/. biosoc. Sci. (1975) 7, 367-375
RECENT STUDIES IN INTRAUTERINE DEVICES: A REAPPRAISAL* ROBERT SNOWDEN Family Planning Research Unit, University of Exeter (Received \6th December 1974)
Introduction
Since the first rush of publications on IUDs following the start of Tietze's Cooperative Statistical Programme for the Evaluation of IUDs (Tietze & Lewit, 1970) there has rarely been a period in which a report relating to newer, 'secondgeneration' devices has not been published. There are degrees of sophistication in these reports varying from the odd anecdotal reference and highly subjective clinical impression to carefully constructed and evaluated large-scale clinical and field trials. This in itself creates problems, for the carefully constructed trials tend to be reported long after the clinical impressions have been publicized. In some cases the impressionistic information has so affected opinion that the presentation of data from large-scale trials providing greater validity and reliability becomes merely an academic exercise. The most recent example of this was the widespread publicity over the Dalkon Shield in the United States—a situation which is now described as the 'Dalkon Shield affair: a bad lesson in science and decision-making' (Culliton & Knopman 1974). It is easy to argue that 'bad lessons' have their uses, but these uses, by definition, can only be seen after the event. The precipitous action in relation to the withdrawal of the Dalkon Shield was based on a report describing the experience of one doctor and his colleagues. This decision left millions of women throughout the world in a state of uncertainty, and increased the mortality risk many times over in those cases where the device was actually removed. Those attending the public hearings about this Dalkon Shield 'affair' were repeatedly informed of the greater dangers associated with the use of oral contraceptives and even of pregnancy itself. Any review of recent developments in IUDs must then take account of the type of information being offered. This can be at three levels depending on whether * Based on a paper read at the Symposium on Current Fertility Control, Charing Cross Hospital, November 1974. 367
368
Robert Snowden
it relates to general field trials, more specific clinical trials or mere conjecture at any given time. Most papers concerned with IUD development tend to concentrate on the 'exciting' prospects ahead, that is, on the newer devices which have limited clinical data to support the opinions given. It is not suggested that the newer devices should be ignored—no review of recent developments could be complete without them—but rather that they should be seen in perspective. There are still lessons to be learned from an analysis of the early data relating to IUDs and evidence will be presented here relating to each level of information.
Data collection The Family Planning Research Unit (FPRU) in the University of Exeter has been systematically collecting data relating to IUDs on a country-wide basis since April 1972, and in relation to Exeter and the South West of England since 1964 (FPRU, 1974f). The Unit receives both admission and follow-up data relating to IUD fittings undertaken at twenty centres situated in various parts of the United Kingdom. At the present time, over 100,000 records are held at the Unit relating to almost 25,000 IUD fittings. A systematic procedure for data collection and analysis has been established (FPRU, 1972) and—of even greater importance—the work is undertaken independently of the manufacturers/distributors of the devices examined. The internal organization of the Unit is modestly financed by the Medical Research Council but those collaborating in the IUD Research Network receive no fee for their work. It is believed that, by mutual effort, a worthwhile and informed dialogue concerning the development of IUDs has been established.
Results of general field trials In recent years, a number of devices have been made available for use in general field trials; Table 1 gives the results of some of these trials. These figures contain nothing that is startlingly newAThe drop in the expulsion rate was predicted when the bio-engineer became interested in the development of a 'non-expellable' device. The M device is noticeable in this regard and closely reflects the aims and success of the MIT team under Lardner (Lardner et al., 1970) and of the inventors of the device (Chaft, Silberman & Stone, 1969). The interesting point about these figures is the similarity in the pregnancy rates reported. With one exception (the smallest size Lippes Loop, but with only a small number of fittings) they all fall within the narrow range of 2-4-3-6 per 100 users. If the Lippes IVB is removed, the range is narrowed to 0-5 per 100 users which means that the range in the pregnancy rate between the two largest sizes of Lippes Loop, the M213, the Dalkon Shield and the Gravigard device is one pregnancy in every 200 women at the end of 1 year of use. The lesson to be drawn
Recent studies in IUDs
369
Table 1. Net cumulative rates for selected events to 12 ordinal months of use per 100 users of IUDs in the UK
IUD
Lippes Loop IA* (smallest) Lippes Loop IVB* Lippes Loop IIIC* Lippes Loop IID* (largest) M213* Dalkon Shieldf GravigardJ
Pregnancy
Expulsion
Bleeding/pain removal
4-4 (2-1) 3-6 (0-8) 2-8 (0-6) 2-4 (0-6) 2-9 (0-6) 2-8 (0-3) 2-8 (0-5)
15-6(3-9) 12-2 (1-4) 10-4(1-2) 5-9 (1-0) 0-6 (0-3) 2-0 (0-3) 7-2 (0-7)
4-7 (2-2) 5-9 (10) 7-1 (1-0) 8-1 (1-1) 7-4 (0-9) 4-2 (0-4) 51 (0-6)
No. of fittings 114 702 810 739
1021 4191 2002
Sources: * Snowden (1971). Rates for the South West of England only; rates not yet available from National IUD Project. fFPRU (1974a). JFPRU (1974b). SE in parentheses.
from this is that despite the talk about the larger surface area, the addition of copper wire to the surface of the device and the non-expellable device all reducing the pregnancy rate, the difference between the early devices and their successors is hardly measurable. This is a lesson worth noting and without the large-scale collection of data which provide the evidence, the lesson would not have been learned. Another interesting point is the relationship between the pregnancy and bleeding/pain removal rates given in Table 1. Although not complete, there appears to be an inverse relationship between these two rates. As the pregnancy rate decreases, the bleeding/pain removal rate increases; this is most obvious for the four sizes of Lippes Loop. There is also a direct relationship between the pregnancy and expulsion rates; as the pregnancy rate rises, the expulsion rate also rises. Findings such as these prompted the pursuit of the 'non-expellable' device. It was mistakenly believed that by reducing the expulsion rate, the pregnancy rate would also fall but this has not been supported by evidence. There must be an intervening variable here which affects both the likelihood of pregnancy and expulsion of the device from the uterus. A third lesson which has been learned and publicized by the Unit is that the interpretation of effectiveness rates, in some respects, is a serious problem. At best they represent a compromise in the rates obtained from a number of centres— rates which can vary very greatly—and at worst they represent a process of statistical averaging-out which has little or no relationship to what happens in reality. This is not the place to argue for or against the use of means, medians or modes but one thing is clear—the same device fitted by different teams among differing 26
370
Robert Snowden
groups of acceptors has different records of success or failure. For example, some figures obtained in the recent field trial of the Dalkon Shield clearly show the variation in these event rates but this does not invalidate the collection of data from more than one centre (FPRU, 1974a). On the contrary, it remains preferable to do so. By using the same procedures in the recording and analysis of large amounts of data from differing centres it has been possible to reveal this problem of variation in the event rate associated with the use of a particular IUD model. Table 2. Selected net cumulative event rates at 12 ordinal months of use per 100 users of Dalkon Shield
Centre
Pregnancy
Expulsion
Bleeding/pain removal
Loss to follow-up
A B C D E F G H
1-5 (0-7) 6-8 (2-9) 1-7(0-3) 3-4(1-1) 5-1 (1-9) 7-0 (2-6) 5-1 (1-1) 5-1(1-9)
3-4(1-0) 3-6 (2-1) 0-8 (0-2) 2-8 (1-0) 2-2 (1-2) 9 0 (2-9) 3-7 (0-9) 1-9(1-2)
0-9 (0-5) 12-7 (4-0) 2-2 (0-4) 2-3 (0-9) 7-3 (2-3) 7-9 (2-8) 11-3(1-6) 15-8 (3-4)
15-1 (20) 7-2 (3-1) 5-9 (0-6) 3-8(1-2) 27-0 (4-2) 30-4 (5-2) 0 0 (00) 8-1 (2-4)
All centres
2-8 (0-3)
2 0 (0-3)
4-2 (0-4)
8-1 (0-5)
Source: FPRU (1974a) Table IX, p. 13, and additional data (not published) relating to the Glasgow and London centres. SE in parentheses.
If nothing else, it is a warning that merely fitting the 'right' device in what is believed to be the 'right' place is not enough. The interplay between the IUD model, the person fitting the device and the person receiving it was little considered until explanations were needed to account for these differential success rates. The pursuit of the 'zero' pregnancy rate, like the pursuit of the non-expellable device, may be based on a misunderstanding. The only way to produce a device that is 'pregnancy-proof is to produce one that is also 'doctor- or fitter-proof as well as 'user-proof. More profitable perhaps is the approach which looks principally at the side effects of IUD use in relation to the models which already exist. Table 1 shows that the problem of bleeding and/or pain is a far more serious hurdle than the rate of unwanted pregnancy to the acceptability of the IUD as a fertility regulating method. Before adding yet more surface area and yet more copper to second- and third-generation IUD models perhaps those already in use ought to be more closely examined. Detailed reports of the field trials of the Dalkon Shield
Recent studies in IUDs
371
(FPRU, 1974a) and the Gravigard device (FPRU, 1974b) have already been published, so those findings will not be repeated here. The purpose in presenting the foregoing is to suggest that a careful look at what is already known could be a far more profitable exercise than the hasty development of new devices. The fitting of specific IUD models appears to be subject to frequent changes in fashion but the subject of fertility regulating behaviour in general, and the fitting of IUDs in particular, is too serious a subject to be treated in this way. In relation to this, the new ML combined multiload contraceptive Cu-200 is an example. This device, which combines the characteristics of the Dalkon Shield and the Copper T device, is illustrated in Text-fig. 1. At the recent World Conference on Fertility and Sterility (November 1974) 31 papers were presented relating to intrauterine contraception; among these, fourteen devices were discussed (Goldsmith, personal communication).
Text-fig. 1. The ML combined multiload contraceptive Cu-200.
Results of clinical trials A small number of more carefully controlled clinical trials have been undertaken by the Unit. Some of the devices examined are also included in field trials but other devices are in an earlier phase of development. The data on which these clinical trials are based are still of sufficient quantity and quality to permit detailed analysis but constraints as to the specificity of the population selected for the trial do exist. Those taking part in a clinical trial are often more carefully chosen than those taking part in a field trial. The need for a more rigorous follow-up after fitting the device and the closer scrutiny involved in a clinical trial introduce biases that are not so obvious in the field trial. Nevertheless this earlier phase in the assessment of an IUD is of great importance and is often the determining factor in deciding whether or not a field trial should, in fact, take place.
372
Robert Snowden
Dalkon Shield: copper versus non-copper This small-scale study (FPRU, 1974e) undertaken at four centres revealed that the inclusion of copper dust and copper sulphate in the composition of the Dalkon Shield had little or no effect on the event rate associated with pregnancy, expulsion of the device from the uterus or removal of the device following a complaint of bleeding and/or pain (Table 3). The addition of copper to the polyethylene 'mix' of the Dalkon Shield occurred at the time when the effect of copper in the uterus was being demonstrated in certain Chilean studies. It is of interest that it was copper that was added for the declared purpose of providing radio-opacity to this device. Table 3. Selected net cumulative event rates at 12 ordinal months of use per 100 users of the Dalkon Shield containing, or without, copper
Dalkon Shield With copper Without copper
Pregnancy
Expulsion
Bleeding/pain removal
No. of fittings
1-2(0-9) 0-7(0-7)
2-5(1-3) 2-5(1-3)
3-5(1-5) 6-6(2-1)
178 177
Source: FPRU (1974e) Tables II and HI, pp. 8 and 9. SE in parentheses.
Dalkon Shield and the unsuccessful use of other IUDs This single centre study was aimed at studying the retention capabilities of the Dalkon Shield among women who had experience of unsuccessful use of other IUDs (FPRU, 1974e). The results suggest that there is some justification for the claim that this device has a low expulsion rate (Table 4). Table 4. Previous unsuccessful use of an IUD; selected net cumulative event rates at 12 ordinal months of use per 100 users
Dalkon Shield (normal population) Dalkon Shield (previous unsuccessful IUD use)
Pregnancy
Expulsion
Bleeding/pain removal
No. of fittings
2-8 (0-3)
2-3 (0-3)
8-1 (0-5)
4191
4-3 (2-1)
3-3 (1-8)
5-4 (2-3)
98
Source: FPRU (1974e) Table 4, p. 18. SE in parentheses.
Recent studies in IUDs
373
Comparison of winged and F Antigon devices This double blind comparative trial at ten centres produced some interesting results (Table 5) but difficulty was encountered in the fitting of the device (both models) in a large number of cases. By including a flexible membrane in the centre of the device the F model provides a greater area of contact with the endometrium without increasing the overall size of the device. The future of this device is still not clear but those who look first to the pregnancy rate can find some encouragement here. Table 5. Comparison of two models of the Antigon device; selected net cumulative event rates at 12 months of use per 100 users Antigen device Winged model F model
Pregnancy
Expulsion
1-1 (0-8) 0-5 (0-5)
6-5 (1-8) 5-2(1-6)
Bleeding/pain removal
No. of fittings
8-5 (2-1) 10-4 (2-3)
201 209
Source: Data held at the FPRU; report in press. SE in parentheses. New devices with little or no UK evidence from independent trials
The FPRU has been asked to look at a number of devices, some of which have been assessed by referee teams in various parts of the UK. (1) The Latex Leaf device (Text-fig. 2) has been assessed and rejected in its present form; the thread tended to tear through the device on removal and fears were expressed concerning the use of latex rubber in the uterus. Further laboratory evidence has been requested (FPRU, 1973). (2) The LEM device (Text-fig. 3) has been assessed and rejected (FPRU, 1974c). (3) The Copper Omega (Text-fig. 4) has been assessed and encouragement for further clinical trials has been offered to the inventor (FPRU, 1974d). Other devices have been produced but independent assessment in the UK has yet to be undertaken on any scale. There are also other devices used in other parts of the world, such as the Weiss device, the Techna Fluid Filled IUD, the Pleated Membrane, the Alza T, and Provera 7; the list could be extensive. By providing a backward look to the early 1960s when it was claimed by some that the IUD would solve the world population crisis (Guttmacher, 1965; Lloyd, 1965) some lessons can be learned. Perhaps the most important one is that new technology may not be the hoped for answer in the search for an IUD with a zero pregnancy rate. A careful examination of what is already known might be more useful.
374
Robert Snowden
Text-fig. 2. The Latex Leaf intrauterine device.
Copper wire 2001 mm2
Device in fundus of uterus
Head of device
Nylon threads
Text-fig. 3. The LEM intrauterine device. Text-fig. 4. The Copper Omega intrauterine device.
Recent studies in IUDs
375
References M.E., SILBERMAN, E. & STONE, M. (1969) The M, a new intrauterine contraceptive device. Am. J. Obstet. Gynec. 105, 279. CULLITON, B. & KNOPMAN, D. (1974) Dalkon Shield affair: a bad lesson in science and decisionmaking. Science, N. Y. 185,839. FPRU (1972) Description of Unit and National IUD Network. Report No. 1, Family Planning Research Unit, University of Exeter. FPRU (1973) Preliminary Assessment of the Latex Leaf. Report No. 5, Family Planning Research Unit, University of Exeter. FPRU (1974a) United Kingdom Field Trial of the Dalkon Shield. Report No. 7, Family Planning Research Unit, University of Exeter. FPRU (1974b) United Kingdom Field Trial of the Gravigard Device. Report No. 8, Family Planning Research Unit, University of Exeter. FPRU (1974c) Preliminary Assessment of the LEM Intrauterine Device. Report No. 9, Family Planning Research Unit, University of Exeter. FPRU (1974d) Preliminary Assessment of the Copper Omega Intrauterine Device. Report No. 10, Family Planning Research Unit, University of Exeter. FPRU (1974e) Two Dalkon Shield Studies. Report No. 12, Family Planning Research Unit, University of Exeter. FPRU (1974f) Progress Report April \912~June 1974. Report No. 14, Family Planning Research Unit, University of Exeter. GUTTMACHER, A.F. (1965) Intra-uterine contraceptive devices. /. Reprod. Fert. 10, 115. LARDNER, T., SHACK, W., TAM, P., BELSKY, R. & SCHUBECK, F. (1970) IUD Information Handbook. The Pathfinder Fund, Boston, USA. LLOYD, R. (1965) Proposal for a World Family Plan. Int. Dev. Rev. 7, 4. SNOWDEN, R. (1971) Social Factors in the Use and Effectiveness of the Intrauterine Device. Ph.D. thesis, University of Exeter. TIETZE, C. & LEWIT, S. (1970) Evaluation of intrauterine devices: ninth progress report of the Cooperative Statistical Program. Stud. Fam. Plann. No. 55, 1. CHAFT,
RECENT STUDIES IN INTRAUTERINE DEVICES: A REAPPRAISAL* ROBERT SNOWDEN Family Planning Research Unit, University of Exeter (Received \6th December 1974)
Introduction
Since the first rush of publications on IUDs following the start of Tietze's Cooperative Statistical Programme for the Evaluation of IUDs (Tietze & Lewit, 1970) there has rarely been a period in which a report relating to newer, 'secondgeneration' devices has not been published. There are degrees of sophistication in these reports varying from the odd anecdotal reference and highly subjective clinical impression to carefully constructed and evaluated large-scale clinical and field trials. This in itself creates problems, for the carefully constructed trials tend to be reported long after the clinical impressions have been publicized. In some cases the impressionistic information has so affected opinion that the presentation of data from large-scale trials providing greater validity and reliability becomes merely an academic exercise. The most recent example of this was the widespread publicity over the Dalkon Shield in the United States—a situation which is now described as the 'Dalkon Shield affair: a bad lesson in science and decision-making' (Culliton & Knopman 1974). It is easy to argue that 'bad lessons' have their uses, but these uses, by definition, can only be seen after the event. The precipitous action in relation to the withdrawal of the Dalkon Shield was based on a report describing the experience of one doctor and his colleagues. This decision left millions of women throughout the world in a state of uncertainty, and increased the mortality risk many times over in those cases where the device was actually removed. Those attending the public hearings about this Dalkon Shield 'affair' were repeatedly informed of the greater dangers associated with the use of oral contraceptives and even of pregnancy itself. Any review of recent developments in IUDs must then take account of the type of information being offered. This can be at three levels depending on whether * Based on a paper read at the Symposium on Current Fertility Control, Charing Cross Hospital, November 1974. 367
368
Robert Snowden
it relates to general field trials, more specific clinical trials or mere conjecture at any given time. Most papers concerned with IUD development tend to concentrate on the 'exciting' prospects ahead, that is, on the newer devices which have limited clinical data to support the opinions given. It is not suggested that the newer devices should be ignored—no review of recent developments could be complete without them—but rather that they should be seen in perspective. There are still lessons to be learned from an analysis of the early data relating to IUDs and evidence will be presented here relating to each level of information.
Data collection The Family Planning Research Unit (FPRU) in the University of Exeter has been systematically collecting data relating to IUDs on a country-wide basis since April 1972, and in relation to Exeter and the South West of England since 1964 (FPRU, 1974f). The Unit receives both admission and follow-up data relating to IUD fittings undertaken at twenty centres situated in various parts of the United Kingdom. At the present time, over 100,000 records are held at the Unit relating to almost 25,000 IUD fittings. A systematic procedure for data collection and analysis has been established (FPRU, 1972) and—of even greater importance—the work is undertaken independently of the manufacturers/distributors of the devices examined. The internal organization of the Unit is modestly financed by the Medical Research Council but those collaborating in the IUD Research Network receive no fee for their work. It is believed that, by mutual effort, a worthwhile and informed dialogue concerning the development of IUDs has been established.
Results of general field trials In recent years, a number of devices have been made available for use in general field trials; Table 1 gives the results of some of these trials. These figures contain nothing that is startlingly newAThe drop in the expulsion rate was predicted when the bio-engineer became interested in the development of a 'non-expellable' device. The M device is noticeable in this regard and closely reflects the aims and success of the MIT team under Lardner (Lardner et al., 1970) and of the inventors of the device (Chaft, Silberman & Stone, 1969). The interesting point about these figures is the similarity in the pregnancy rates reported. With one exception (the smallest size Lippes Loop, but with only a small number of fittings) they all fall within the narrow range of 2-4-3-6 per 100 users. If the Lippes IVB is removed, the range is narrowed to 0-5 per 100 users which means that the range in the pregnancy rate between the two largest sizes of Lippes Loop, the M213, the Dalkon Shield and the Gravigard device is one pregnancy in every 200 women at the end of 1 year of use. The lesson to be drawn
Recent studies in IUDs
369
Table 1. Net cumulative rates for selected events to 12 ordinal months of use per 100 users of IUDs in the UK
IUD
Lippes Loop IA* (smallest) Lippes Loop IVB* Lippes Loop IIIC* Lippes Loop IID* (largest) M213* Dalkon Shieldf GravigardJ
Pregnancy
Expulsion
Bleeding/pain removal
4-4 (2-1) 3-6 (0-8) 2-8 (0-6) 2-4 (0-6) 2-9 (0-6) 2-8 (0-3) 2-8 (0-5)
15-6(3-9) 12-2 (1-4) 10-4(1-2) 5-9 (1-0) 0-6 (0-3) 2-0 (0-3) 7-2 (0-7)
4-7 (2-2) 5-9 (10) 7-1 (1-0) 8-1 (1-1) 7-4 (0-9) 4-2 (0-4) 51 (0-6)
No. of fittings 114 702 810 739
1021 4191 2002
Sources: * Snowden (1971). Rates for the South West of England only; rates not yet available from National IUD Project. fFPRU (1974a). JFPRU (1974b). SE in parentheses.
from this is that despite the talk about the larger surface area, the addition of copper wire to the surface of the device and the non-expellable device all reducing the pregnancy rate, the difference between the early devices and their successors is hardly measurable. This is a lesson worth noting and without the large-scale collection of data which provide the evidence, the lesson would not have been learned. Another interesting point is the relationship between the pregnancy and bleeding/pain removal rates given in Table 1. Although not complete, there appears to be an inverse relationship between these two rates. As the pregnancy rate decreases, the bleeding/pain removal rate increases; this is most obvious for the four sizes of Lippes Loop. There is also a direct relationship between the pregnancy and expulsion rates; as the pregnancy rate rises, the expulsion rate also rises. Findings such as these prompted the pursuit of the 'non-expellable' device. It was mistakenly believed that by reducing the expulsion rate, the pregnancy rate would also fall but this has not been supported by evidence. There must be an intervening variable here which affects both the likelihood of pregnancy and expulsion of the device from the uterus. A third lesson which has been learned and publicized by the Unit is that the interpretation of effectiveness rates, in some respects, is a serious problem. At best they represent a compromise in the rates obtained from a number of centres— rates which can vary very greatly—and at worst they represent a process of statistical averaging-out which has little or no relationship to what happens in reality. This is not the place to argue for or against the use of means, medians or modes but one thing is clear—the same device fitted by different teams among differing 26
370
Robert Snowden
groups of acceptors has different records of success or failure. For example, some figures obtained in the recent field trial of the Dalkon Shield clearly show the variation in these event rates but this does not invalidate the collection of data from more than one centre (FPRU, 1974a). On the contrary, it remains preferable to do so. By using the same procedures in the recording and analysis of large amounts of data from differing centres it has been possible to reveal this problem of variation in the event rate associated with the use of a particular IUD model. Table 2. Selected net cumulative event rates at 12 ordinal months of use per 100 users of Dalkon Shield
Centre
Pregnancy
Expulsion
Bleeding/pain removal
Loss to follow-up
A B C D E F G H
1-5 (0-7) 6-8 (2-9) 1-7(0-3) 3-4(1-1) 5-1 (1-9) 7-0 (2-6) 5-1 (1-1) 5-1(1-9)
3-4(1-0) 3-6 (2-1) 0-8 (0-2) 2-8 (1-0) 2-2 (1-2) 9 0 (2-9) 3-7 (0-9) 1-9(1-2)
0-9 (0-5) 12-7 (4-0) 2-2 (0-4) 2-3 (0-9) 7-3 (2-3) 7-9 (2-8) 11-3(1-6) 15-8 (3-4)
15-1 (20) 7-2 (3-1) 5-9 (0-6) 3-8(1-2) 27-0 (4-2) 30-4 (5-2) 0 0 (00) 8-1 (2-4)
All centres
2-8 (0-3)
2 0 (0-3)
4-2 (0-4)
8-1 (0-5)
Source: FPRU (1974a) Table IX, p. 13, and additional data (not published) relating to the Glasgow and London centres. SE in parentheses.
If nothing else, it is a warning that merely fitting the 'right' device in what is believed to be the 'right' place is not enough. The interplay between the IUD model, the person fitting the device and the person receiving it was little considered until explanations were needed to account for these differential success rates. The pursuit of the 'zero' pregnancy rate, like the pursuit of the non-expellable device, may be based on a misunderstanding. The only way to produce a device that is 'pregnancy-proof is to produce one that is also 'doctor- or fitter-proof as well as 'user-proof. More profitable perhaps is the approach which looks principally at the side effects of IUD use in relation to the models which already exist. Table 1 shows that the problem of bleeding and/or pain is a far more serious hurdle than the rate of unwanted pregnancy to the acceptability of the IUD as a fertility regulating method. Before adding yet more surface area and yet more copper to second- and third-generation IUD models perhaps those already in use ought to be more closely examined. Detailed reports of the field trials of the Dalkon Shield
Recent studies in IUDs
371
(FPRU, 1974a) and the Gravigard device (FPRU, 1974b) have already been published, so those findings will not be repeated here. The purpose in presenting the foregoing is to suggest that a careful look at what is already known could be a far more profitable exercise than the hasty development of new devices. The fitting of specific IUD models appears to be subject to frequent changes in fashion but the subject of fertility regulating behaviour in general, and the fitting of IUDs in particular, is too serious a subject to be treated in this way. In relation to this, the new ML combined multiload contraceptive Cu-200 is an example. This device, which combines the characteristics of the Dalkon Shield and the Copper T device, is illustrated in Text-fig. 1. At the recent World Conference on Fertility and Sterility (November 1974) 31 papers were presented relating to intrauterine contraception; among these, fourteen devices were discussed (Goldsmith, personal communication).
Text-fig. 1. The ML combined multiload contraceptive Cu-200.
Results of clinical trials A small number of more carefully controlled clinical trials have been undertaken by the Unit. Some of the devices examined are also included in field trials but other devices are in an earlier phase of development. The data on which these clinical trials are based are still of sufficient quantity and quality to permit detailed analysis but constraints as to the specificity of the population selected for the trial do exist. Those taking part in a clinical trial are often more carefully chosen than those taking part in a field trial. The need for a more rigorous follow-up after fitting the device and the closer scrutiny involved in a clinical trial introduce biases that are not so obvious in the field trial. Nevertheless this earlier phase in the assessment of an IUD is of great importance and is often the determining factor in deciding whether or not a field trial should, in fact, take place.
372
Robert Snowden
Dalkon Shield: copper versus non-copper This small-scale study (FPRU, 1974e) undertaken at four centres revealed that the inclusion of copper dust and copper sulphate in the composition of the Dalkon Shield had little or no effect on the event rate associated with pregnancy, expulsion of the device from the uterus or removal of the device following a complaint of bleeding and/or pain (Table 3). The addition of copper to the polyethylene 'mix' of the Dalkon Shield occurred at the time when the effect of copper in the uterus was being demonstrated in certain Chilean studies. It is of interest that it was copper that was added for the declared purpose of providing radio-opacity to this device. Table 3. Selected net cumulative event rates at 12 ordinal months of use per 100 users of the Dalkon Shield containing, or without, copper
Dalkon Shield With copper Without copper
Pregnancy
Expulsion
Bleeding/pain removal
No. of fittings
1-2(0-9) 0-7(0-7)
2-5(1-3) 2-5(1-3)
3-5(1-5) 6-6(2-1)
178 177
Source: FPRU (1974e) Tables II and HI, pp. 8 and 9. SE in parentheses.
Dalkon Shield and the unsuccessful use of other IUDs This single centre study was aimed at studying the retention capabilities of the Dalkon Shield among women who had experience of unsuccessful use of other IUDs (FPRU, 1974e). The results suggest that there is some justification for the claim that this device has a low expulsion rate (Table 4). Table 4. Previous unsuccessful use of an IUD; selected net cumulative event rates at 12 ordinal months of use per 100 users
Dalkon Shield (normal population) Dalkon Shield (previous unsuccessful IUD use)
Pregnancy
Expulsion
Bleeding/pain removal
No. of fittings
2-8 (0-3)
2-3 (0-3)
8-1 (0-5)
4191
4-3 (2-1)
3-3 (1-8)
5-4 (2-3)
98
Source: FPRU (1974e) Table 4, p. 18. SE in parentheses.
Recent studies in IUDs
373
Comparison of winged and F Antigon devices This double blind comparative trial at ten centres produced some interesting results (Table 5) but difficulty was encountered in the fitting of the device (both models) in a large number of cases. By including a flexible membrane in the centre of the device the F model provides a greater area of contact with the endometrium without increasing the overall size of the device. The future of this device is still not clear but those who look first to the pregnancy rate can find some encouragement here. Table 5. Comparison of two models of the Antigon device; selected net cumulative event rates at 12 months of use per 100 users Antigen device Winged model F model
Pregnancy
Expulsion
1-1 (0-8) 0-5 (0-5)
6-5 (1-8) 5-2(1-6)
Bleeding/pain removal
No. of fittings
8-5 (2-1) 10-4 (2-3)
201 209
Source: Data held at the FPRU; report in press. SE in parentheses. New devices with little or no UK evidence from independent trials
The FPRU has been asked to look at a number of devices, some of which have been assessed by referee teams in various parts of the UK. (1) The Latex Leaf device (Text-fig. 2) has been assessed and rejected in its present form; the thread tended to tear through the device on removal and fears were expressed concerning the use of latex rubber in the uterus. Further laboratory evidence has been requested (FPRU, 1973). (2) The LEM device (Text-fig. 3) has been assessed and rejected (FPRU, 1974c). (3) The Copper Omega (Text-fig. 4) has been assessed and encouragement for further clinical trials has been offered to the inventor (FPRU, 1974d). Other devices have been produced but independent assessment in the UK has yet to be undertaken on any scale. There are also other devices used in other parts of the world, such as the Weiss device, the Techna Fluid Filled IUD, the Pleated Membrane, the Alza T, and Provera 7; the list could be extensive. By providing a backward look to the early 1960s when it was claimed by some that the IUD would solve the world population crisis (Guttmacher, 1965; Lloyd, 1965) some lessons can be learned. Perhaps the most important one is that new technology may not be the hoped for answer in the search for an IUD with a zero pregnancy rate. A careful examination of what is already known might be more useful.
374
Robert Snowden
Text-fig. 2. The Latex Leaf intrauterine device.
Copper wire 2001 mm2
Device in fundus of uterus
Head of device
Nylon threads
Text-fig. 3. The LEM intrauterine device. Text-fig. 4. The Copper Omega intrauterine device.
Recent studies in IUDs
375
References M.E., SILBERMAN, E. & STONE, M. (1969) The M, a new intrauterine contraceptive device. Am. J. Obstet. Gynec. 105, 279. CULLITON, B. & KNOPMAN, D. (1974) Dalkon Shield affair: a bad lesson in science and decisionmaking. Science, N. Y. 185,839. FPRU (1972) Description of Unit and National IUD Network. Report No. 1, Family Planning Research Unit, University of Exeter. FPRU (1973) Preliminary Assessment of the Latex Leaf. Report No. 5, Family Planning Research Unit, University of Exeter. FPRU (1974a) United Kingdom Field Trial of the Dalkon Shield. Report No. 7, Family Planning Research Unit, University of Exeter. FPRU (1974b) United Kingdom Field Trial of the Gravigard Device. Report No. 8, Family Planning Research Unit, University of Exeter. FPRU (1974c) Preliminary Assessment of the LEM Intrauterine Device. Report No. 9, Family Planning Research Unit, University of Exeter. FPRU (1974d) Preliminary Assessment of the Copper Omega Intrauterine Device. Report No. 10, Family Planning Research Unit, University of Exeter. FPRU (1974e) Two Dalkon Shield Studies. Report No. 12, Family Planning Research Unit, University of Exeter. FPRU (1974f) Progress Report April \912~June 1974. Report No. 14, Family Planning Research Unit, University of Exeter. GUTTMACHER, A.F. (1965) Intra-uterine contraceptive devices. /. Reprod. Fert. 10, 115. LARDNER, T., SHACK, W., TAM, P., BELSKY, R. & SCHUBECK, F. (1970) IUD Information Handbook. The Pathfinder Fund, Boston, USA. LLOYD, R. (1965) Proposal for a World Family Plan. Int. Dev. Rev. 7, 4. SNOWDEN, R. (1971) Social Factors in the Use and Effectiveness of the Intrauterine Device. Ph.D. thesis, University of Exeter. TIETZE, C. & LEWIT, S. (1970) Evaluation of intrauterine devices: ninth progress report of the Cooperative Statistical Program. Stud. Fam. Plann. No. 55, 1. CHAFT,
