1. 1016 BRITISH MEDICAL JOURNAL 24 APRIL 1976
protocol so that the collective experience of any increase in iodine intake must thus lead been 23 pregnancies reaching viability and
many institutions will contribute to the further to an initial increase in the frequency of reported spontaneously by doctors to Searle's
understanding and better management of such thyrotoxicosis, as was shown by the authors. -all from the United Kingdom. Nineteen
cases. Much more needs to be known if women If, however, iodine intake in the area becomes normal infants were reported and of the four
with renal transplants are to be carefully permanently adequate through iodine pro- cases of congenital abnormality one was that
selected to enjoy pregnancy and parenthood phylaxis the frequency of thyrotoxicosis would described by Miss P C Leighton and her
with maximum benefit to themselves and their eventually decrease. The increased incidence colleagues (24 April, p 949) with multiple
offspring. We doubt, however, if a decision to of thyrotoxicosis after iodine is added to food limb-reduction deformities. This is the only
undertake a transplant should ever be based on is thus a consequence of iodine deficiency. such case reported in Britain since the Gravi-
a desire for parenthood. An accumulation of thyrotoxicosis patients gard was first marketed in September 1972.
J M DAVISON in the generation in which iodine prophylaxis The size of the population at risk from which
T LIND is begun seems to be the price to pay for normal the case comes is unknown. (A very approxi-
MRC Reproduction and Growth Unit,
thyroid physiology in the following generations. mate indication may be obtained, based on the
Princess Mary Maternity Hospital When basal iodine intake is sufficient to fact that about 376 000 of these devices have
maintain normal hormonal balance occasional been sold within the British Isles.)
D N S KERR increases in iodine intake should not cause any In conclusion, I would agree with the last
Department of Medicine,
Royal Victoria Infirmary, increased frequency of thyrotoxicosis. In other paragraph of Dr Barrie's article. The likeli-
Newcastle upon Tyne words, bread and milk would still be preferable hood of spontaneous abortion, which may be
Davison, J M, Lind, T, and Uldall, P R, British3Journal to cakes and ale-albeit not for the goitrous. septic,2 and of other dangerous complications
of Obstetrics and Gynaecology. In press. of pregnancy and delivery3 is such that
1
2
Merkatz, J R, et al, Journal of the American Medical
Association, 1971, 216, 1749. PETER WAHLBERG most authorities would agree that "serious
Department of Internal Medicine, consideration should be given to terminating
Aland Central Hospital, pregnancies with a retained intrauterine
Mariehamn,
Hypoglycaemia in children undergoing Finland device" on maternal grounds. But on the
adenotonsillectomy figures given here the teratogenic risk to the
Becker, F 0, inYear Book of Endocrinology 1974, p 198. fetus if a Copper-7 device was in use would
Chicago, Year Book Medical Publishers, 1974.
SIR,-Those constantly concerned with not be added grounds for legal abortion.
eliminating the risks associated with operations
on the tonsils and adenoids will be grateful JOHN GUILLEBAUD
IUD and congenital malformation Nuffield Department of Obstetrics
to Dr C J H Kelnar for his contribution (27 and Gynaecology,
March, p 751). He states, however, "It is not SIR,-One must never dismiss reports of John Radcliffe Hospital,
unreasonable to suppose that some of the Oxford
possible iatrogenic damage to the developing
15 to 20 children who die each year after fetus. But the two cases described by Dr Snowden, R, FPA Medical Newsletter, No 59, 1976,
adenotonsillectomy die from the effects of Herbert Barrie (28 February, p 488) provide p 1.
unrecognised hypoglycaemia." It may well 2 Eisinger, S H, American J7ournal of Obstetrics and
little support for a cause-and-effect link Gynecology, 1976, 124, 393.
be that some children die from this cause, but between copper-containing intrauterine devices Vessey, M P, et al, Lancet, 1974, 1, 495.
the total number of deaths per annum is very Steven, J D, and Fraser, I S, Journal of Obstetrics and
(IUDs) and limb-reduction defects. As sug- Gynaecology of the British Commonwealth, 1974, 81,
much less than quoted. In the five years 1964-8 gested by Dr Robert Snowden (27 March, 282.
the annual number of deaths from this opera- p 770), conception and organogenesis in the
tion had dropped to little less than seven and second case may have occurred after expulsion
in 1970 figures from the Office of Population of the IUD. Moreover, the lead content Control of menstrual bleeding during
Censuses and Surveys showed that there (0-01-14,) of the Grafenberg ring in the first haemodialysis
was but one death and that from adenoid- case may have caused the malformation rather
ectomy without tonsillectomy. than the copper-if the association was not SIR,-Over the past two years a new intra-
In recent years improved management and a coincidental. The chief problem is that the uterine device (IUD) releasing progesterone
steady reduction in the number of operations relevant denominator is unknown-that is, the (Progestasert) has been used for contracep-
have combined to reduce the mortality rate to size of the population fitted with Grafenberg tion.'-' During these studies it was observed
very small proportions. Nevertheless, the rings and the number of in-situ pregnancies that total menstrual blood loss decreased and
utmost vigilance is still required, which should occurring. In Dr Snowden's study' these removals of the device for bleeding were
certainly take into account the important figures are available, and it is reassuring that no reduced.
factor publicised by Dr Kelnar. congenital abnormalities were reported among Patients with renal disease awaiting trans-
the 210) of 317 pregnancies reaching viability. plantation and undergoing haemodialysis often
STUART MAWSON What about devices which contain much experience heavy and troublesome menstrual
London Wl more (about 90 mg) of copper? The following periods. Control of these periods with con-
results are by courtesy of the medical depart- tinuous hormone therapy (usually a combined
ment of Searle Laboratories, High Wycombe, oestrogen and progestogen pill) often gives
Thyrotoxicosis induced by iodine in food and relate solely to the Copper-7 device rise to side effects. In an attempt to reduce
(Gravigard). In two international studies there these side effects we have used the progesterone
SIR,-I enjoyed reading the authoritative were 20 684 insertions, and 714 pregnancies IUD ior menstrual cycle control in four
paper by Drs J C Stewart and G I Vidor with Copper-7 devices in situ at conception patients awaiting renal transplantation. All
(14 February, p 372) in which they pointed have been reported. Of these, 167 reached four had chronic glomerulonephritis with
out that increased frequency of thyrotoxicosis viability, 800 were lost to follow-up, and the varying periods of amenorrhoea during the
was observed after addition of iodine to the remainder were ectopic or ended in spontane- progression of their kidney disease. With
diet in northern Tasmania. It has been ous or induced abortion. Normal babies dialysis all developed heavy periods requiring
suggested' that the development of endemic resulted from 159 pregnancies. No details were treatment. Norethisterone 30 mg/day con-
goitre is related to a balance between thyroid- given about three infants and the remaining trolled two patients' bleeding but gave other
stimulating hormone (TSH) production and five had the following malformations: (1) per- unpleasant side effects, such as a bloated
thyroid size. Iodine deficiency thus leads to manent bald spot; (2) bilateral congenital feeling and water retention. On reduction of
decreased thyroid hormone production, which eyelid ptosis; (3) fatty tumour on the back; the dose to 10 mg/day both experienced
in turn causes increased TSH secretion and (4) congenital dislocation of hip (breech troublesome breakthrough bleeding. Of the
increased thyroid size until there is enough delivery); (5) lumbosacral meningomyelocele other two patients, one had heavy periods
thyroid tissue to trap a proportion of circulat- and bilateral talipes-neonatal death at seven with norethisterone and the other severe
ing iodine large enough to maintain normal days. If the three doubtful cases are included breakthrough bleeding. All four patients
hormone levels. Any increase in iodine intake the incidence of congenital defects was eight experienced troublesome menstrual side effects
in such persons thus causes a trend towards out of 167 or 4-80o (very close to the figure when combined oral contraceptive prepara-
thyrotoxicosis because the thyroid is adjusted quoted by Dr Barrie as the expected rate). tions were used.
to a higher than normal degree of iodine Note that no limb-reduction defects were The progesterone IUD was easily inserted
utilisation. reported. However, in addition to the above in all four patients. Following insertion all
In a goitre region with iodine deficiency cases from a defined population there have four had regular menstrual cycles with accept-

2. BRITISH MEDICAL JOURNAL 24 APRIL 1976 1017
able amounts of blood loss. The total length of and also emphasise the importance of checking ference of such treatment with the contracep-
menstrual bleeding and the amount (number the position of the IUD in patients presenting tive effect of the device should be borne in
of tampons used) was reduced in all cases. with low abdominal pain who have had one of mind.
One patient noted some intermenstrual these devices fitted.
spotting, but this was acceptable. DEREK J PEARCE B ASTEDT
The first two patients have been followed West Kent General Hospital, P LIEDHOLM
up for 11 and 16 months respectively and are Maidstone
Department of Obstetrics and
alive and well, still with regular menstrual Steptoe, P C, Laparascopy in Gynaecology, 2nd edn.
Gynaecology,
cycles and acceptable blood loss. The third University of Lund,
Edinburgh, Livingstone, 1975. Allmfinna Sjukhuset,
patient was followed up for seven months and Malmo, Sweden
during this time had regular cycles with no
side effects; four months after insertion she Liedholm, P, and Astedt, B, International Journal of
Fertility, 1975, 20, 24.
had a kidney transplant and three months later 2
Ingemanson-Nordqvist, B, and Killen, B, Experi-
died from a massive gastrointestinal haemor- IUDs and fibrinolysis mnertal Cell Research, 1961, 21, 232.
'Larsson, B, Liedholm, P, and Astedt, B, International
rhage. The fourth patient was seen for nine Journal of Fertility, 1975, 20, 77.
months after IUD insertion; after five months SIR,-In your leading article (7 February, 4Astedt, B, Pandolfi, M, and Nilsson, I M, Proceedings
p 304) you suggest that the mechanism of the of the Society for Experimental Biology and Medicine,
she also had a kidney transplant and four 1972, 139, 1421.
months later died from pneumococcal pneu- tendency of intrauterine contraceptive devices
monia. These two deaths were not related to (IUDs) to cause heavy periods might not be
the IUD use. completely separable from the mechanism of Supervision of repeat prescribing
We conclude from this small series that the the device's contraceptive action.
progesterone IUD offers definite advantages We examined fertilised rat ova histochemic- SIR,-As director of the research centre from
for patients undergoing haemodialysis who ally for their fibrinolytic activity.' Activity which the paper by Mrs S M Shaw and Mr
have heavy periods. In contrast to the use of was found during tubal passage but disappeared L J Opit comes I am naturally distressed at the
systemic steroids intrauterine progesterone at implantation. Simultaneously the fibrino- astonishment, hilarity, and anger of the
produces regular cycles with acceptable lytic activity of the endometrium disappeared. practitioners involved (20 March, p 713). The
menstrual blood loss. It is well known that inhibition of fibrinolysis authors themselves are, of course, responsible
J NEWTON in organ and cell culture on clotted substrates for the views expressed in the paper and I
S A SNOWDEN promotes adhesion and growth.2 Absence of would not wish to speak for them, but I think
VICTOR PARSONS fibrinolytic activity might thus be a pre- I must in fairness reply on behalf of a number
Department of Obstetrics and requisite for implantation of the zygote. In of other loyal and hardworking collaborators
Gynaecology, the light of these observations it is of interest and say how much I regret unwarranted public
King's College Hospital Medical School, to note that IUDs raise the fibrinolytic activity
London SE5 castigation of their work.
in the endometrium, which, in contrast to I appreciate that these comments arise from
Pharriss, B B, et al, Fertility and Sterility, 1974, 25, that of non-users, is localised to the superficial the hot sense of injustice which the partners
915. cell layer.3
2Martinez-Manatou, J, et at, Fertility and Sterility, feel, and this partly from their failure to receive
1974, 25, 922. The disappearance of endometrial fibrino- their transcript of the paper. We suppose this
'Rosado, A, et al, Contraception, 1974, 9, 39. lytic activity at the time of decidualisation error must have occurred in this office and
prompted us to study the human decidua in must accept responsibility, although we are
tissue culture for inhibitors of fibrinolysis. now unable to trace events because of a
Laparoscopic removal of IUDs from the We used a method in which tissue explants burglary with much destruction and sub-
abdomen are cultured in the presence of, but not in sequent disorganisation. Absence of acknow-
contact with, a preformed standard ledgements in the paper was due to the part-
SIR,-Perforation of the uterine wall by intra- plasminogen-contaminated fibrin clot. Uro- ners' request for non-identification following
uterine contraceptive devices (IUDs) is an kinase added to the culture medium degrades their perusal and commentary upon earlier
uncommon but not rare occurrence. With the the fibrin with consequent accumulation of accounts of the work and not to any intended
increasing popularity of the IUD the incidence stable fibrin degradation products (FDP) in slight.
of this complication will quite possibly increase. the medium. The amount of FDP is assessed There is one other point I must put straight.
We have recently seen two such cases. Both pre- immunochemically. When inhibitors are re- It is possible to read one of the sentences in
sented with diffuse acute low abdominal pain which leased from the cultured explants they will the partners' letter to imply that Mrs Shaw
had started three or four days after insertion of an inhibit the formation of FDP.4 The results are changed the treatment of one of the patients.
IUD (Lippes loop, size C, in one and Copper-7 given in the table. This was raised in discussion between our-
(Gravigard) in the other) by an experienced general selves and the practice, when I was present,
practitioner. The pain had gradually become more Inhibition of urokinase by decidua in organ culture. and it was explained that a locum doctor
severe over five or six days until admission. Both Mean value of two cultures. Each value denotes FDP changed the treatment when informed of the
patients were multiparous and apparently had content in pkg/l of Parker medium
normal pelvic anatomy at insertion of the IUD. situation. This was not doubted by the
On examination there was generalised lower Days of culture partners at the time and I hope they are not
abdominal tenderness and marked cervical excita- doubting it now. Perhaps I am over-sensitive
tion. The thread of the IUD could be neither seen 1 2 3 in treating a bit of ambiguous English as
nor felt in the cervix. Urokinase 3 0 U ml alone 153 228 448 something which could be seen as an innuendo.
Removal was by laparoscope, using a method Urokinase 3.0 U'ml decidua 15 69 120
Urokinase 1-5 U,ml
basically similar to that described by Steptoe,' Urokinase 1-5 U'ml alone 27 87 195
under general anaesthesia. The thread attached to Urokinase 075 U ml -ralone
decidua 7 22 38 E G KNOX
1 5 15 60
the IUD was in both cases visualised by manipula- Urokinase 0 75 U,ml -+ decidua 0 0 5 Health Services Research Centre,
Department of Social Medicine,
tion of the uterus by means of Hulka forceps in the Decidua alone .I__ .. . _ 1-5 University of Birrningham
cervix. The thread was then grasped with Palmer
forceps passed into the abdomen through a trocar
inserted at the junction of the medial third and the We also examined decidua cultures for their
lateral two-thirds of a line joining the umbilicus influence on the fibrinolytic activity of rat ova. Disposable bacteriological loops and
and right anterior superior iliac spine. The forceps When rat ova were incubated on fibrin slides vaginal discharge
and trocar were then withdrawn together, and the without culture medium or with addition of
IUD, still grasped by its thread with the forceps, fresh medium the mean lytic area was found
SIR,-The investigation of a vaginal discharge
was manipulated through the tiny incision made by to be 90 x 103 tiM2. On the slides to which
involves sample taking from the urethra,
insertion of the trocar. In both cases the site on the human or rat decidua culture medium had
cervix, and vagina for Gram staining, culture,
posterior aspect of the uterus at which perforation
had occurred was scarcely noticeable. The only been added to the fibrin film the lytic areaand wet-film microscopy. The standard
other pathological finding in the abdomen was a never exceeded the area of the ovum-that is,
bacteriological swab has certain drawbacks.
pool of "old" blood, about 20-30 ml in volume, in <18 x 103 jiM2. It is too big to enter the urethra without pain
the pouch of Douglas. In both cases the patient was IUDs medicated with inhibitors of fibrino-
and may be too big to enter the cervical canal.
able to be discharged the following day. Any Gram films made may be obscured by
lysis have been claimed to decrease the inci-
These cases illustrate the use of laparoscopy dence of intermenstrual bleeding as well as
carbon particles if a charcoal-coated swab is
as a therapeutic as well as diagnostic process heavy periods. However, the possible inter- used. A common alternative is the platinum