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Has clinical practice been changed by the Human Fertilisation and Embryology Act 1990?

The birth in 1978 of the first baby to be conceived through in vitro fertilization caused both wonder and controversy. Concerns that this technology would be abused led the Government of the United Kingdom to appoint a Committee of Enquiry into human fertilization and embryology, which led to the publication in 1984 of what has become known as the Warnock Report. This made recommendations on the creation of human embryos in vitro, the storage of human eggs, sperm and embryos, and research on human embryos. This report led eventually to the passing by Parliament of the Human Fertilisation and Embryology Act 1990 and the creation of the Human Fertilisation and Embryology Authority, which since 1991 has licensed and regulated all centres and practitioners of assisted reproductive technology. The effects of these regulations are considered in this article. Clinical practice has been affected by the Act, but it has generally led to higher standards of clinical and laboratory practice, improved patient information and care, and improved ethical standards.

Journal Article↗

A proposed draft protocol for the European Convention on Biomedicine relating to research on the human embryo and fetus.

The objective of this paper is to stimulate academic debate on embryo and fetal research from the perspective of the drafting of a protocol to the European Convention on Biomedicine. The Steering Committee on Bioethics of the Council of Europe was mandated to draw up such a protocol and for this purpose organised an important symposium on reproductive technologies and embryo research, in Strasbourg from the 16th to the 18th of December 1996.

Embryo Research↗

Semen retrieval and analysis in men with myelomeningocele.

The introduction of advanced assisted reproduction technologies (ART) has created opportunities for the treatment of infertility among patients with myelomeningocele (MMC). The aim of this study was to assess the possibility of semen retrieval and to analyse the semen quality in men with MMC. Nine men, aged 22 to 39 with MMC participated in the study. Two participants were able to achieve unassisted ejaculation. Vibratory stimulation was unsuccessfully attempted in the remaining seven participants who then underwent electroejaculation under general anaesthesia. In total, enough spermatozoa for intracytoplasmic spermatozoa injection were retrieved from five participants. In four cases, no spermatozoa were observed in the ejaculates. Testicular biopsies, however, revealed spermatogenesis, and thus a reproductive potential, in one of these men. Therefore, in six of the nine men with MMC, fatherhood seemed possible with modern ART, despite the semen quality generally being very poor.

Adult↗

Ethics and embryos.

In this paper we argue that the human form should be seen to exist, in a longitudinal way, throughout the continuum of human growth and development. This entails that the moral value of that form, which we link analytically to the adult, interacting, social and rational being, attaches to all phases of human life to some extent. Having established this we discuss the consequences it has for the moral status of the human embryo. We then apply this argument, and the resulting moral status, to the area of reproductive technology. In doing this we show that there are certain regulations and controls which ought to apply to the use of these infertility treatments.

Abortion, Induced↗

Transmissions of hepatitis C virus during the ancillary procedures for assisted conception.

Since mother to child transmissions of hepatitis C virus (HCV) have been reported to be low, teams involved in assisted reproductive technologies have accepted HCV positive patients into their programmes. We report in the present paper two cases of undoubted patient to patient HCV transmission while patients were attending for assisted conception. In both cases, HCV genotyping and sequencing of the first hypervariable region of the HCV genome provided molecular evidence for nosocomial transmission. Investigations made to elucidate the route of contamination have shown that the most likely route of contamination is through healthcare workers. Such nosocomial HCV infection has been reported in other healthcare situations, mainly in dialysis units, and physical proximity was also suspected to be at the origin of the infection. We conclude that assisted reproduction teams must be very prudent when including such patients in their programmes.

Adult↗

Radiation damage to the uterus -- review of the effects of treatment of childhood cancer.

At the present time approximately 1 in 1000 young people aged between 16 and 35 years will have been cured of cancer in childhood and some of the treatment regimens used will have predictable effects on their future fertility prospects. In young women who have been exposed to radiotherapy below the diaphragm, the reproductive problems include the risk of ovarian failure and significantly impaired development of the uterus. The magnitude of the risk is related to the radiation field, total dose and fractionation schedule. Premature labour and low birth weight infants have been reported after flank abdominal radiotherapy. Female long-term survivors treated with total body irradiation and marrow transplantation are also at risk of ovarian follicular depletion and impaired uterine growth and blood flow, and of early pregnancy loss and premature labour if pregnancy is achieved. Despite standard oestrogen replacement, the uterus of these young girls is often reduced to 40% of normal adult size. Uterine volume correlates with the age at which radiation was received. Regrettably, it is likely that radiation damage to the uterine musculature and vasculature adversely affects prospects for pregnancy in these women. It has been demonstrated that, in women treated with total body irradiation, sex steroid replacement in physiological doses significantly increases uterine volume and endometrial thickness, as well as re-establishing uterine blood flow. However, it is not known whether standard regimens of oestrogen replacement therapy are sufficient to facilitate uterine growth in adolescent women treated with total body irradiation in childhood. Even if the uterus is able to respond to exogenous sex steroid stimulation, and appropriate assisted reproductive technologies are available, a successful pregnancy outcome is by no means ensured. The uterine factor remains a concern and women who are survivors of childhood cancer and their carers must recognize that these pregnancies will be at high risk.

Abortion, Spontaneous↗

Customizing conception: a survey of preimplantation genetic diagnosis and the resulting social, ethical, and legal dilemmas.

One in six American couples experience difficulties conceiving a child. With fertility rates at an all time low, the business of treating infertility is booming. However, due to the United States prohibition on government funding for embryonic research, the $4 billion industry of assisted reproductive technologies (ART) has been incompletely monitored and largely removed from oversight. Additionally, due to the fervent abortion debate, in vitro fertilization (IVF) was introduced in the United States without a research phase and procedures have been forced to evolve in the private sector. Thus, the checks and balances on medical innovation that are generally imposed by the federal government for consumer protection are lacking. Decisions about when to go from the laboratory to the clinic are often left solely to the discretion of private physicians. Preimplantation genetic diagnosis (PGD) is just one of many such treatments offered by these clinics. This iBrief examines how, why, and to whom the reproductive procedure of PGD is offered. In addition, it evaluates the prospective effects to society that arise when PGD is used for sex selection and for nontherapeutic or enhancement purposes. Finally, it explores whether and how to regulate PGD in the United States by investigating approaches to policy making that have been adopted by the United Kingdom.

Advisory Committees↗

The Canadian Birth Data Base: a new research tool to study reproductive outcomes.

A new tool for epidemiological, demographic, and genetic research--the Canadian Birth Data Base-is being developed at Statistics Canada. Over a million live birth and stillbirth records for the period 1987-89 received from all provincial and territorial offices of vital statistics are being processed in a form suitable for linkage with other files. Maternal, child health, occupational, and environmental concerns, as well as some of the consequences and possible risks involved in new reproductive technologies, could be investigated. Associations between socio-economic indicators (e.g., parental income, education, and occupation) and unfavourable birth outcomes could also be studied in the future. Approved statistical studies can be carried out within Statistics Canada on a cost-recovery basis. It is planned to update the data base annually.

Birth Certificates↗

The present status of management for infertility in Miyagi Prefecture, Japan.

To summarize the current management of infertility in Japan, a questionnaire survey was administered. A mail-survey method was used, and surveys were sent to 126 obstetrical and/or gynecological medical facilities in Miyagi Prefecture. The respondents included 86 facilities (68.3%). The majority of participants employed routine assessments, and their records included basal body temperature (98.8%), semen analysis (88.8%), and tubal patency tests (78.8%). Laparoscopic diagnosis, however, was uncommon (15.8%). With respect to treatment, surgical procedures, especially endoscopic procedures, were not generally carried out in addition to medicinal treatment. Sixty-one percent of the respondents performed intrauterine insemination, however assisted reproductive technology (ART) was provided by a few participants, for example, in vitro fertilization-embryo transfer was available at 11.3% of facilities. In self-assessment, the median pregnancy rates for the group undergoing laparoscopy and that not were significant different (30% and 20%, respectively), and those of the group undergoing ART provided and that not were significant different (35% and 20%, respectively). In conclusion, there are various differentials in the methods of diagnosis and treatment of infertility in the medical facilities today, and the outcomes are not always satisfactory. For appropriate management of infertile couples, it will be necessary to more closely manage cooperation between primary care doctors and reproductive specialists.

Adult↗

Investigation of the infertile couple: should diagnostic laparoscopy be performed after normal hysterosalpingography in treating infertility suspected to be of unknown origin?

Traditionally, a diagnosis of unexplained infertility is established only when all standard clinical investigations yield normal results. When tubal patency has been established by hysterosalpingography (HSG), laparoscopy has been suggested as a mandatory step to preclude the existence of peritubal adhesions and endometriosis as causes of infertility. In women without a previous history suggestive of tubal disease and who have a normal HSG, it was demonstrated that the probability of clinically relevant tubal disease or endometriosis is very low and that laparoscopy does not seem justified or cost effective. In the minority of these cases, laparoscopy might reveal minimal or mild endometriosis or peritubal adhesions. In these cases, either surgery or medical treatment has not been proven to improve fecundity. With the current success rates of assisted reproductive technologies (ART) and the relatively low contribution of diagnostic laparoscopy to the decision-making process of treating patients with a normal HSG, we suggest that laparoscopy should be omitted in couples suspected of having unexplained infertility. These patients should be treated by 3-6 cycles of combined gonadotrophins and intrauterine insemination, and if unsuccessful switched to ART.

Endometriosis↗

Infertility in Poland--present status, reasons and prognosis as a reflection of Central and Eastern Europe problems with reproduction.

Poland has been considered a representative country for the population of Central and Eastern Europe as it has genetically homogenous population and reveals profound similarities in economical and historical processes common for all countries of the region. According to our observations there is approximately 20% of infertile couples in Poland (lack of concentration after at least 12 month of unprotected intercourse) and 40-60% of them are infertile because of the male factor. However, studies of infertility in Poland that have been conducted so far need to be verified. The changes connected with the style of life and new tendencies observed during the tedious political changes had considerable influence on childbearing rate in Poland. Additional factors diminishing the fertility rate are: the change of the status of women in a society, raising amount of everyday stress, the high rate (17%) of unemployment and the low average income. Furthermore, in Poland, the diagnostics and treatment (assisted reproductive technology) are entirely financed from the private funds of a patient. Summing up, the problem of childlessness in Central and Eastern Europe is a complex one and very alarming therefore it is necessary to work out and to implement research, preventative and therapeutic programmes strengthened through the international cooperation of specialized centers of excellence.

Adolescent↗

The effects on offspring of premature parturition.

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and hearing loss, as well as reduced neuropsychological abilities, leading to deficient academic achievement and deterioration of several aspects of health status, are still highly prevalent among the most immature children. Interestingly, decreasing mortality rates, which are not followed by detectable increases of disability, are being observed in recent years. Future advances may be expected from clinical and basic research on uterine contractility and cervical softening. Also, changes in reproductive technology procedures, a main factor in the incidence of multiple pregnancies, and a more refined approach to obstetric care, compose some of the clinical interventions which may reduce the problem.

Developed Countries↗

In vitro and xenogenous capacitation-like changes of fresh, cooled, and cryopreserved stallion sperm as assessed by a chlortetracycline stain.

Like the human female, the mare experiences reproductive tract pathology that may sometimes be circumvented by the use of assisted reproductive technologies (ARTs). One such technology, gamete intrafallopian transfer (GIFT), may be used in mares that exhibit ovulatory, oviductal, or uterine abnormalities that limit the use of common ARTs, such as embryo transfer. Homologous GIFT has been successfully performed in the horse; however, the logistics, costs, and associated risks of surgically transferring gametes to the oviducts of a recipient mare are considerably high. Use of a less costly species in a heterologous or xenogenous procedure would therefore be beneficial. This study represents the preliminary investigation into the use of sheep as recipients for xenogenous GIFT procedures using equine gametes. We investigated the capacitation response of fresh, cooled, or frozen stallion sperm after 1) in vivo incubation in the reproductive tract of estrous and anestrous ewes as well as 2) in vitro incubation in a modified Krebs/ Ringer extender at 37 degreesC with and without the addition of heparin at 10 IU/mL for up to 8 hours. A chlortetracycline (CTC) fluorescent stain was used to assess the capacitation response of sperm. Findings indicated that oviductal fluid samples recovered from estrous ewes had significantly higher numbers of sperm exhibiting capacitation-like staining patterns when compared to samples recovered from anestrous ewes (P < .05). Fresh semen yielded higher capacitation-like staining patterns after in vivo incubation than did frozen-thawed or cooled samples. A transition from majority CTC unreacted sperm to majority CTC non-acrosome intact sperm was demonstrated for both in vivo and in vitro studies. In vitro incubation of stallion sperm with heparin did not result in an increased capacitation-like staining response over time when compared with nonheparinized samples. Results from this study suggest that xenogenous capacitation of stallion sperm may occur in the estrous ewe.

Anestrus↗

Cumulative number and morphological score of embryos resulting in success: realistic expectations from in vitro fertilization-embryo transfer.

OBJECTIVE: To define statistical thresholds for the number and morphological score of embryos transferred that would be predictive of reproductive success in an IVF program. DESIGN: A retrospective review of patient records. SETTING: The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS: One hundred women who underwent IVF-ET for a diagnosis of tubal occlusion and later delivered viable infants. RESULTS: The mean number of embryos transferred before achieving live birth was 10.7 +/- 7.9 (mean +/- SD), with one half of patients achieving success within the first seven embryos transferred, and 95% achieving success within 25 embryos. For high quality embryos, the numbers were 7.5 +/- 6.3, 5, and 17, respectively, and, for the cumulative embryo score, a measure of both embryo morphology and metabolic activity, were 114.2 +/- 86.0, 83, and 280, respectively. Greater than 50% of live births occurred within the first two ET attempts. CONCLUSIONS: Although more than half of patients achieved reproductive success within the first two ETs and the first five high quality embryos transferred, after this threshold, fecundity declined rapidly. The calculation of cumulative embryo scores offered additional prognostic information. While all prior attempts to define IVF-ET failure have done so by including patients who did not become pregnant, we have found an analysis of our successes to be a useful adjunct in counseling patients.

Adult↗

Assisted reproduction developments in the Islamic world.

A November 2000 workshop organized by the International Islamic Center for Population Studies and Research, Al-Azhar University, Cairo, considered use of assisted reproduction technologies (ART) in the Islamic world. The workshop reinforced a 1997 recommendation that a Standing Committee for Shari'a Medical Ethics be constituted to monitor and assess developments in ART practice. Among issues the workshop addressed were equitable access to services for infertile couples of modest means, and regulation of standards of equipment and personnel that ART centers should satisfy to gain approval to offer services. Acceptable uses of preimplantation genetic diagnosis were proposed, and follicular maturation research in animals, including in vitro maturation and in vitro growth of oocytes, was encouraged, leading to human applications. Embryo implantation following a husband's death, induced postmenopausal pregnancy, uterine transplantation and gene therapy were addressed and human reproductive cloning condemned, but cloning human embryos for stem cell research was considered acceptable.

Animals↗

Modern approaches to the treatment of human infertility through assisted reproduction.

Medical statistics from the United States show approximately 15 percent of all couples of reproductive age are unable to conceive naturally. In recent years, the numbers of couples with reproductive problems has increased, principally due to changes in life style and delayed childbearing. Only 13 years after the birth of the first "test tube baby", advances in the field of human reproduction have created a wide range of alternatives to help infertile couples conceive a healthy infant. Together, these techniques are called Assisted Reproductive Technology (ART) and include: in vitro fertilization (IVF), intratubal transfer of gametes (GIFT), intratubal transfer of zygotes (ZIFT), tubal transfer of preimplantation embryos (TET), gamete or embryo donation, cryopreservtion, and micromanipulation. The application of these techniques is presented here. While much remains to be learned, the ability to fertilize ova in vitro and sustain early embryonic life outside the body is now a reality. Contrary to the idea that these techniques create life in vitro, they simply remove barriers caused by different forms of infertility which impede the creation of life. More than 30,000 infants have now been produced world-wide through ART. In the future, new developments in the field of assisted reproduction promise to bring new hope to the growing numbers of infertile couples around the world.

Female↗

[Genetics of male sterility].

Infertility affects 10 to 15% of all couples, the man responsible being in approximately half of the cases. With the development of assisted reproductive technologies such as ICSI (Intracytoplasmic Sperm Injection), some infertile men can reproduce and transmit the infertility to their offspring. The genetic basis of male infertility has been extensively studied these last years. This article gives a non exhaustive overview of genetic defects associated with infertility, and emphasizes the importance of genetic screening, and possibly genetic counseling for these infertile males.

Chromosome Aberrations↗

The effect of various infertility treatments on the risk of preterm birth.

BACKGROUND: The high incidence of preterm birth (<37 weeks gestation) is a major concern in assisted reproductive technology. The objective of this study was to compare the risk of preterm birth from singleton pregnancies following either low technology treatment (intrauterine insemination and donor insemination) or high technology treatment (IVF, ICSI and gamete intra-Fallopian transfer) with that of naturally conceived pregnancies. METHODS: Three cohorts of pregnancies resulting from either low or high technology treatment or from natural conception were included in the study. A number of potential risk factors were adjusted for. RESULTS: The incidence of very preterm birth (<32 weeks of gestation) was not significantly increased in the low technology treatment group (1.0 versus 1.3% in controls) but was significantly higher in the high technology treatment group (5.2%, P < 0.001). In spontaneous, elective Caesarean section (CS) and induced delivery onset, the risk of preterm birth increased gradually from the controls to the low technology treatment group to the high technology treatment group, while for an emergency CS the risk of preterm birth was very high in both treatment groups. CONCLUSIONS: The overall incidence of preterm birth increased significantly from the controls to the low technology treatment group and to the high technology treatment group. Logistic regression analysis showed that younger and older age, previous perinatal death and emergency CS were associated with an increased risk, while a previous live birth reduced the risk. The length of the infertile period did not seem to affect the risk in any of the treatment groups.

Cesarean Section↗