Does histological incomplete excision of cervical intraepithelial neoplasia following large excision of transformation zone increase recurrence rates? A six year cytological follow up

CORRESPONDENCE 771

not). Mirena, besides not being any more effective in preventing intra or extrauterine pregnancies when compared with any of the standard intrauterine systems containing more than 250mm 3 of copper (copper T 380 Ag and copper T 380A) 2, is also 11 times more expensive (£99 vs £9). There is in addition good evidence to show that the short, medium and long term patient dissatisfaction rate for Mirena, assessed by discontinuation as a result of systematic androgenic side effects, menstrual irregularities and expulsion are higher than with users of intrauterine systems with more than 250mm 3 of copper 3. The amenorrhoea produced by Mirena is not always a positive side effect as some women view regular menstruation as a sign of femininity which reassures them that they are neither pregnant nor menopausal. The intrauterine contraceptive device for women without menstrual problems should be standard copper T 380A and Copper T 380Ag, and not Mirena. If Mirena is to achieve its desired status as the intrauterine contraceptive system of choice it needs to compete in terms of cost, duration of contraceptive ef®cacy and increased tolerability.

References 1. French RS, Cowan FM, Maansour D, et al. Levonorgestrel-releasing (20ug/day) intrauterine systems (Mirena) compared with other methods of reversible contraceptives. Br J Obstet Gynaecol 2000;107:1218± 1225. 2. Nilsson CG, Allonen H, Diaz J, Luukkainen T. Two years experience with Levonorgestrel-releasing intrauterine devices and one copperreleasing intrauterine device: a randomised comparative performance study. Fertil Steril 1983;39:187±192. 3. Sivin I, Stern J. Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu 380 Ag intrauterine contraceptive devices: a multicenter study. International Committee for Contraceptive Research (ICCR). Fertil Steril 1994;61:70±77.

B. A. Onyeka Blackpool Victoria Hospital NHS Trust, Blackpool, UK PII: S 0306-545 6(00)00157-1

Authors uthors' Reply eply Sir, The aim of our systematic review was to investigate the contraceptive properties of Mirena. Our review of the literature to July 1998 showed no advantage of the Mirena intrauterine system compared with Copper T380 devices bearing copper bands on their side arms in terms of effectiveness and continuation rates. Moreover the latter are cheaper than the Mirena intrauterine systems (the December 2000 `MIMS' price of the newly marketed T-Safe 380A which replaces the Gyne T 380S withdrawn for purely commercial reasons in 1999 is £9.40, compared to £89.25 for the Mirena and can be used for at least eight years. A systematic review conducted by Lethaby et al. has investigated the evidence for the use of levonorgestrel-releasing systems for heavy menstrual bleeding 1. Current evidence suggests that the Mirena intrauterine system is effective and acceptable in the treatment of heavy menstrual bleeding. Using data derived from the randomised trial of Andersson et al. 2, Suvisaari and Lahteenmaki 3 demonstrated that, with the passage of suf®cient time since insertion, the initial mean increase in the duration of bleeding and

spotting actually reduces to less than the control population using a copper device. The 60 month termination rates for oligo-amenorrhea (a frequent occurrence which signi®es no pathology) in the multicentre study of Andersson et al. 2 aried from 1.7% in Sweden to 19.6% in Hungary (personal communication, I. Rauramo). This may suggest that the providers' attitudes (reassuring or otherwise) to users' reports of amenorrhea associated with the Mirena intrauterine system in¯uence continuation of the method. Moreover a recent nation-wide post-marketing study by Backman et al. 4 of 17,914 Finnish women demonstrated that occasional or totally missed menstruation was statistically associated with prolonged or continued use of the method (odds ratio 0.46, CI 0.43-0.5). Maintaining women's choice and autonomy makes it essential in advising women concerning intrauterine contraception.

References 1. Lethaby AE, Cooke I, Rees M. Progesterone/progestogen releasing intrauterine systems versus either placebo or any medication for heavy menstrual bleeding (Cochrane Review). The Cochrance Library. Issue 4. Oxford: Update Software, 2000. 2. Andersson K, Odlind V, Rybo G. Levonorgestrel-releasing and copperreleasing (Nova T) intrauterine devices during ®ve years of use: a randomised comparative trial. Contraception 1994;49:56±72. 3. Suvisaari J, Lahteenmaki P. Detailed Analysis of Menstrual Bleeding Patterns After Postmenstrual and Postabortal Insertion of a Copper IUD or a Levonorgestrel-Releasing Intrauterine System. Contraception 1996;54:201±208. 4. Backman T, Huhtala S, Blom T, Luoto R, Rauromo I, Koskenvuo M. Length of use and symptoms associated with premature removal of the levonorgestrel intrauterine system: a nation-wide study of 17,360 users. Br J Obstet Gynaecol 2000;107:335±339.

Rebecca French, Diana Mansour, Angela Robinson & John Guillebaud Department of Sexually Transmitted Diseases, Royal Free and University College Medical School, University College, London, UK PII: S0306 -5 456(00)00158 -3

Does histological incomplete excision of cervical intraepithelial neoplasia following large excision of transformation zone increase recurrence rates? A six year cytological follow up Sir, I read this article with interest and the authors are to be congratulated on their study. It clearly con®rms that women with incompletely excised CIN following large loop excision of the transformation zone are at higher risk of recurrence. As with so many useful observations, it often asks new questions. The ®rst of these concerns follow up. The authors conclude that long term colposcopic and cytological follow up are necessary. Why? The need for cytological follow-up is obvious, but what is the evidence that colposcopy would improve pick-up rates? There are no data provided to suggest that colposcopy would add anything and would justify the increased costs and service pressures that would ensue. Colposcopy is said to be compromised in previously treated patients. No evidence is presented in this study

772 CORRESPONDENCE

concerning the colposcopic features of those women who returned with abnormal smears. 75 (23%) of the women had incomplete excision. All women apparently underwent outpatient large loop excision of the transformation zone using standard treatment protocols. It would be of interest to know what the standard protocols were, with particular reference to the size of the loop used. For example, what proportion of the women had large loops used as opposed to medium-sized loops? Was the intention to excise completely the abnormality using excision alone or was a combination of excision and ablation performed? If so, was there any difference in outcome between these groups?

C. W. E. Redman Women and Childrens' Division, Department of Obstetrics and Gynaecology, City General, Stoke-on-Trent, UK PII: S03 06-5456(00)0015 9-5

Sir, We read the above mentioned study with interest. We agree with the authors' argument that recurrence of CIN is increased if the excision is incomplete. However, we disagree with the blanket statement that ªcytology and colposcopy should be used for follow up for every case of incomplete excisionº; and the available literature does not support this. Studies have been divided in their opinion as to the best method of follow up; ®rstly, because of the dif®culty in differentiating dysplastic acetowhite epithelium from immature squamous metaplasis at colposcopy. This gives high rates of false positive results leading to unnecessary cervical biopsy and its attendant morbidity 1. Secondly, reliance on cytology only for follow up has been shown to improve ef®ciency without placing any additional burden on the available resources 2. There is excellent data to suggest that incomplete excision in the presence of high grade disease or endocervical gland involvement is most likely to be associated with residual disease and increased recurrence 3,4. Intensive surveillance should, therefore, be directed to this group of women only.

References 1. Lopes A, Mor-Yosef S, Pearon St, et al. Is routine colposcopic assessment necessary following laser ablation of cervical intraepithelial neoplasis? Br J Obstet Gynaecol 1990;97:175±177. 2. Murdoch JB, Morgan PR, Lopes A, et al. Histological incomplete excision of cervical intraepithelial neoplasia after large loop excision of the transformation zone merits careful follow up, not treatment. Br J Obstet Gynaecol 1992;99:990±993. 3. Livasy CA, Maygarden SJ, Rajaratnam CT, Novotny DB. Predictors of recurrent dysplasis after a cervical loop electroautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement. Mod Pathol 1999;12(3):233±238. 4. Hulman G, Pickles CJ, Gie CA, et al. Frequency of cervical intraepithelial neoplasia following large loop excision of the transformation zone. J Clin Pathol 1998;51:375±377.

S. Das & K. A. J. Chin Department of Obstetrics and Gynaecology, Stafford General Hospital, Stafford, UK PII: S03 06-5456(00)0016 0-1

Sir, S. P. Dobbs and co-authors 1 are to be congratulated for having con®rmed that residual or recurrent cervical intra-epithelial neoplasia (CIN) when treated by large loop excision of the transformation zone is seen more frequently following histological incomplete excision. However, we are unsure how they conclude that colposcopic follow-up should be performed in this group of women. Their study was a retrospective review of women who were followed up by cytological assessment alone. No data were presented of women who were followed up by colposcopy and so no comment can be made concerning the advantages of this method of follow-up. Furthermore, to our knowledge, there is no conclusive evidence showing increased detection rates of residual or recurrent CIN by the use of colposcopy in this setting. In women whose CIN was incompletely excised at the endocervical margin (37 of 75 cases, 49%), it is hard to believe that a colposcopic examination might be of any value by itself or in addition to cytology. A discussion of the value of brush smears in this group of women, however, would have been of interest. If the authors believe there is value in performing colposcopic follow-up of these women, would this identify women with residual or recurrent CIN which is not detected cytologically; or does colposcopy identify recurrent CIN sooner than by cytological assessment alone? It is not possible from their study to establish whether CIN is missed by cytology alone. Furthermore, there is no evidence that earlier detection of CIN improves the outcome in this group of women. In their case series, two women developed invasive cancer of the cervix during the study period, both stage Ial, of which neither was identi®ed `incidentally'. Both cases were identi®ed cytologically, following which both women were referred for further investigation and diagnosis followed by simple hysterectomy. Both of these cases could have been adequately treated by loop cone biopsy were fertility an issue. A further twelve cases were seen to have residual or recurrent CIN (3 low-grade and 9 high-grade), all of whom were also detected cytologically and referred for further investigation, and treatment, presumably by large loop excision of the transformation zone. This paper, supports the value of cytological follow-up in these women, and provides no information on the value of colposcopy.

References 1. Dobbs SP, Asmussen T, Nunns D, Hollingworth J, Brown LJR, Ireland D. Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up. Br J Obstet Gynaecol 2000;107:1298±1301.

Raj Naik, Alberto de Barros Lopes & John Monaghan Northern Gynaeocological Oncology Centre, Queen Elizabeth Hospital, Gateshead, UK PII: S0 306-5456(00 )00 161-3

The relationship between increased folate stetabolism and the increased requirement for folate in pregnancy Sir, The article by Higgins et al. 1 presents de®nitive data that con®rms the previous ®ndings of this prestigious research group, that folate catabolites are increased in the third trimester of pregnancy. Their ®ndings make a signi®cant contribution to the scien-