplets, and 3 quadruplets). The mean beta-hCG of the singleton pregnancies (266 mIU/mL) was significantly different from that of the multiple gestations (792 mIU/mL). The positive predictive value of a single serum beta-hCG < or = 400 mIU/mL in distinguishing singleton from multiple gestations was 0.92 (sensitivity 86%, specificity 82%). CONCLUSION: A single early serum beta-hCG may be used in ART pregnancies to predict which pregnancies will continue beyond the first trimester and to identify multiple gestations. Early reassuring tests may reduce anxiety.

Adult↗

Use of the antral follicle count to predict the outcome of assisted reproductive technologies.

OBJECTIVE: To evaluate the predictive value of the antral follicle count in patients undergoing assisted reproductive technologies (ARTs). DESIGN: Prospective study. SETTING: Tertiary care institutional hospital. PATIENT(S): Consecutively seen patients undergoing ARTs such as IVF-ET, gamete intrafallopian transfer, and tubal embryo transfer (TET). INTERVENTION(S): The ovarian antral follicle number was determined by transvaginal ultrasonography on the first or second menstrual day, before the administration of gonadotropins, in patients undergoing ARTs. MAIN OUTCOME MEASURE(S): Ovulation induction was accomplished with the use of GnRH agonist down-regulation combined with FSH and menotropin stimulation. Gamete intrafallopian transfer or TET was performed in patients with patent fallopian tubes, and IVF-ET was undertaken in the remaining patients. Analysis of variance and Mantel-Haenszel monotonic test for trends were used for data analysis. RESULT(S): A total of 149 treatment cycles for 130 couples were performed during the study period. The procedures performed included 89 ETs, 26 gamete intrafallopian transfers, 13 TET cycles, and 21 incomplete cycles (9 poor responders, 6 failed retrievals, and 6 nonfertilization cycles). All treatment cycles were divided into three groups according to the number of antral follicles (i.e., < or = 3, 4-10, and > or = 11) to evaluate the influence of various factors. The antral follicle count correlated significantly with patient age, day 3 serum FSH level, use of gonadotropins, serum estradiol concentration, number of oocytes retrieved, and, later, number of oocytes or embryos transferred. The group of patients who had a lower antral follicle count also had a significantly higher rate of cycle cancellation compared with the other two groups (68.8% vs. 5.3% and 0, respectively). No pregnancies occurred in the low antral follicle count group, whereas there was a trend toward an increasing number of pregnancies per attempt as the number of antral follicles increased (0, 23.7%, and 36.8%, respectively). CONCLUSION(S): It is easy to determine the number of antral follicles with a diameter of 2-5 mm on the first or second day of menstruation, or just before the administration of exogenous gonadotropins. We were able to predict the ovarian response and pregnancy results of patients undergoing ARTs with the use of this simple procedure.

Embryo Transfer↗

Graduated Embryo Score and soluble human leukocyte antigen-G expression improve assisted reproductive technology outcomes and suggest a basis for elective single-embryo transfer.

OBJECTIVE: To evaluate assisted reproductive technology (ART) outcomes by using Graduated Embryo Score (GES) and soluble human leukocyte antigen-G (sHLA-G) expression to select embryos for transfer on day 3. DESIGN: Prospective cohort. SETTING: Private practice. PATIENT(S): Women undergoing fresh ART cycles (n = 209). INTERVENTION(S): In vitro fertilization using standard protocols. Embryos scoring GES of > or =70 using were selected for transfer on the basis of sHLA-G expression in the culture media on day 2. MAIN OUTCOME MEASURE(S): Pregnancy, implantation, and multiple-gestation rates. RESULT(S): Ongoing gestations increased with the number of embryos expressing sHLA-G (37%, 42%, 58%, and 56% with 0, 1, 2, or 3 sHLA-G(+), respectively). With at least two sHLA-G(+) embryos, ongoing gestation and implantation rates were higher than those with fewer than two sHLA-G(+). Differences were even higher for women aged < or =37 years. With at least two sHLA-G(+) embryos, the odds ratio (95% confidence interval) was 1.59 (1.51-1.68) for ongoing gestation compared with the case of fewer than two sHLA-G(+). Age was the most important predictor of outcome; the odds ratio (95% confidence interval) was 2.07 (1.98-2.16) for ongoing gestation in women aged < or =37 years with at least two sHLA-G(+) embryos, compared with the case of women aged 38-40 years. CONCLUSION(S): Day 3 embryo transfer using GES and sHLA-G improves ART outcomes by increasing predictive accuracy. High twin rates suggest that couples with at least two sHLA-G(+) embryos consider elective single-embryo transfer.

Adult↗

A satellite system for assisted reproductive technologies: an evaluation.

The University of North Carolina at Chapel Hill (UNC) Satellite System for Assisted Reproductive Technologies (ART) was initiated in 1984, and now serves most of North Carolina and parts of two adjoining states. The system was established to enhance the care of infertile couples at the community level, to assure a sufficiently large volume of patients at UNC Hospitals to support appropriate quality control measures, and to allow couples undergoing ART to have most of their care in their own community. This paper reports an assessment of the outcome of this program. Neither pregnancy rates, nor any other measurable result of the program differed between patients managed in the satellites and those cared for at UNC Hospitals.

Delivery of Health Care↗

Stress in assisted reproductive technology: implications for nursing practice.

In a follow-up study about women's experience of assisted reproductive technology (ART) some events were identified as particularly stressful, including making the decision to try ART, starting treatment, waiting for results after a scan, having oocyte collection, the 2 week wait after embryo transfer and finding out that the treatment was unsuccessful. On the basis of these findings, a review of the literature and extensive clinical practice as a nurse co-ordinator in an ART programme, implications for nursing practice are discussed and strategies to use that may help reduce stress and improve the well-being of ART participants are suggested.

Embryo Transfer↗

Safety issues in assisted reproductive technology: aetiology of health problems in singleton ART babies.

The frequency of health problems in singleton assisted reproductive technologies (ART) babies is higher than in singletons from spontaneous gestations. Any of the following factors may be involved: in-vitro technology, ovarian stimulatory drugs and infertility itself. A literature review on premature birth, low birth weight, perinatal mortality and major birth defects in children conceived from infertility treatments was conducted. Only publications comparing the outcome of pregnancy in an infertile group of patients to a matched control group were selected. The analysis of the outcome of singleton pregnancies resulting from IVF versus artificial insemination, obtained with or without the use of ovarian stimulatory agents and obtained with or without the use of a semen donor, suggests that female infertility is an important risk factor. Criteria for screening at-risk infertile women have not yet been identified. Prospective studies designed to identify precisely the aetiology of health problems in singletons ART babies will have to be conducted. The absence of criteria correlating at-risk infertile women to health problems in their children does not allow a gynaecologist the opportunity to offer infertility treatments to the least susceptible patients.

Congenital Abnormalities↗

Morphologic and histopathologic characteristics of placentas from twin pregnancies spontaneously conceived and from reduced and nonreduced assisted reproductive technologies.

OBJECTIVE: To prospectively evaluate morphologic and histopathologic characteristics of placentas from twin pregnancies obtained by assisted reproductive technologies (ART) and non-ART and to evaluate the influence of previous fetal reduction on placental features. STUDY DESIGN: Fifty-five placentas from consecutive deliveries of ART-obtained and 50 placentas from consecutive deliveries of non-ART-conceived twin pregnancies were investigated by one pathologist, who was blinded to specimen origins. The patients' demographic and clinical data were also recorded. RESULTS: The mean maternal and gestational ages were similar in both groups. ART-obtained pregnancies were associated with an increased incidence of pregnancy complications and lower mean birth weight. Placentas from ART-obtained pregnancies were mostly of the dichorionic type and were thinner, weighed less and had more infarctions as compared to non-ART-conceived pregnancies. Placental characteristics of reduced ART-obtained twin pregnancies were comparable to those of nonreduced ones. The second twin's placenta in all groups weighed less and had a higher incidence of anomalous umbilical cord insertion. CONCLUSION: Placentas from ART-obtained twin pregnancies appear to have more pathologic features as compared to those of non-ART-conceived ones. Fetal reduction does not significantly affect the remaining placentas.

Case-Control Studies↗

Infertility practice management. I. Leadership and management style: results from the 2002 survey of 374 Society for Assisted Reproductive Technology member centers.

OBJECTIVES: To identify current trends in management and leadership styles in Society for Assisted Reproductive Technology (SART) member infertility centers; and to understand the similarities and disparities that exist in physicians', administrators', and staff perceptions of management and leadership styles in these centers. MATERIALS AND METHODS: Questionnaires were developed to collect information on the leadership and management styles in place in SART member infertility centers. Survey instruments were distributed to the 374 SART centers. Survey instruments for one physician, the center administrator, and six staff members (two each in nursing, laboratory, and administration) were issued to the SART liaison in each of the SART member centers. Respondents included physicians, practice administrators, nurses, technicians, patient services, billing, and support staff. RESULTS AND DISCUSSION: Analysis of respondents' answers revealed that surveyed staff members reported a fairly high degree of job satisfaction. Physician and administrator management styles seemed to fall between interactive and directive styles; however, physicians and administrators perceived themselves as being more interactive than other staff members viewed them. Overall, extreme differences were unlikely, given the reported high degree of job satisfaction. Finally, survey outcome data were compared with responding centers' ART outcome rates as published by the Centers for Disease Control and Prevention (CDC). CONCLUSIONS: Overall, although employee job satisfaction seemed to be high, there were statistical differences between groups for several questions; the disparities in responses for these questions are indicators for potential management and leadership consideration. In addition, statistical correlations were found between the responses for several questions and the centers' respective CDC-published ART outcome rates.

Adult↗

Results in the United States with sperm microaspiration retrieval techniques and assisted reproductive technologies. The Sperm Microaspiration Retrieval Techniques Study Group.

Improved methods of urological microsurgery and of various assisted reproductive technologies have resulted in the ability to achieve pregnancies with sperm aspirated microsurgically from men with bilateral congenital absence of the vasa deferentia or with ductal obstructions that cannot be surgically reconstructed. A survey was conducted of the results of such procedures performed in the United States during approximately 2 years. Female partner ovarian stimulation was initiated in 219 instances at 22 centers. Of the 219 procedures 23 (11%) were terminated without attempting any form of gamete fertilization or insemination of the wife for various reasons (no sperm or too few sperm retrieved, poor to absent sperm motility or poor quality eggs). The etiology of azoospermia in the 219 procedures was congenital absence of the vasa deferentia in 115 cases (52%), other congenital conditions in 15 (7%), failed vasectomy reversal in 37 (17%), infection in 4 (2%), other conditions (mainly ejaculatory dysfunctions that did not respond to electroejaculation and complex ductal obstructions) in 26 (12%) and not specified in 22 (10%). When only patient sperm was used pregnancy was achieved in 12 of 115 wives (10%) of those men who had congenital absence of the vasa deferentia and in 0 to 14% of the wives of men whose azoospermia was caused by other conditions. Of the 219 menstrual cycles in which ovarian stimulation was initiated pregnancy occurred in 24 (11%) with patient sperm and in 9 (4%) with donor sperm. Of these 33 pregnancies a full-term, live delivery occurred in 17 (52%), while 8 (24%) were ongoing at the time of reporting, 2 (6%) miscarried, 3 (9%) were chemical pregnancies, 1 (3%) resulted in a stillborn child and the outcome was unknown in 2 (6%). This new therapy offers only a modest chance of pregnancy. However, it affords men with azoospermia the opportunity to achieve paternity with their own sperm when other therapies are not available or applicable.

Epididymis↗

Advanced reproductive technologies in South American camelids.

The authors chose to discuss only a small portion of the potential advanced reproductive technologic procedures that hold promise in fertility management of llamas. The future of this area is very bright; one's lack of imagination, simple prejudice, or careless planning are the only factors that will limit progress. As these techniques are accepted, they should be used carefully and judiciously to maximize reproductive potential, and not simply to maximize profits by unscrupulous individuals.

Animals↗

Comparisons of pregnancy loss patterns after intracytoplasmic sperm injection and other assisted reproductive technologies.

OBJECTIVE: To compare outcome of pregnancies after intracytoplasmic sperm injection (ICSI) with those of other assisted reproductive technologies. DESIGN: Pregnancy outcomes after ICSI were followed prospectively and compared with pregnancy outcomes after IVF with fresh and frozen ETs and donor oocyte cycles. SETTING: A private tertiary referral center for genetics and infertility in Fairfax, Virginia. PATIENTS: One hundred thirty-six couples achieving pregnancy after undergoing ICSI, 71 after IVF, 35 donor oocyte recipients, and 19 after transfer of frozen-thawed embryos. INTERVENTIONS: In vitro fertilization and/or ET for all couples. Dilatation and curettage to obtain products of conception for chromosome analysis in 28 women experiencing spontaneous abortion. MAIN OUTCOME MEASURES: Pregnancy outcomes were classified as preclinical loss, clinical loss, and ongoing pregnancy. RESULTS: The mean frequency of preclinical pregnancy loss was 26% after ICSI, 28% after IVF, 3% after ET using donor oocytes, and 11% after frozen ET. The rate of clinical loss after ICSI (21%) was compared with IVF (18%), donor oocyte cycles (11%), and frozen ETs (21%). CONCLUSIONS: Intracytoplasmic sperm injection is not associated with an increase in pregnancy losses, clinical or preclinical, compared with conventional IVF.

Abortion, Spontaneous↗

Antioxidant potential of human serum albumin: role in the recovery of high quality human spermatozoa for assisted reproductive technology.

Human serum albumin (HSA) is being considered as an alternate media for sperm enrichment in assisted reproductive technology (ART) because of recent concern with the use of Percoll. In this study, we compared HSA and Percoll for 1) sperm recovery, 2) reactive oxygen species scavenging potential, and 3) effects on total oxidative stress to spermatozoa. The spermatozoa-enriched fractions obtained from Percoll (80%:40%) and HSA (12%) were monitored for sperm motility, viability, hypoosmotic swelling test (HOST), and adenosine triphosphate (ATP) levels. The effect of superoxide anions (O2.-) on donor human spermatozoa was observed in the presence of either HSA or Percoll media. A combination of luminol and the Cypridina luciferin analog 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyraz in-3-one hydrochloride was used as a highly sensitive chemiluminescence probe in our hypoxanthine and xanthine oxidase-based assay for O2.-. Sperm membrane total oxidative stress was determined by measuring levels of the prostanoid 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha). Significant differences in sperm parameters between the Percoll-enriched spermatozoa (motility 60%+/-4%, viability 56%+/-6%, and HOST 73%+/-7%) and those enriched with HSA (motility 84%+/-5%, viability 85%+/-4%, and HOST 84%+/-3%; P < 0.01) were observed. Adenosine triphosphate levels were significantly higher, by almost 50%, in samples processed with HSA than with Percoll (P=0.03). The dismutation rate of O2.- in HSA (slope -6.8) was significantly lower than in Percoll (slope -87.0; P < 0.01). Sperm motility and ATP levels decreased at a slower rate after treatment with O2.- in the presence of HSA when compared to Percoll; moreover, spermatozoa in HSA regained partial motility after 2 hours, whereas spermatozoa in Percoll were immobilized. No significant differences in 8-iso-PGF2alpha levels in spermatozoa enriched by either HSA or Percoll were observed. We conclude that the HSA sperm enrichment procedure improves the recovery of higher quality spermatozoa compared to Percoll and, because of its antioxidant properties, may be useful in processing high leukospermia semen samples for ART purposes.

Adenosine Triphosphate↗