752 VALIDATED ESTIMATES OF INCIDENCE OF ANOREXIA NERVOSA
health district for coded true-first female admissions (to main serving hospitals) over 1979-84, was 3-16 unvalidated, 2-79 non-rejected, and 2.13 per 100 000 per annum for confirmed cases (diagnosis supported in case-notes either 6 months from onset or after 3 months of medical assessment). Williams and King tell us that it is wrong to speak of an epidemic of anorexia nervosa. Perhaps, but neither the condition itselfl.3 nor its causes7 show any signs of abating. 85A Pilton Street,
Barnstaple,
Devon EX32 1PQ
ROBERT REYNOLDS
J, Grossman S. Epidemiology of anorexia nervosa in a defined region of Switzerland. Am J Psychiatry 1983; 140: 564-67. 2. Crisp AH. Prevalence of anorexia nervosa. Br Med J 1978; ii: 500. 3. Theander S. Anorexia nervosa: a psychiatric investigation of 94 female patients. Acta Psychiatr Scand 1970; suppl 214: 1-194. 4. Kendell RE, Hall DJ, Hailey A, Babigian HM. The epidemiology of anorexia nervosa. Psychol Med 1973; 3: 200-03. 5. Jones DJ, Fox MM, Babigian HM. Epidemiology of anorexia nervosa in Monroe County, New York. Pyschosom Med 1980; 42: 551-58. 6. Szmukler G, McCance C, Hunter D. Anorexia nervosa: a psychiatric case register study from Aberdeen. Psychol Med 1986; 16: 49-58. 7. Kendell RE. The role of diagnosis in psychiatry. Oxford: Blackwell, 1975. 1. Willi
SIR,-Age-period-cohort (A-P-C) modelling is a powerful method for analysing a series of rates over time. The application of this method by Dr Williams and Dr King to admission rates for anorexia nervosa showed that recent increases in rates are attributable to changes in the age structure of the female population. In their A-P-C analysis Williams and King used an identification specification,l setting the first two cohort effects equal. This procedure is unnecessary since the objective was to test significance rather than estimate parameters. Cohort category is determined by age group and year, so one degree of freedom in the A-P-C model cannot be attributed uniquely to one of the classifications but is common to them all. If backward elimination is used to assess the significance of the main effects in the model, deletion of each in turn increases the degrees of freedom (DF) for the residual deviance by the number of categories in the variate omitted less two (rather than one as might be expected). There is one DF too few for the number of parameters to be estimated, and the identification specification is an approach to overcoming this difficulty. It is not clear whether backward elimination was used. Rates were analysed by single year of age in the range 10-24. So there are 15 age categories, but the table gives 13 DF in their table. This would be correct if backward elimination had been used. 10 periods are considered so backward elimination of year would give 8 DF (not 9). If the temporal increase in first admissions for women is due to changes in the age-structure alone then this could be demonstrated by comparisons of age-specific rates over time. MRC Unit for Epidemiological Studies In Psychiatry,
Royal Edinburgh Hospital, Edinburgh EH10 5HF 1.
JOHN C. DUFFY PAUL G. SURTEES
Fienberg SE, Mason WM. Identification and estimation of age-period-cohort models in the analysis of discrete archival data. In: Schuessler KF, ed. Sociological methodology. San Francisco: Jossey-Bass, 1979: 1-67.
**These letters have been shown to Dr Williams and Dr King, whose reply follows.-ED. L. SIR,-Dr Reynolds claims that we have neglected the likely impact of ICD-9. As indicated in our paper, there was no major change in the classification of eating disorders between ICD-8 and ICD-9. Furthermore, Kendell, analysing the change in 1981, found
not immediately led "to any major change in the diagnoses English psychiatrists give to their patients".’ As Reynolds notes, we did not take into account the treatment of anorexia nervosa in non-psychiatric settings. However, we did point out that anorexia nervosa in general practice samples is rare2,3 and few anorexics nowadays are managed in non-psychiatric specialist settings.4 Reynolds presents a table of figures from studies that we cited, purporting to show that the incidence of anorexia nervosa has increased. The studies cannot legitimately be compared with one another-one is from Scandinavia, another from Switzerland, and the other from Scotland, and two are based on routine statistics and the other on a case register. Also, the figures that Reynolds cites are not always the same as those quoted by the authors-for example, table 1 of Willi and Grossman’ gives incidence rates per 100 000 females of 3-98, 6-79, and 16-76 for the three time periods, respectively. Even so, Reynolds does not seem to appreciate that we do not dispute that there has been an increase in the incidence of anorexia nervosa-our study was concerned with trying to explain it. Reynolds refers, without supporting evidence, to "hesitation to admit young patients to general psychiatric wards". However, as we noted "changes in admissions policies over time would be represented in our analyses as a period effect". No such effect was
that it had
found.
Duffy and Surtees appear to be making a minor statistical point. Strictly speaking, equating two effects is unnecessary if parameter estimation is not to be undertaken. If it is done, 2 DF are lost when the significance of each main effect is tested using backward elimination (the method we used). 2 DF are lost if the equality constraint is applied to age when the effect of age is tested, to period when the effect of period is tested, and to cohort when the effect of cohort is tested. We applied the equality constraint to age (not cohort, as stated in the paper) for the entire analysis. However, it makes no important difference to the conclusion of our study whether effects are equated or not or, if they are, which effects are
equated. Institute of Psychiatry, London SE5 8AF
PAUL WILLIAMS MICHAEL KING
1. Kendell RE. The international classification and the diagnoses of English psychiatrists J 1968-1980. Br Psychiatry 1981; 139: 177-80. 2. King MB. Eating disorders in general practice. Br Med J 1986; 293: 1412-14. 3. Meadows GN, Palmer RL, Newball EUM, Kenrick JMT. Eating attitudes and disorder in young women: a general practice based survey. Psychol Med 1986; 16: 351-58. 4. Willi J, Grossman S. Epidemiology of anorexia nervosa m a defined area of Switzerland. Am J Psychiatry 1983; 140: 564-67.
BIRTH AFTER CRYOPRESERVATION OF UNFERTILISED OOCYTES
SIR,-Controversy over the cryopreservation of embryos may limit the application of this technique. The storage of frozen oocytes could be an alternative approach, however-with the added advantage that cryopreservation of oocytes might improve the prospects of fertility in young women scheduled to be treated by chemotherapy or radiotherapy for cancer. Because our freezing technique differs from the one described by Chen1 we felt that the second birth worldwide after oocyte cryopreservation would be of interest. In 1980, in an attempt to overcome cell damage due to supercooling, we started to experiment with an alternative technique for freezing embryos.2 This work led to the development of a computer-controlled "open vessel" freezing device (CTE 8100).3 This device, utilising tailed plastic straws, permits ice nucleation to take place automatically in the ideal temperature range around the freezing point of the medium ("self-seeding"). With the rapid-freeze and rapid-thaw technique 85-8% survival rate of frozen/thawed mouse embryos at various stages of cleavage and an 87-5% development rate in vitro were obtained.3,4 With the slow-freeze and slow-thaw procedure rates were even higher.56 This approach to human embryo freezing resulted in successful pregnancies.5,7
753
April, 1986, guidelines from the Bundesarztekammer (Federal Medical Council) have restrained the storage of human embryoso we began to apply the slow-freeze and slow-thaw technique to the preservation of excess human oocytes. In contrast to the results reported by Trounson and Mohr, 7 of the first series of 28 human oocytes survived freezing (25 %). Two patients were given embryos, transferred after in vitro fertilisation (IVF) of Since
cryopreserved oocytes, and one became pregnant. This 30-year-old woman with a long history of recurrent salpingitis and infertility was referred for IVF. After superovulation eight oocytes were recovered. Four were inseminated in vitro and embryos were transferred; no pregnancy ensued. The other four oocytes were reduced in size by needle dissection of the cumulus and incubated for 6 h. The freezing medium was phosphate-buffered saline (PBS) containing 10% heat-inactivated fetal cord serum (FCS) and 1-5 mol/I dimethylsulphoxide (DMSO). After addition of DMSO in 5 min step incubations of increasing concentrations at 37°C (0-25 mol/1 per step), the oocytes two
were allowed to incubate in the straws for another 55 min at 24OC.5,6.10 In the CTE 8100 freezing device the temperature was reduced from 24°C to zero at a rate of 2°C/min, and thereafter at rates of 1, 0-3, 0-2, 0-1, and 0-3°C/min to -2, -3, -4, -6, and —70°C, respectively. Self-seeding took place around -5°C. At - 70°C oocytes were transferred into liquid nitrogen. 3 months after the initial treatment cycle ovulation was induced with clomiphene citrate 100 mg daily from day 5 to day 9, and the cycle was monitored by measurement of oestradiol-17p and urine luteinising hormone (LH) levels, and by ultrasound. 1 day after the LH surge, oocytes were thawed by placing the straws at room temperature. DMSO was diluted by 0-25 mol/1 in 5 min steps at 37°C. After incubation for 5 min in PBS + 20 % FCS, the oocytes were placed for 2 h in Ham’s F10 medium+ 20% FCS before insemination. The next day two embryos were transferred in the pronuclear stage. The luteal phase was supported with human chorionic gonadotropin. A pregnancy was established and at 38 weeks’ gestation a healthy girl was born.
J. F. H. M. VAN UEM E. R. SIEBZEHNRÜBL B. SCHUH R. KOCH S. TROTNOW N. LANG
Department of Obstetrics and Gynaecology, University of Erlangen-Nuremberg, 8520 Erlangen, West Germany
or more of the respondents would wish to be tested, would know that the test was being done, and would want to know the result; fewer women said that they would request pregnancy termination if found positive; and fewer still would change their method of contraception: Would you wish to be tested at the booking clinic?- Yes 124 (81 % ) , No 20, Equivocal 2, Did not answer 7. If screening were introduced would you wish to know that it was being done-Yes 132 (86 %), No 6, Equivocal 8, Did not answer 7. If the test proved positive would you wish to know the result?- Yes 137 f’90% No 2, Equivocal 3, Did not answer 11. If found positive would you seek termination?- Yes 101 (66 % , No 18, Equivocal 24, Did not answer 10. If found positive would you change your method of contraception in future?-Yes 84 (55 % , No 41, Equivocal 6, Did not answer 22. Of the 41 who would not change their method of contraception, 21 were already using the sheath before conception, 6 would abstain from intercourse, and 6 thought it was too late to do anything; 8 gave no reason for not changing. Most patients surveyed had some knowledge of HIV and its implications during pregnancy. It would appear, however, that further counselling of pregnant patients will be required. Most pregnant women will accept screening, and for the minority who do not wish to know the result samples could be tested anonymously; in this way most women could be properly cared for while the minority would still contribute assessments of the incidence of HIV
80 %
want to
infection.
J. B. SCRIMGEOUR and Gynaecology, Western General Hospital, Edinburgh EH4 2XU
HAEMORRHAGE AT CAESAREAN SECTION
SIR,-Dr Axelsson and colleagues (March 7, p 563) describe tying a rubber tube around the cervix to stop bleeding in cases of massive haemorrhage during caesarean section. All that is required is direct compression of the aortal1 The Old
Rectory,
Bittadon,
Barnstaple, N Devon EX31 Pregnancy after human oocyte cryopreservation. Lancet 1986; i: 884-86. S, Silvassy B, Gorlach A. A new freezing-technique for embryos. Arch Androl 1980; 5 (suppl): A145. 3. Trotnow S, Siebzehnrübl E. Cryopreservation of mammalian embryos. In: Feichtinger W, Kemeter P, eds. Recent progress in human in vitro fertilisation. Palermo: Edizione Cofese, 1983: 307-19. 4. Siebzehnrübl ER. Die Kryokonservierung von Mauseembryonen mit dem automatisierten "Offenen System" mit Selbstseeding. Thesis, University of Erlangen-Nuremberg, 1984. 5. Siebzehnrübl E, Weigel M, Habermann P, van Uem J, Trotnow S. Cryopreservation of human embryos at the Erlangen University Women’s Hospital. JIVFET 1986;
M. GAUDOIN M. HOBSON R. NEILL M. PAPACHRYSOSTOMOU
Department of Obstetrics
JOHN MCGARRY
4HN
1. Chen C.
2. Trotnow
3: 68. 6. Al-Hasani S, Trotnow S, Barthel M. Kryokonservierung von Kaninchenembryonen des Acht-Zell-Stadiums in automatisierten "Offenen System". Geburtsh Frauenheilk 1982; 42: 848-52. 7. Siebzehnrubl E, Trotnow S, Weigel M, et al. Pregnancy after in vitro fertilization, cryopreservation, and embryo transfer. JIVFET 1986; 3: 261-63. 8. Vilmar K, WolffHP. Richtlinien zur Forschung an frühen menschlichen Embryonen. Deutsches Ärztebl 1985; 82: 3757-64. 9. Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature 1983; 305: 707-09. 10. Bank H, Maurer RR. Survival of frozen rabbit embryos. Exp Cell Res 1974; 89: 188-96.
SCREENING FOR HIV DURING PREGNANCY
Sip,—To find out patients’ views
on
antenatal
testing for HIV
infection a questionnaire was given to 170 women, to be completed
anonymously at booking and antenatal clinics during February, 1987. 153 patients completed the form. No patient admitted to being in a high-risk group for HIV infection but 10 (6-5 %) thought themselves to be at some risk-5 if they were to receive a blood transfusion; 2 were staff nurses, 1 was married to a hospital porter, and 1 was a hospital laboratory worker; and 1 gave no reason.
1. Anon. Report on confidential enquiries into maternal deaths in 1976-1978. London: HM Stationery Office : 38.
England and
Wales
ACTIVE MANAGEMENT OF LABOUR
SiR,—Dr Sheehan (March 7,
p 548) reports that the caesarean in nulliparae who were actively managed in an Irish hospital was lower than that in a similar group of nulliparae who were not actively managed in an American hospital (9-5 versus 20-2%). The conclusion was that no advantage to the infant results from the greater use of caesarean childbirth for dystocia and that the frequency of caesarean section could be safely reduced in nulliparae by 4-5 percentage points. In a controlled study in this hospital in 1984, the caesarean section rate was 6-0 % (n = 200) in actively managed nulliparae compared with 13 -0 % (n = 509) in nulliparae not actively managed (p < 0 O 1 ).1 Subsequently, the principles of active management of labour2 were applied in 68% of the nulliparae delivered in 1985. The introduction of active management was associated with a 4-5 % reduction in the caesarean section rate (table), without any increase in perinatal mortality, perinatal morbidity, birth trauma, or admissions to the neonatal unit.3 In the first 1200 nulliparae actively managed, the caesarean section rate for dystocia was 2-3%, which was identical to that for dystocia in a similar group of Irish nulliparae (n 2500) delivered in 1985 in the hospital where active management was pioneered.4 Furthermore, the caesarean section rates for dystocia were the same in the different ethnic groups in the London population.
section
rate
=