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Factors affecting the outcome of assisted conception.

In order to assess the major biological and clinical factors which influence the outcome of both IVF and GIFT, the results of a large GIFT series performed in this unit have been analysed over a time interval when two different policies have been in force as to the number of oocytes that should be transferred. The reason for using GIFT data, as opposed to IVF, is simply because it is more difficult to adversely affect the outcome of GIFT treatment, as opposed to IVF, and hence this allows more critical appraisal and interpretation of results. The GIFT series to be described was conducted between March 1986 and October 1987, when a flexible policy on the number of oocytes for transfer was in operation. Since then a fixed policy has been in force at the request of the Hospital's Ethics Committee and the Voluntary Licensing Authority (now the Interim Licensing Authority), whereby three, or exceptionally four, oocytes are transferred irrespective of individual patient's circumstances because of concern about the relative risk and sequelae of multiple pregnancy and selective reduction of pregnancy. I still believe, however, that some infertile couples have a lower chance of pregnancy with assisted, or natural conception and also a lower risk of multiple pregnancy and that it is therefore important to assess the biological and clinical factors influencing fecundity in order to formulate appropriate treatment policies.

Adult↗

Guidelines: egg donation and consent forms.

Egg donation has caused the Interim Licensing Authority concern in the last year. In its latest annual report it has issued additional guidelines on the subject. It has also issued a booklet 'Egg Donation: your questions answered' to be given to all prospective egg donors. The booklet contains a consent form for egg donation. The new guidelines and consent form are reproduced below. Also reproduced is the standard ILA consent form for in vitro fertilisation, which all licensed IVF units must use.

Consent Forms↗

A conversation with Dr Anne McLaren, DBE, DPhil, FRS, FRCOG.

Anne McLaren is one of the world's foremost developmental biologists; a leader in elucidating the principles of early mammalian development whose research has underpinned advances in reproductive medicine and the treatment of infertility. After undergraduate and postgraduate studies at Oxford University and postdoctoral work in London, she was for 15 years at the Institute of Animal Genetics in Edinburgh followed by 18 years as Director of the MRC Mammalian Development Unit in London. She is currently a Group Leader at the Wellcome Trust/Cancer Research UK Gurdon Institute in Cambridge. She was elected a Fellow of the Royal Society in 1975 and became the first woman to hold office in that Society - as Foreign Secretary, from 1991-1996. Dr McLaren played a pivotal role in the creation of the UK Human Fertilisation and Embryology Authority. She was a member of the Warnock Committee, served on the Voluntary (later Interim) Licensing Authority and was a key member of the HFEA from its establishment until the end of 2001. She chaired the Scientific and Technical Advisory Group of WHO's Human Reproduction Programme and is President of the Association of Women in Science and Engineering. She is a member of the European Group on Ethics that advises the European Commission on social and ethical implications of new technologies. In 2002, she was awarded (jointly with A. K. Tarkowski) the Japan Prize for Developmental Biology. She continues to have one of the sharpest minds in the business; for her, science has been not only a joy but an intellectual adventure of the highest order. She is interviewed here by Editorial Board Member Jane Denton.

Developmental Biology↗

Chromosomal analysis of human oocytes fertilized by microinjection of spermatozoa into the perivitelline space.

In-vitro fertilization by sperm microinjection techniques have been shown to be effective (the birth of one child has resulted), but concerns about the chromosomal normality of embryos derived from this process have been raised. The British Interim Licensing Authority has set, as a pre-condition to the clinical application of sperm microinjection, the chromosomal evaluation of pre-embryos derived by this technique. In this study, we demonstrate that four of 18 (22%) eggs fertilized by sperm microinjection into the perivitelline space are chromosomally abnormal as compared with nine of 30 (30%) fertilized by conventional IVF procedures. These results are not significantly different. In addition, we demonstrate that nine out of 20 couples who did not previously have fertilization in multiple cycles of IVF had between one and three oocytes fertilized by sperm microinjection. These findings demonstrate that sperm microinjection does not increase the incidence of chromosomally abnormal eggs and provide reassurance and support for the clinical implementation of a technique that appears to be effective for the treatment of certain forms of male infertility.

Aneuploidy↗

The influence of ovarian response on gamete intra-Fallopian transfer outcome in older women.

Fecundity declines with increasing age in women. The pregnancy rate is lower in in-vitro fertilization/embryo transfer (IVF/ET) in women aged greater than or equal to 40 years. We analysed 349 consecutive gamete intra-Fallopian transfer (GIFT) cycles in women aged greater than or equal to 40 years to identify factors which affected the outcome. A maximum of four oocytes were transferred in GIFT as recommended by the Interim Licensing Authority; 61 women (17.5%) had a positive serum beta-human chorionic gonadotrophin, 35 (10%) had a miscarriage and 26 (7.5%) delivered live infants. The pregnancy rate was lower than with younger women while the conception loss was higher. Pregnancy and delivery rates increased as the number of oocytes retrieved increased but declined again if greater than 10 oocytes were retrieved. If 1-3 oocytes were retrieved, the pregnancy rate was 9.7% and the delivery rate was 3.9%; if 4-10 oocytes were retrieved, the pregnancy rate was 22.1% and the delivery rate was 10.1%, and when greater than 10 oocytes were retrieved, the rates were 17.6 and 5.9% respectively. The highest pregnancy rate was when four oocytes were transformed in GIFT (22.4%) and the delivery rate was 10.0%. An adequate response to long down-regulation with gonadotrophin-releasing hormone agonist was also a factor associated with high delivery rates (13.5%). We conclude that the delivery rate after GIFT in women aged greater than or equal to 40 years is low, but there is a subgroup who have an acceptable delivery rate because of a good ovarian response. In this group, pituitary down-regulation improves the outcome of treatment.

Adult↗

Ethical and legal implications in IVF and prenatal diagnosis in the U.K.

The natural desire for couples to be parents and the medical practitioner's inability to treat most genetic diseases have been responsible for some of the most exciting research into infertility and genetic disorders. This has led in the United Kingdom to the establishment of the Warnock Committee of Inquiry into Human Fertilization and its report in 1984, and to a Review of the guidance on Research Use of Fetuses and Fetal Material published in 1989 and known as the Polkinghorne Report. The Warnock Report, among other ethical issues, considers the most fundamental question which has been debated for thousands of years, namely, What is life and when does it begin? More recently, the report has been responsible for new legislation which imposes ethical and legal restrictions on the scientific and medical community. The Polkinghorne Report recommends a voluntary code of practice which is morally and ethically acceptable within our society. We are also fortunate in the U.K. to have a parliamentary structure which allows debate on such important human issues and is prepared to impose ethical restrictions.

Abortion, Induced↗

Regulation before the HFEA.

As a result of the birth of Louise Brown, the Government, in 1982 set up the committee of Inquiry into Human Fertilisation and Embryology (The Warnock Committee). This committee made a number of recommendations including one that recommended the setting up of a body to regulate these procedures. The Medical Research Council and the Royal College of Obstetricians and Gynaecologists in the interim set up a voluntary body to regulate the centres doing IVF. This was called the Voluntary Licensing Authority (VLA) for Human in-vitro Fertilisation and Embryology. Centres were visited and licensed. This body regulated the centres until the statutory body the Human Fertilisation and Embryology Authority (HFEA) was formed in 1990.

Embryology↗

Medicare program; waiver requirements and solvency standards for provider-sponsored organizations--HCFA. Interim final rule with comment period.

This interim final rule with a request for comments implements authority to waive, in the case of provider-sponsored organizations (PSOs) that meet certain criteria, the requirement that Medicare + Choice organizations be licensed by a State as risk-bearing entities. The waivers will be approved only under certain conditions where the State has denied or failed to act on an application for licensure. This rule also establishes solvency standards that certain entities must meet to contract as PSOs under the new Medicare + Choice program. These standards apply to PSOs that have received a waiver of the requirement that Medicare + Choice organizations be licensed by a State as risk-bearing entities.

Centers for Medicare and Medicaid Services, U.S.↗