be screened for evidence of carriage of hepatitis B virus his serum had not been tested for hepatitis B surface antigen and hence his carrier state was not known. Infection with hepatitis B virus is a recognised hazard for health care workers,2 and in future vaccine should be available for all those at risk of infection. This should considerably reduce if not eliminate the risk to staff and patients of nosocomial transmissions. With the current vaccines, however, the failure rate may be as high as 9% and a further 9% will have a low antibody response (< 10 mIU).3 Some of the non-responders will continue to be at risk and will require hepatitis B immunoglobulin after known exposures. Other non-responders will already be carriers. We suggest that the time has come to identify these non-responders as early as possible after infection so that they can be offered treatment and advice about their career. Treatment has a greater chance of success if given within two years of infection,4 and ideally hepatitis B carriers should be advised to choose a specialty that does not include surgery, obstetrics, or renal medicine. Vaccine should be available for all medical and dental students, and non-responders should be investigated and advised accordingly before firm choices of career have been made. The present policy of redeployment after known transmission to a patient5 could well be challenged in court not only when a surgeon is known to be a hepatitis B carrier but also if the carrier state is not excluded when there is no response to vaccine.
important to emphasise the need for flexibility with regard to this aspect of assisted conception lest the new authority becomes mesmerised by the data it has received to date. The rationale of limiting the number of oocytes or embryos to a finite number in all patients in the hope of achieving a singleton, as opposed to a multiple, pregnancy presupposes that all women have the same prospect of becoming pregnant or of having a multiple pregnancy. This is simply not so-for example, older women have a lower chance of becoming pregnant, and in women in whom gamete intrafallopian transfer is undertaken with suboptimal sperm fewer embryos will be generated. We have evaluated the results of transferring up to four oocytes in 349 gamete intrafallopian transfer cycles in women aged 40-45 in whom the outcome of pregnancy was known. There were no high order multiple births-that is, quadruplets or more-and the incidence of multiple pregnancy was 17% compared with 28-5% in those aged 39 or younger. The table indicates the numbers of pregnancies and deliveries associated with transferring one, two, or three oocytes when only this number were available and a maximum of four oocytes when four or more were available. We do not understand why anyone would wish to restrict the potential for pregnancy to a lower level when there is a minimal chance of a high order multiple birth. We have also reported other circumstances in which flexibility is required.2 We accept that in most cases a limited number of oocytes or embryos is appropriate, but we trust that the Human Fertilisation and Embryology Authority will not act against the interests of some infertile couples but will allow the incorporation within any guidelines of an appropriate clause to cover all circumstances-that is, "except in exceptional circumstances." We strongly recommend that decisions relating to this aspect of treatment should be made by clinicians in conjunction with their embryologists and that these should be based on the biological and clinical variables for individual couples. It would be regrettable if infertile couples were to seek legal advice against the Human Fertilisation and Embryology Authority, whose role is to facilitate treatment and research.
1 Kennedy S. An elementary mistake? BMJ 1991;302:1614. (29 June.) 2 Polakoff S. Acute viral hepatitis B: laboratory reports 1980-4.
BMJ 1986;293:37-8. 3 Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N EnglJ Med 1986;315:209-14. 4 Thomas HC. Treatment of hepatitis B viral infection. In: Viral hepatitis and liverdisease. New York: Alan R Liss, 1988:817-22. 5 Department of Health. Chief medical ofjficer's letter. London: DoH, 1972. (CMO 25/72.)
***For reasons of confidentiality this letter is unsigned.
IAN CRAFT TALHA AL-SHAWAF
Limiting the number of oocytes and embryos transferred in GIFT and IVF
London Fertility Centre and Medicraft Services, London WIN I AF 1 Waterstone J, Parsons J, Bolton V. Elective transfer of two embryos. Lancet 1991;337:975-6.
SIR, -At the recent annual meeting of the Interim Licensing Authority the chairman recommended that the new Human Fertilisation and Embryology Authority coming into force on 1 August should adopt a guideline restricting the number of embryos and oocytes for transfer in in vitro fertilisation and gamete intrafallopian transfer to just two. Some fertility specialists have recommended reducing the present maximum from four to three or even two.' Although the present guidelines are not legally binding, we assume that any clinicians who transfer more than the definitive number selected will have their licence withdrawn even if they are not subject to potential prosecution. It is therefore extremely
2 Craft I. Factors affecting the outcome of assisted conception. BrMed Bull 1990;46:769-82.
Brittle diabetes SIR,-We were interested in Professor Robert Tattersall and colleagues' report on their 12 year follow up of patients with brittle diabetes' as we have also studied such patients, in Newcastle upon Tyne2 and London.3 Professor Tattersall's definition of a patient with brittle diabetes-one "whose life is constantly
No of oocytes transferred
No(%)ofcyclesresultingin pregnancy Outcome of pregnancy: Delivery Miscarriage Biochemical pregnancy only
1
2
3
4
23 (6-6) 2 (8-7)
55 (15-8) 5 (9-1)
46* (13 2) 5 (10-9)
201 (57-6) 46(22-9)
1(4-3)
1 (1.8) 2 2
(4-3)
21(10-4) 16 9
I
2 2 1
*Not included are 24 patients who had more than three oocytes recovered but in whom only three were transferred; four of them (16-6%) became pregnant.
BMJ
VOLUME
303
20 JULY 1991
GEOFFREY GILL
Diabetes Centre, Walton Hospital, Liverpool L9 IAE GARETH WILLIAMS
Outcome of 349 gamete intrafallopian transfer cycles related to number of oocytes transferred
No(%)of cycles
disrupted by episodes of hyper or hypoglycaemia, whatever the cause"-is in general use.4 Nevertheless, this definition is subjective and open to individual interpretation, and we are surprised that a single centre should identify 25 patients with brittle diabetes during a two year period. Our combined populations of such patients total 34"' and are the result of tertiary referrals from some 30 centres throughout the United Kingdom. The patients had outstandingly poor glycaemic control and a poor quality of life. Many spent several months each year in hospital and were unable to maintain full time employment or attendance at school. Most suffered hyperglycaemic instability with recurrent attacks of ketoacidosis. Psychosocial disturbances and factitious induction of disturbed glycaemic control were common and in some cases may have been primarily responsible for the "brittleness."2 5 7 The discrepancy between our small "national" group and the large "local" Nottingham group seems to be the lax inclusion criteria used by the Nottingham workers-that is, three or more admissions with ketoacidosis or three or more attendances at the casualty department with hypoglycaemia during the two year study. Though not representative of acceptable control, the minimum requirements for inclusion can hardly be described as "life disrupting" and are inconsistent with Professor Tattersall's own definition. In the United Kingdom as a whole the criteria would identify 2000 or more patients with brittle diabetes in any two years. Clinical experience and reported data do not support the existence of so many patients with life disrupting metabolic instability. Another unusual feature of the patients in Nottingham is the almost equal sex distribution; this is in contrast with the female predominance in most other British2 3and American series.' Indeed, the patients with recurrent ketoacidosis at Guy's"9 and Freeman Hospitals25 were all female and in their teens or 20s. Our impression of the Nottingham study is that many patients were classified as having brittle diabetes during self limiting episodes of disturbed control perhaps due to psychosocial problems. We believe that this label should be reserved for those whose lives are truly disrupted by glycaemic instability. The experience in Nottingham does, however, concur with ours in that the long term prognosis of brittle diabetes seems surprisingly good. Our follow up studies confirm that in most of these patients more "normal" diabetic behaviour returns spontaneously as the years pass.69
Department of Medicine, Royal Liverpool University Hospital, Liverpool 1 Tattersall R, Gregory R, Selby C, Kerr D, Heller S. Course of brittle diabetes: 12 year follow up. BMJ 1991;302:1240-3.
(25 May.)
2 Gill GV, Husband DJ, Walford S, Marshall SM, Home PD, Alberti KGMM. Clinical features of brittle diabetes. In: Pickup JC, ed. Brittle diabetes. Oxford: Blackwell, 1985:29-40. 3 Pickup J, Williams G, Johns P, Keen H. Clinical features of brittle diabetic patients unresponsive to optnimsed subcutaneous insulin therapy (continuous subcutaneous insulin infusion). Diabetes Care 1983;6:279-84. 4 Tattersall R. Brittle diabetes. Clin Endocrinol Metab 1977;6: 403-19. 5 Gill GV, Walford S, Alberti KGMM. Brittle diabetes-present concepts. Diabetologia 1985;28:579-89. 6 Gill GV. The outcome of brittle diabetes-a follow up study of young female diabetic patients with recurrent ketoacidosis. DiabeticMed 1990;7(suppl 1):25A. 7 Williams G, Pickup JC, Keen H. Continuous intravenous insulin infusion in diabetic patients unresponsive to continuous subcutaneous insulin infusion. Diabetes Care 1985;8:21-7. 8 Schade DS, Duckworth WC. In search of the subcutaneousinsulin-resistance syndromne. N EnglJ7 Med 1986;315:147-53. 9 Williams G, Pickup JC. The natural history of brittle diabetes. Diabetes Res 1988;7:13-8.
185
important to emphasise the need for flexibility with regard to this aspect of assisted conception lest the new authority becomes mesmerised by the data it has received to date. The rationale of limiting the number of oocytes or embryos to a finite number in all patients in the hope of achieving a singleton, as opposed to a multiple, pregnancy presupposes that all women have the same prospect of becoming pregnant or of having a multiple pregnancy. This is simply not so-for example, older women have a lower chance of becoming pregnant, and in women in whom gamete intrafallopian transfer is undertaken with suboptimal sperm fewer embryos will be generated. We have evaluated the results of transferring up to four oocytes in 349 gamete intrafallopian transfer cycles in women aged 40-45 in whom the outcome of pregnancy was known. There were no high order multiple births-that is, quadruplets or more-and the incidence of multiple pregnancy was 17% compared with 28-5% in those aged 39 or younger. The table indicates the numbers of pregnancies and deliveries associated with transferring one, two, or three oocytes when only this number were available and a maximum of four oocytes when four or more were available. We do not understand why anyone would wish to restrict the potential for pregnancy to a lower level when there is a minimal chance of a high order multiple birth. We have also reported other circumstances in which flexibility is required.2 We accept that in most cases a limited number of oocytes or embryos is appropriate, but we trust that the Human Fertilisation and Embryology Authority will not act against the interests of some infertile couples but will allow the incorporation within any guidelines of an appropriate clause to cover all circumstances-that is, "except in exceptional circumstances." We strongly recommend that decisions relating to this aspect of treatment should be made by clinicians in conjunction with their embryologists and that these should be based on the biological and clinical variables for individual couples. It would be regrettable if infertile couples were to seek legal advice against the Human Fertilisation and Embryology Authority, whose role is to facilitate treatment and research.
1 Kennedy S. An elementary mistake? BMJ 1991;302:1614. (29 June.) 2 Polakoff S. Acute viral hepatitis B: laboratory reports 1980-4.
BMJ 1986;293:37-8. 3 Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N EnglJ Med 1986;315:209-14. 4 Thomas HC. Treatment of hepatitis B viral infection. In: Viral hepatitis and liverdisease. New York: Alan R Liss, 1988:817-22. 5 Department of Health. Chief medical ofjficer's letter. London: DoH, 1972. (CMO 25/72.)
***For reasons of confidentiality this letter is unsigned.
IAN CRAFT TALHA AL-SHAWAF
Limiting the number of oocytes and embryos transferred in GIFT and IVF
London Fertility Centre and Medicraft Services, London WIN I AF 1 Waterstone J, Parsons J, Bolton V. Elective transfer of two embryos. Lancet 1991;337:975-6.
SIR, -At the recent annual meeting of the Interim Licensing Authority the chairman recommended that the new Human Fertilisation and Embryology Authority coming into force on 1 August should adopt a guideline restricting the number of embryos and oocytes for transfer in in vitro fertilisation and gamete intrafallopian transfer to just two. Some fertility specialists have recommended reducing the present maximum from four to three or even two.' Although the present guidelines are not legally binding, we assume that any clinicians who transfer more than the definitive number selected will have their licence withdrawn even if they are not subject to potential prosecution. It is therefore extremely
2 Craft I. Factors affecting the outcome of assisted conception. BrMed Bull 1990;46:769-82.
Brittle diabetes SIR,-We were interested in Professor Robert Tattersall and colleagues' report on their 12 year follow up of patients with brittle diabetes' as we have also studied such patients, in Newcastle upon Tyne2 and London.3 Professor Tattersall's definition of a patient with brittle diabetes-one "whose life is constantly
No of oocytes transferred
No(%)ofcyclesresultingin pregnancy Outcome of pregnancy: Delivery Miscarriage Biochemical pregnancy only
1
2
3
4
23 (6-6) 2 (8-7)
55 (15-8) 5 (9-1)
46* (13 2) 5 (10-9)
201 (57-6) 46(22-9)
1(4-3)
1 (1.8) 2 2
(4-3)
21(10-4) 16 9
I
2 2 1
*Not included are 24 patients who had more than three oocytes recovered but in whom only three were transferred; four of them (16-6%) became pregnant.
BMJ
VOLUME
303
20 JULY 1991
GEOFFREY GILL
Diabetes Centre, Walton Hospital, Liverpool L9 IAE GARETH WILLIAMS
Outcome of 349 gamete intrafallopian transfer cycles related to number of oocytes transferred
No(%)of cycles
disrupted by episodes of hyper or hypoglycaemia, whatever the cause"-is in general use.4 Nevertheless, this definition is subjective and open to individual interpretation, and we are surprised that a single centre should identify 25 patients with brittle diabetes during a two year period. Our combined populations of such patients total 34"' and are the result of tertiary referrals from some 30 centres throughout the United Kingdom. The patients had outstandingly poor glycaemic control and a poor quality of life. Many spent several months each year in hospital and were unable to maintain full time employment or attendance at school. Most suffered hyperglycaemic instability with recurrent attacks of ketoacidosis. Psychosocial disturbances and factitious induction of disturbed glycaemic control were common and in some cases may have been primarily responsible for the "brittleness."2 5 7 The discrepancy between our small "national" group and the large "local" Nottingham group seems to be the lax inclusion criteria used by the Nottingham workers-that is, three or more admissions with ketoacidosis or three or more attendances at the casualty department with hypoglycaemia during the two year study. Though not representative of acceptable control, the minimum requirements for inclusion can hardly be described as "life disrupting" and are inconsistent with Professor Tattersall's own definition. In the United Kingdom as a whole the criteria would identify 2000 or more patients with brittle diabetes in any two years. Clinical experience and reported data do not support the existence of so many patients with life disrupting metabolic instability. Another unusual feature of the patients in Nottingham is the almost equal sex distribution; this is in contrast with the female predominance in most other British2 3and American series.' Indeed, the patients with recurrent ketoacidosis at Guy's"9 and Freeman Hospitals25 were all female and in their teens or 20s. Our impression of the Nottingham study is that many patients were classified as having brittle diabetes during self limiting episodes of disturbed control perhaps due to psychosocial problems. We believe that this label should be reserved for those whose lives are truly disrupted by glycaemic instability. The experience in Nottingham does, however, concur with ours in that the long term prognosis of brittle diabetes seems surprisingly good. Our follow up studies confirm that in most of these patients more "normal" diabetic behaviour returns spontaneously as the years pass.69
Department of Medicine, Royal Liverpool University Hospital, Liverpool 1 Tattersall R, Gregory R, Selby C, Kerr D, Heller S. Course of brittle diabetes: 12 year follow up. BMJ 1991;302:1240-3.
(25 May.)
2 Gill GV, Husband DJ, Walford S, Marshall SM, Home PD, Alberti KGMM. Clinical features of brittle diabetes. In: Pickup JC, ed. Brittle diabetes. Oxford: Blackwell, 1985:29-40. 3 Pickup J, Williams G, Johns P, Keen H. Clinical features of brittle diabetic patients unresponsive to optnimsed subcutaneous insulin therapy (continuous subcutaneous insulin infusion). Diabetes Care 1983;6:279-84. 4 Tattersall R. Brittle diabetes. Clin Endocrinol Metab 1977;6: 403-19. 5 Gill GV, Walford S, Alberti KGMM. Brittle diabetes-present concepts. Diabetologia 1985;28:579-89. 6 Gill GV. The outcome of brittle diabetes-a follow up study of young female diabetic patients with recurrent ketoacidosis. DiabeticMed 1990;7(suppl 1):25A. 7 Williams G, Pickup JC, Keen H. Continuous intravenous insulin infusion in diabetic patients unresponsive to continuous subcutaneous insulin infusion. Diabetes Care 1985;8:21-7. 8 Schade DS, Duckworth WC. In search of the subcutaneousinsulin-resistance syndromne. N EnglJ7 Med 1986;315:147-53. 9 Williams G, Pickup JC. The natural history of brittle diabetes. Diabetes Res 1988;7:13-8.
185
