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Assisted reproduction technology, multiple births, and adverse perinatal outcome.

The increase in the rate of multiple pregnancies in Australia in recent years is primarily due to the use of assisted reproduction technology. Compared to singleton births, fetal, neonatal, and perinatal mortality rates are 3-6 times higher in twins and 5-15 times higher in multiple births of a higher order. Cerebral palsy rates among survivors are six times higher in twins and twenty times higher in triplets. The increased risks in multiple pregnancies are not entirely explained by their higher prematurity and low birthweight rates. In Australia, the practice of transferring more than three embryos in any one assisted reproduction technology cycle has declined in recent years and, as a result, the number of multiple pregnancies from assisted reproduction technology has also declined. Nevertheless, assisted reproduction technology pregnancies remain to have poorer than normal outcome with regards to spontaneous abortion, ectopic pregnancy, preterm birth, low birthweight, and perinatal mortality. Infants born after assisted reproduction technology have a higher neonatal morbidity rate, including a greater requirement for assisted ventilation, and a higher long-term neurodevelopmental disability rate. These adverse outcomes following assisted reproduction technology are partly due to the increased risk of multiple pregnancy and partly due to preterm and low birthweight. This fact and the lack of evidence that the transfer of more than two embryos improves pregnancy rates, make it advisable to limit the number of embryos transferred to no more than one or two per cycle.

Australia↗

[Newborns from assisted reproductive technology at the Hospital de São João].

Over the last 20 years, assisted reproductive technology has been increasingly used. Ever since the first newborn resulting from artificial insemination, over two centuries ago, thousands more children were born resulting from these techniques. In Portugal, assisted reproductive technology began in 1985 at the Hospital de São João (HSJ). Although the success of these techniques is often judge by the pregnancy rate, occasionally by the birth rate, the most important issue of this evaluation should be the neonatal health. A retrospective study to evaluate the use of assisted reproductive technology at the HSJ, as well as the occurrence of complications during pregnancy and the evolution of the newborns in the neonatal period, during the period between 1999 and 2003, was undertaken. A hundred and thirty-eight pregnant women were included, which stands for about 1% of the total number of pregnant women at the HSJ in the period in question, with an average of age 32.2 +/- 4.1 and of infertility 6.2 +/- 3.8 years. The number of attempts for a successful pregnancy was 2.7 +/- 2.1. The most used technique was intracytoplasmatic sperm injection. Eighteen percent of the pregnancies resulted in abortion. The incidence of multiple pregnancies was 30%. A hundred and fifty-six infants were born, which stands for about 1% of the total number of births at the HSJ in the period in question, with a gestational age of 36.4 +/- 3 weeks and weight at birth of 2674.5 +/- 761.4 g. The incidence of preterm birth was 41%. Seventy-eight percent of the newborns had a good neonatal outcome, whereas the other 22% were admitted to a neonatal intensive care unit for an average period of 17 days. The most frequent neonatal morbidity was respiratory. One newborn died. Despite the need for several attempts of assisted reproductive technology, pregnancy complications, neonatal morbidity and mortality, the use of these techniques allowed for most couples to overcome their infertility problem.

Adult↗

Unmanaged care: the need to regulate new reproductive technologies in the United States.

In the aftermath of allegations of the misuse of human eggs in the United States, questions are being raised about whether profitable reproductive services should continue to function in a free market under the aegis of physicians or should be regulated. Other countries in which reproductive technologies are employed to a significant degree have developed regulations governing their use, many as a result of recommendations made by inter-disciplinary commissions that solicited public input. Policy makers in the United States have been reluctant to regulate reproductive technologies, however, because their use is politically controversial, they want to whittle down government, some do not consider infertility an illness, and some believe regulation would interfere with the right to reproduce. Yet the unfettered use of reproductive technologies can create such harms as lack of informed consent, providing procedures not medically indicated for financial gain, practice by unqualified personnel, injury to patients and donors, failure to screen donated gametes, and inadequate medical record keeping. Americans place special value on the welfare of children and those who bring them into the world. Such values can outweigh individual procreative liberty when new reproductive technologies are at issue. Although the optimal course would be to establish a regulatory body to govern reproductive technologies, this is not politically feasible now. The newly established National Bioethics Advisory Commission provides a forum in which issues surrounding reproductive technologies should be addressed at this time in the United States.

Advisory Committees↗

Assisted reproductive technology surveillance--United States, 2001.

PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). REPORTING PERIOD: 2001. DESCRIPTION OF SYSTEM: CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, and RESOLVE: The National Infertility Association. RESULTS: In 2001, a total of 29,344 live-birth deliveries and 40,687 infants resulting from 107,587 ART procedures were reported from 384 medical centers in the United States and U.S. territories. Nationally, 80,864 (75%) of ART treatments used freshly fertilized embryos from the patient's eggs; 14,705 (14%) used thawed embryos from the patient's eggs; 8,592 (8%) used freshly fertilized embryos from donor eggs; and 3,426 (3%) used thawed embryos from donor eggs. Overall, 40% of ART procedures that progressed to the transfer stage resulted in a pregnancy; 33% resulted in a live-birth delivery (delivery of > or =1 infant); and 21% resulted in a singleton live birth. The highest live-birth rates were observed among ART procedures using freshly fertilized embryos from donor eggs (47%). The greatest numbers of ART procedures were performed among residents of California (13,124), New York (12,379), Massachusetts (8,151), Illinois (7,933), and New Jersey (6,011). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. The ratio of number of ART procedures per million population ranged from 74 in Idaho to 1,273 in Massachusetts, with a national average of 371 ART procedures started per million persons. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in live birth rates by patient (e.g., women aged < or =40 years) and treatment characteristics (e.g., ovulatory dysfunction, endometriosis, or unexplained infertility) was observed. The risk for a multiple-birth delivery was highest for women who underwent ART transfer procedures using freshly fertilized embryos from either donor eggs (42%) or from their own eggs (36%). Among ART transfer procedures in which the patient's own eggs were used, an inverse relation existed between multiple-birth risk and patient age. Number of embryos transferred and embryo availability (an indicator of embryo quality) were also strong predictors of multiple-birth risk. Of the 40,687 infants born, 46% were twins, and 8% were triplet and higher order multiples. The total multiple-infant birth rate was 53%. Approximately 1% of U.S. infants born in 2001 were conceived through ART. Those infants accounted for 16% of multiple births nationally. INTERPRETATION: Whether an ART procedure resulted in a pregnancy and live-birth delivery varied according to different patient and treatment factors. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos transferred, and embryo availability (an indicator of embryo quality). PUBLIC HEALTH ACTION: ART-related multiple births represent a sizable proportion of all multiple births nationally and in selected states. Efforts should be made to limit the number of embryos transferred for patients undergoing ART.

Adult↗

Assisted reproductive technology surveillance--United States, 2000.

PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). REPORTING PERIOD COVERED: 2000. DESCRIPTION OF SYSTEM: CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, and RESOLVE: The National Infertility Association. RESULTS: In 2000, a total of 25,228 live-birth deliveries and 35,025 infants resulting from 99,629 ART procedures were reported to CDC from 383 medical centers that performed ART in the United States and U.S. territories. Nationally, 75,516 (76%) of ART treatments were freshly fertilized embryos using the patient's eggs; 13,312 (13%) were thawed embryos using the patient's eggs; 7,919 (8%) were freshly fertilized embryos from donor eggs; and 2,882 (3%) were thawed embryos from donor eggs. The national live-birth delivery per transfer rate was 30.8%. The five states that reported the highest number of ART procedures were California (13,194), New York (11,239), Massachusetts (8,041), Illinois (7,323), and New Jersey (5,506). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. Overall, 47% of women undergoing ART-transfer procedures using freshly fertilized embryos from their own eggs were aged <35 years; 23% were aged 35-37 years; 19% were aged 38-40 years; 7% were aged 41-42 years; and 4% were aged >42 years. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in patient age, infertility diagnoses, history of past infertility treatment, and past births was observed. Nationally, live-birth rates were highest for women aged <35 years (38%). The risk for a multiple-birth delivery was highest for women who underwent ART-transfer procedures using freshly fertilized embryos from either donor eggs (40%) or from their own eggs (35%). Among women who underwent ART-transfer procedures using freshly fertilized embryos from their own eggs, further variation by patient age and number of embryos transferred was observed. Of the 35,025 infants born, 44% were twins, and 9% were triplet and higher order multiples, for a total multiple-infant birth rate of 53%. Patient's residing in states with the highest number of live-birth deliveries also reported the highest number of infants born in multiple-birth deliveries. INTERPRETATION: Whether an ART procedure was successful (defined as resulting in a pregnancy and live-birth delivery) varied according to different patient and treatment factors. Patient factors included the age of the woman undergoing ART, whether she had previously given birth, whether she had previously undergone ART, and the infertility diagnosis of both the female and male partners. Treatment factors included whether eggs were from the patient or a woman serving as an egg donor, whether the embryos were freshly fertilized or previously frozen and thawed, how long the embryos were kept in culture, how many embryos were transferred, and whether various specialized treatment procedures were used in conjunction with ART. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, and the number of embryos transferred. In addition, the increased risk for multiple births has a notable population impact in certain states. PUBLIC HEALTH ACTIONS: As use of ART and ART success rates continue to increase, ART-related multiple births are an increasingly important public health problem nationally and in many states. The proportion of infants born through ART in 2000 that were multiple births (53%) was substantially higher than in the general U.S. population during the same period. Data in this report indicate a need to reduce multiple births associated with ART. Efforts should be made to limit the number of embryos transferred for patients undergoing ART. In addition, continued research and surveillance is key to understanding the effect of ART on maternal and child health.

Adult↗

Imprinting disorders after assisted reproductive technologies.

PURPOSE OF REVIEW: To assess the evidence of an increased risk of imprinting diseases in children born after use of assisted reproductive technologies. RECENT FINDINGS: Imprinting disorders occur when the epigenetic programming during gametogenesis is disturbed, or when this programming is not sufficiently sustained during the process of fertilization and early embryonic development. Ten case or case-reference reports have been published suggesting that compared with reference populations, a higher proportion of children with imprinting diseases were conceived by assisted reproductive technologies. These reports are inconsistent in linking the risk to a specific assisted reproductive technology, and a cytogenetic examination assessing the exact genetic imprinting mechanism was not always provided. Two national systematic follow-up studies on 6052 Danish and 16,280 Swedish in-vitro fertilization children found none and two children with imprinting diseases, respectively. These figures correspond approximately to the expected number of children with imprinting disease from the general population. SUMMARY: The evidence of an increased risk of imprinting diseases in children conceived by assisted reproductive technologies is limited. The published case reports, however, call for a systematic multinational long-term follow-up of children born after assisted reproductive technologies.

Animals↗

Representations of reproductive technology in women's narratives of infertility.

This paper explores the ways in which the notion of reproductive technology is represented in the narratives of infertility told by a sample of Australian women. These narratives suggest that reproductive technology has been configured as the alternative instrument in realising the quest for a child. Because reproductive technology was represented in complex and changing ways in the narratives of individual women, it would have been inappropriate to divide the women into two groups as users and non-users of reproductive technology. The women were consulted at each stage of the research to ensure that what was inferred from their stories remained true to their narrative construction of themselves.

Adult↗

The new reproductive technologies: defying God's dominion?

Objections that the New Reproductive Technologies pose temptations to "play God" are common. This essay examines three versions of the objection: 1) these technologies "usurp God's dominion in reproduction"; 2) they permit us to "make" our offspring; and 3) they involve us in a denial of human finitude. None proves to generate a decisive case against the New Reproductive Technologies; each requires some further argument to be persuasive. Nonetheless, warning not to "play God" are shown to have an important parenetic function in the debate over medically-assisted reproduction, occasioning needed reflection on the meaning of creatureliness, finitude and responsible co-creation in the context of new forms of reproduction.

Catholicism↗

Social aspects of the new assisted reproduction technologies: attitudes of Israeli gynecologists.

AIM: To evaluate attitudes of gynecologists as to the social aspects of assisted reproduction technologies. METHODS: The survey was sent electronically to 600 gynecologists covering their opinions on impact of reproductive technologies, the role of gynecologists in reshaping social reality, their definition of family, concern for the unborn child, accessibility to the new technologies, and potential partners in the decision-making process. RESULTS: One hundred fifty-five gynecologists completed the questionnaire. The majority agreed that the new reproduction technologies have major social consequences (90.3%); that gynecologists, by putting these technologies to use, play a major role in changing social reality; and that the interests of the unborn child should be taken into consideration (84.5%). More than half included single parents and same-sex couples in the definition of a "family" and believed that fertility treatments should be available to everyone. As to sharing responsibility, 65.2% (n = 101) felt the gynecologist should not be the sole decision-maker regarding the necessity of treatment; among them, 49.7% preferred that social workers or psychologists be involved--rather than jurists. CONCLUSIONS: The gynecologists in the present survey seemed to be well aware of the importance of the social revolution initiated by the development of assisted reproduction technologies. While they accepted a broader definition of the family, they have not lost sight of the rights of the unborn child and as such, the need for related professionals to take a greater part in the decision-making process. These findings have important implications for educational programs in the health care professions and for future legislation regarding public accessibility to these procedures.

Attitude of Health Personnel↗

Can varicocelectomy significantly change the way couples use assisted reproductive technologies?

PURPOSE: We assessed how varicocelectomy alters semen quality in a large cohort of infertile men and determined whether it can change patient candidacy for assisted reproductive technology procedures. MATERIALS AND METHODS: A cohort of 540 infertile men with clinical palpable varicocele underwent microsurgical varicocelectomy and were followed more than 1 and 2 years postoperatively for alterations in semen quality and conception, respectively. Preoperatively and postoperatively the total motile sperm count was calculated in all semen analyses. Based on total motile sperm count values patients were divided into 4 groups according to the type of assisted reproductive technology for which they qualified, including 0 to 1.5 million or less (intracytoplasmic sperm injection candidates), 1.5 to 5 million or less (in vitro fertilization candidates), 5 to less than 20 million (intrauterine insemination candidates) and 20 million or greater sperm (spontaneous pregnancy candidates). Preoperative and postoperative semen quality was compared among individuals in these cohorts to determine the shifts in assisted reproductive technology care that are possible after varicolectomy. RESULTS: Mean patient age was 29.5 years (range 18 to 58). Microsurgical varicocelectomy was bilateral in 393 patients (73%), on the left side in 146 (27%) and on the right side in 1 (0.2%). A positive response to varicocelectomy, defined as a greater than 50% increase in total motile sperm count, was observed in 271 patients (50%). An overall spontaneous pregnancy rate of 36.6% was achieved after varicocelectomy with a mean time to conception of 7 months (range 1 to 19). Of preoperative in vitro fertilization and intracytoplasmic sperm injection candidates 31% became intrauterine insemination or spontaneous pregnancy candidates after varicolectomy. Of intrauterine insemination candidates 42% gained the potential for spontaneous pregnancy. CONCLUSIONS: Varicocelectomy has significant potential not only to obviate the need for assisted reproductive technology, but also to down stage or shift the level of assisted reproductive technology needed to bypass male factor infertility.

Adolescent↗

Current reproductive technologies: increased access and choice?

This article discusses key issues related to current reproductive technologies including contextual and personal barriers to use, complexity of decision making, limited access to technologies for poor women and women of color, and the politics and social controversy surrounding this area. New reproductive technologies have to be put to the same test as any other product--can and will women use them correctly? We need to not only know about the technology itself; we also need to know about the individuals who intend to use the technology and about contextual factors that influence use. Accordingly, the articles in this issue focus on the multiple determinants that influence acceptability of reproductive technologies and the policy, political, and legal implications associated with their use.

Abortion, Induced↗

Moral traditions, ethical language, and reproductive technologies.

The Vatican Instruction on reproductive technologies and the OTA report, Infertility, both use "rights" language to advance quite different views of the same subject matter. The former focuses on the rights and welfare of the embryo, and the protection of the family, while the latter stresses the freedom and rights of couples. This essay uses the work of Alasdair MacIntyre and Jeffrey Stout to consider the different traditions grounding these definitions of rights. It is proposed that a potentially effective mediating language could be that of "human nature", and argued that donor methods raise more serious moral objections than homologous ones.

Catholicism↗

Effect of repeated assisted reproductive technology on ovarian response.

PURPOSE OF REVIEW: Based on current rates of success, many infertile couples who desire pregnancy have to undergo repeated cycles of assisted reproductive technology. Concern has been raised that repeated cycles of assisted reproductive technology may have a detrimental effect on future ovarian response and function, as well as pregnancy. This review summarizes current knowledge of the effects of repeated assisted reproductive technology, highlighting recent publications. RECENT FINDINGS: The available published evidence so far indicates that the follicular response and the number of oocytes retrieved appears to be maintained with repeated treatment and the only significant decline in ovarian response is because of an increase in female age. Similarly pregnancy and live birth rates decline to a small degree only up to cycle 3 or 4, with increasing female age again being the prime determinant. Encouraging patients to undertake repeated treatment without undue delay leads to improved cumulative rates of pregnancy and live birth. Current evidence does not indicate that ovarian stimulation leads to an increased risk of ovarian malignancy. SUMMARY: Couples should be counselled from the outset that assisted reproductive technology treatment is a continuum and a number of treatment cycles may be necessary. At present, there is little indication that repeated cycles have a detrimental effect on ovarian function, although the outcome of further research is awaited.

Female↗

Assisted reproductive technologies: estimates of their contribution to multiple births and newborn hospital days in the United States.

OBJECTIVE: Estimate the contribution of assisted reproductive technology (ART) in the United States to multiple gestation births and newborn hospital days. DESIGN: Analysis of successful ART conceptions occurring during 1990 to 1991 compared with vital statistics. Newborn hospital days are estimated from the 1990 National Hospital Discharge Survey. SETTING: The American Fertility Society and the Society for Assisted Reproductive Technology registry. PATIENTS: Infants delivered from ART. INTERVENTIONS: Assisted reproductive technology. MAIN OUTCOME MEASURES: Number of multiple gestation infants and newborn hospital days. RESULTS: Approximately 12,327 live-born infants were delivered from ART conceptions during 1990 to 1991, representing 22.2% of all live-born triplet, 17.3% of quadruplet, and 11.4% of quintuplet infants born in the United States. The number of newborn hospital days attributed to ART infants was 87,135 days. Between the periods 1972 through 1974 and 1990 through 1991, the rate of triplet and higher order multiple gestation infants per 100,000 white live births increased by 191%, with 38% due to ART conceptions and 30% to increased childbearing among older women. CONCLUSIONS: Assisted reproductive technology contributed 22% of U.S. triplet and higher order multiple births during 1990 to 1991.

Female↗

Correct coding for laboratory procedures during assisted reproductive technology cycles.

New Current Procedural Terminology (CPT) codes for 2004 have been adopted for utilization with assisted reproductive technologies. It is important for professionals in the field of assisted reproductive technology (ART) to become familiar with them prior to their implementation. This document replaces the July 2002 American Society for Reproductive Medicine (ASRM) Practice Guideline Correct Coding for Laboratory Procedures During Assisted Reproductive Technology.

Clinical Laboratory Techniques↗

Correct coding for laboratory procedures during assisted reproductive technology cycles.

New Current Procedural Terminology (CPT) codes for 2004 have been adopted for utilization with assisted reproductive technologies. It is important for professionals in the field of assisted reproductive technology (ART) to become familiar with them prior to their implementation. This document replaces the July 2002 American Society for Reproductive Medicine (ASRM) Practice Guideline Correct Coding for Laboratory Procedures During Assisted Reproductive Technology.

Cell Culture Techniques↗

Correct coding for laboratory procedures during assisted reproductive technology cycles.

New Current Procedural Terminology (CPT) codes for 2004 have been adopted for utilization with assisted reproductive technologies. It is important for professionals in the field of assisted reproductive technology (ART) to become familiar with them prior to their implementation. This document replaces the July 2002 American Society for Reproductive Medicine (ASRM) Practice Guideline Correct Coding for Laboratory Procedures During Assisted Reproductive Technology.

Clinical Laboratory Techniques↗

Is there increased monozygotic twinning after assisted reproductive technology?

Over the past two decades there has been an association between assisted reproductive technologies and increased monozygotic twinning. The association is not clear nor are the causes of assisted reproductive technology-related monozygotic twinning understood, although there are several theories as to the possible mechanisms involved. This review looks at some of the assisted reproductive technologies which may be associated with an increased risk of monozygotic twinning such as intracytoplasmic sperm injection, assisted hatching and blastocyst transfers. Determining the true incidence of monozygotic twinning after assisted reproductive technologies is important as there is a well-documented increase in perinatal morbidity and mortality of monozygotic twins compared to singleton and dizygotic pregnancies.

Adult↗