A Randomised Trial and a Comparative Study of the Copper 7 200 and the Multiload Copper 250 Intrauterine Devices

Summary: A randomized trial of the Copper 7 200 (Cu 7 200) and the Multiload Copper 250 (ML Cu 250) intrauterine devices (IUD) was carried out for 13 months. On life table analysis at 12 months, net cumulative closure rates for use-related terminations (net rates) for the Cu 7 200 were higher than for the ML Cu 250 for accidental pregnancy (NS), expulsions (P<0.02) and medical removals for pain and/or bleeding (P<0.01). The continuation rate was lower for the Cu 7 200 (P<0.001). In a larger comparative study, at 12 months there was a highly significant difference (P<0.001) in favour of the ML Cu 250 in accidental pregnancy, expulsions and removals for pain and/or bleeding and continuation of use.
Since the ultimate purpose of the use of an IUD is pregnancy protection with a minimum of side effects, the continued use of the Cu 7 200 is not recommended.     

Efficacy of the Dalkon Shield in Contraception

Summary: The Dalkon Shield was inserted in 180 multiparous women. Altogether 162 women-years were available for study. In contrast to earlier studies, it was found that the pregnancy rate of 3.7 per 100 women-years was higher than that of the Lippes Loop and the Double Coil while the expulsion and medical removal rates were similar. The Dalkon Shield did not appear to have any significant advantage over the Lippes Loop.     

Long-term use of intrauterine contraceptive devices in a private practice

Clinical experience with 1504 insertions of intrauterine contraceptive devices (Lippes Loop, Dalkon Shield, Cu-7) in a private practice is evaluated. Expulsion rates and removal rates for bleeding and/or pain and personal reasons differed for the three types of devices. Pregnancy rates associated with use of the three types of devices were similar. Pelvic inflammatory disease rates were similar for Dalkon Shield and Cu-7 users but were higher than the rate for Lippes Loop users. Use of intrauterine contraceptive devices did not appear to compromise future fertility based on the experience of women who had the devices removed. The study shows that long-term IUD use (up to 5 years) provides a safe and effective method of contraception.     

Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings.

OBJECTIVE: To compare the findings of the case-control and cohort studies used to indict the Dalkon Shield (A.H. Robins Company, Inc., Richmond, VA) with the findings of the Dalkon Shield clinical trials. DATA IDENTIFICATION: All published reports on the Dalkon Shield were identified through MEDLARS system (United States National Library of Medicine) searches and by cross checking all references in these reports. The same approach was used to identify all case-control and cohort studies of the purported relationship between intrauterine devices (IUDs) and pelvic inflammatory disease (PID). STUDY SELECTION: Only studies of interval patients that included 50 or more women and 6 or more months of follow up that computed standard IUD event rates (rates of pregnancy and expulsion and removal for pain and bleeding) were selected for this study. All case-control and cohort studies identified were included except two case-control studies that included women with sterile chronic salpingitis. RESULTS: The 16 case-control and 2 cohort studies found or suggested that the Dalkon Shield increased the risk of PID. The 71 clinical trials of the Dalkon Shield show that when this device is inserted by an experienced clinician it is a safe and effective contraceptive method, comparable with other IUDs used at the time. There was no evidence of an increased risk of PID found in these clinical trials. CONCLUSIONS: This study offers convincing evidence that the indictment of the Dalkon Shield was a mistake. Additionally, this study shows that physician skill and experience is far more important to successful IUD insertion than previously recognized, a finding with considerable implications for IUD study designs and for marketing strategies.     

Increased arterial catecholamines in pre-eclampsia

Arterial and venous plasma catecholamines were measured in 13 pre-eclamptic and 13 normotensive pregnant women. In the pre-eclamptic group, arterial concentrations were higher for adrenaline (p less than 0,001), noradrenaline (p less than 0.05) and dopamine (p less than 0.01) than in the normotensive group, whereas in venous plasma only adrenaline (p less than 0.01) and dopamine levels were higher (p less than 0.05). Arterial adrenaline concentrations in the pre-eclamptic group were, on average, three times as high as normotensive arterial adrenaline. The arterial-venous (a-v) differences were higher for adrenaline (p less than 0.001) and dopamine (p less than 0.05) in the pre-eclamptic than in the normotensive group. In the pre-eclamptic group, arterial adrenaline was correlated with mean arterial blood pressure (r = 0.89, p less than 0.001) and with increased heart rate (r = 0.78, p less than 0.01). According to these results, both sympathetic nervous and sympathetic adrenal activities are increased in patients with pre-eclampsia.     

Thelarche: psychosocial aspects for gynaecology. Psychometric investigation in 533 women (author's transl)

The psychosomatic and psychosocial importance of the thelarche for gynaecology was the subject of an investigation in 533 women. Psychometrically personality traits (FPI) and intelligence level (MWT) were examined. Thelarche started the earlier the younger the women examined (p less than 0.001). Women with higher school leaving age and above-average intelligence went through thelarche earlier than those with lower school leaving age (p less than 0.01) and below-average intelligence (p less than 0.01). Breast development in the phase of puberty was observed with greater attention by younger women with higher level of education than by older women with lower level of education (roughly estimated by school leaving age and intelligence level). Thelarche was observed with greater attention by sociable, vivacious, extrovert women than by unsociable, introvert women (p less than 0.001). Women who consciously observed their breast development reported very regular cycles more often than expected (p less than 0.05) and mostly were of ideal weight (p less than 0.001). The practical importance of the thelarche experience for gynaecology manifests itself above all in the breast prophylaxis behaviour. The more attentively the women observed their breast development the more importance they attached to prophylactic medical breast examinations (p less than 0.01) and the more frequently they examined themselves (p less than 0.01) which worried them more rarely (p less than 0.05). The effect of the thelarche experience on future breast prophylaxis behaviour underlines the importance of early health education for preventive gynaecology.     

An association between the Dalkon Shield and complicated pregnancies among women hospitalized for intrauterine contraceptive device--related disorders.

A nationwide mail survey of virtually all physicians likely to be involved with intrauterine contraception resulted in 3,502 unduplicated reports of intrauterine contraceptive device (IUD)--related hospitalizations during the first six months of 1973. Dalkon Shield use was significantly more frequent among women hospitalized for a complicated pregnancy than those hospitalized for a non-pregnancy-related disorder. Although the observed association was not substantially altered by stratifications of the mail survey reports by the patient's age, race, or geographical region, the association did not apply to those women whose IUD's were explicitly reported to be of the nulliparous size. Interviews conducted with a probability sample of physicians who had not responded to the survey confirmed that the association between the Dalkon Shield and complicated pregnancy also existed in their experience. An association between the standard Dalkon Shield and complicated pregnancies might reflect an increased rate of pregnancy with this device, an increased rate of complications occurring after zygotic implantation, or perhaps both. Whatever the explanation, the observed association is sufficiently widespread to require further investigations.     

Early postpartum insertion of an intrauterine device

Over a 2-year period in London, Dalkon Shield IUDs were inserted in 162 patients during the postpartum period, usually on the 5th day. To insert the IUD, a sterile bivalve speculum was inserted in the vagina and the cervix swabbed with .5% aqueous chlorhexidine. The anterior lip of the cervix was grasped with a sponge holding forceps and the depth of the uterine cavity was assessed with uterine sound. A Dalkon Shield was inserted at the fundus of the uterine cavity using a standard type carrier. The device was correctly placed in 86.4% of the 162 patients at the 6-week postnatal examination. 22 patients expelled the device completely or partially, 3 patients were diagnosed as being pregnant with the device in situ, and 1 patient was pregnant due to expulsion. At the first menstrual period, 32 women noted heavier bleeding and 2 patients complained of increased discomfort; however, there was no undue discomfort at subsequent menses. This pilot study assessed the practicability of establishing an IUD during a woman's stay on the postnatal ward. however, the rate with Lippes Loop and Saf-T-Coil was unacceptably high. The Dalkon Shield is no longer in use, but this type of IUD with its low expulsion characteristics may successfully be applied to early puerperium. A clinical trial of the Multi-load 250, similar to the Dalkon Shield, is commencing in the near future.     

Intrauterine contraception in nulliparas with the Dalkon shield

The small Dalkon Shield was used for intrauterine contraception in a series of 1,697 nulliparous women over a 2 year study period. Of these women 80 per cent were nulligravid. The device is well tolerated and has low expulsion and medical removal rates. The pregnancy rate of 1.2 per cent remained constant after 12 months of use. The nulliparous model Dalkon Shield is an effective and extremely acceptable means of intrauterine contraception in the nulliparous female.     

Cervical Chlamydia trachomatis infection in university women: relationship to history, contraception, ectopy, and cervicitis

Endocervical Chlamydia trachomatis infection was found in 13 of 162 volunteer female university students (8%). Infection was correlated with younger age (p less than 0.05), less than or equal to 4 years of intercourse (p less than 0.05), a history of gonorrhea (p less than 0.01), and exposure to a partner with urethritis (p less than 0.01). Women who used intrauterine or barrier contraception had less infection (2%) than did women who used oral contraception (14.3%, p less than 0.05) or none at all (10.7%, p less than 0.05). Infection was strongly associated with a cervicitis score calculated from erythema, ectopy, discharge, and secretions that contained white blood cells (p less than 0.0001). By multivariate analysis, a proposed clinical approach was arrived at for testing for chlamydial organisms all women with cervicitis who were not using barrier contraception. The positive predictive value of this approach for chlamydial infection was 28%, and the negative predictive value 98.4%. Cervical ectopy was increased in women who used oral contraception (p less than 0.01), and infection was increased in women with ectopy, regardless of their contraceptive method (p less than 0.001). These results will aid in more rapid diagnosis of endocervical chlamydial infection and in the choice of contraception in young women and high-prevalence groups.     

Intrauterine contraception in multiparas with the Dalkon Shield

The large Dalkon Shield was used for intrauterine contraception in a series of 2,370 multiparous women over a 24 month study period. The device is well tolerated and has low expulsion and medical removal rates. The pregnancy rate was 1.3 per cent at 12 months and increased to 1.5 per cent at 18 months; it remained constant thereafter. The multiparous model of the Dalkon Shield is an effective and extremely acceptable means of intrauterine contraception.     

Analysis of minor complications in copper IUD wearers

Minor complications occuring after insertion of 3216 copper IUDs between October 1976 and December 1980 were studied. 1813 of the device were Cu 7 200s, 176 were Cu T 200s, 237 were ML Cu 250s, and 990 were Nova Ts. 133 partial and 71 total expulsions, 21 removals for bleeding, 24 for pain, 10 for bleeding and pain, and 115 for other causes were studied. 5.23% of Cu 7 200, 4.54% of Cu T 200, 2.53% of ML Cu 250, and 2.42% of Nova T devices were partially expelled, while 3.23% of Nova T, 1.87% of Cu T 200, 1.68% of ML Cu 250, and .56% of Cu T 200 devices were totally expelled. Considering all types of IUD, the frequency of expulsions declined with age, but great differences were not observed in relation to parity. 67.6% of total and 48.9% of partial expulsions occurred in the 1st 6 months of use. All total expulsions in the ML Cu 250 and the Cu T 200 occurred in the 1st 3 months. 58.14% of partially expelled IUDs which were reinserted presented no further problems. 16 of 21 IUDs removed for bleeding were Cu 7 200s, 2 each were ML Cu 250s and Nova Ts, and 1 was a Cu T 200. Slightly over 1/2 were removed in the 1st year of use. 20 fo the 24 IUDs removed for pain were Cu 7 200s, and 37.5% of them were used by nilliparas. 9 of the 10 removed for pain and bleeding wer Cu 7 200s, 40% of them in nulliparas. Psychological intolerance of the method (63.35%) and removal by other doctors (18.26%) were the other causes of removal. For the Cu 7 200, Cu T 200, ML Cu 250 and Nova T respectively, the Pearl indices of expulsion were 1.97, 2.22, 2.76, and 4.89, while for pain and/or bleeding they were 1.39, 1.33, 1.18, and .29.     

Plasma levels of gastrin, somatostatin, VIP, insulin and oxytocin during the menstrual cycle in women (with and without oral contraceptives)

The aim of the present study was to investigate whether plasma levels of gastrin, somatostatin, insulin, oxytocin, VIP and blood glucose levels vary during the menstrual cycle. Therefore, 19 healthy menstruating women (5 of whom were on low-dose oral contraceptives, o.c.) were blood sampled every second to third day during the menstrual cycle. Hormone levels were measured with radio-immunoassay. Gastrin, insulin, VIP and blood sugar levels remained unchanged during the menstrual cycle. Mean somatostatin levels were significantly lower in women receiving o.c. than in women without such medication (p less than 0.05). In women on o.c., somatostatin concentrations were also significantly lower during the menstrual week, than during the rest of the period (p less than 0.01), but in women without o.c., no such change occurred. Mean oxytocin levels were significantly higher in women on o.c. (p less than 0.001) and in these women, oxytocin levels recorded during the menstrual week were significantly lower than during the rest of the period (p less than 0.02). Systolic and diastolic blood pressure values were also significantly higher in women on o.c. (p less than 0.05 and p less than 0.01). In conclusion, these data show that basal plasma concentrations of gastrin, somatostatin, VIP, insulin and glucagon do not vary during the menstrual cycle. However, ingestion of low-dose oral contraceptives causes a significant decrease of somatostatin concentrations and a significant increase in oxytocin levels, suggesting that low doses of estrogens and/or gestagens may influence digestive and metabolic processes.     

Serum gonadotrophins, prolactin and ovarian steroids in primary dysmenorrhoea.

Serum samples were collected from 27 women with incapacitating primary dysmenorrhoea and from 16 normal women in the early part of the cycle (between day 3 to 6), at midcycle (between days 13 to 16) and in the late part of the cycle (between days 23 to 26) for determination of FSH, LH, prolactin (PRL), 17 beta-oestradiol (E2) and progesterone (P). The gonadotrophin and P levels showed normal and similar ovulatory patterns in both groups. The PRL concentrations (mean +/- SD) in dysmenorrhoeic women were lower than normal in the early part (9.2 +/- 4.0 ng/ml vs 14.5 +/- 7.3 ng/ml, p less than 0.01) and in the late part of the cycle (11.7 +/- 5.2 ng/ml vs 16.5 +/- 10.2 ng/ml, p less than 0.05), but not so at midcycle (9.1 +/- 2.8 ng/ml vs 10.4 +/- 4.4 ng/ml, p greater than 0.05). The E2 level was higher than normal in dysmenorrhoeic women in the late cycle (163.0 +/- 76.7 pg/ml vs 93.3 +/- 64.3 PG/ML, p less than 0.01), but apart from this the ratio of E2/P did not differ between the groups. These hormonal changes may be related to an excessive production of endometrial prostaglandins in primary dysmenorrhoea.     

Effects of intravenous terbutaline on maternal circulation and fetal heart activity

The effects of terbutaline on maternal circulation and fetal heart activity were studied in 15 healthy pregnant women admitted for external cephalic version. The two-step infusion of terbutaline (5-10 micrograms/min) resulted in increases in maternal heart rate (p less than 0.001), cardiac output (p less than 0.001), systolic arterial pressure (p less than 0.001) and pulse pressure (p less than 0.001), while diastolic arterial pressure (p less than 0.001) and total peripheral vascular resistance (p less than 0.001) were reduced. Mean arterial pressure was unchanged after the infusion. Fetal heart activity assessed by cardiotocography showed a gradual increase in baseline fetal heart rate (p less than 0.01) and an increased percentage acceleration time (p less than 0.05). Fetal movements also increased during the infusion (p less than 0.05). The terbutaline infusion had a positive inotropic effect and produced decreased systemic vascular resistance in the pregnant woman, and placental transfer of the drug resulted in increased fetal heart activity. The potential influence of the drug-induced changes in maternal hemodynamics on utero-placental perfusion require further investigation.     

Effects of danazol on serum lipid and lipoprotein levels in patients with endometriosis

Danazol was given to 16 patients with endometriosis in daily doses of 200 to 400mg for 4 to 6 months, and the change in serum lipids and lipoproteins was analysed. Danazol decreased total cholesterol by an average of 22%, triglycerides by 56%, phospholipids by 29%, free fatty acids by 17% and lipid peroxides by 42%, among which reductions in total cholesterol (p less than 0.05) and lipid peroxides (p less than 0.01) were statistically significant when compared with the pretreatment levels. Levels of lipids in HDL and VLDL also fell: HDL-cholesterol by 43%, HDL-triglycerides by 68%, HDL-phospholipids by 40%, VLDL-cholesterol by 73%, VLDL-triglycerides by 71% and VLDL-phospholipids by 48%. The decrease in HDL-cholesterol (p less than 0.05), HDL-triglycerides (p less than 0.05) and HDL-phospholipids (p less than 0.001) was significant. Concurrently apolipoproteins and LCAT activity decreased: A-I by 28% (p less than 0.001), A-II by 7% (p less than 0.05) and LCAT by 35%. In contrast, LDL-cholesterol increased, though slightly. Therefore, the atherogenic index defined as the ratio of LDL-c/HDL-c rose as much as 98% of the initial value. These changes seem to have arisen from impairment in the VLDL-HDL cycle. The decrease in VLDL and increase in LDL indicated that VLDL was catabolised and converted to LDL at a normal rate while the formation of HDL was impaired probably due to the low activity of LCAT and low level of apo A-I and A-II.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind study comparing ritodrine and terbutaline in the treatment of preterm labor

One hundred women in preterm labor were randomly treated with ritodrine or terbutaline in a double-blind fashion. The drugs were comparably effective during intravenous therapy but, in women with intact membranes, an oral dose of terbutaline, 30 mg daily, was significantly more effective than ritodrine, 120 mg daily, in preventing recurrent labor during a 5-day course of oral therapy (one of 19 versus 12 of 23, p less than 0.001). In women with intact membranes, pregnancy was prolonged 40 +/- 25 days (mean +/- SD) in women receiving terbutaline orally and only 22 +/- 24 days in women receiving ritodrine orally (p less than 0.01). In women with intact membranes, a heart rate greater than or equal to 130 bpm occurred in in a higher proportion of women receiving intravenous treatment with ritodrine than among those receiving terbutaline (20 of 31 versus 8 of 27, p less than 0.05). Terbutaline-treated women, however, were significantly more likely to have a serum glucose level in excess of 140 mg/dl than were women treated with ritodrine (13 of 26 versus 6 of 29, p less than 0.05). Side effects commonly observed during intravenous therapy included nausea (22%), chest pain (15%), and shortness of breath (15%). Side effects were significantly (p less than 0.025) more likely to occur during periods when the infusion rate was being increased rather than during periods when the infusion rate was constant.     

Prostaglandins in peritoneal fluid of women with minimal and mild endometriosis]

Peritoneal fluid from 52 women with minimal and mild endometriosis was aspirated at laparoscopy and PGs were analyzed. Peritoneal lesions were classified into black, red and white lesions and peritoneal pockets, and were excised and pathological examination performed. Patients were classified into the black lesion group (n = 17) and the red lesion group (n = 35) according to the main colour of the lesions. 1. Endometrial gland and stroma were found in 78% of black lesions, 53% of red lesions, 60% of white lesions and 62% of peritoneal pockets. Infiltration of lymphocytes was found in 74% of black lesions, 83% of red lesions, 80% of white lesions and 77% of peritoneal pockets. 2. The fluid volume of the red lesions group was significantly higher than that of the control group (p less than 0.01). But the fluid volume of the black lesions group was insignificant as compared with that of the control group. 3. The PGE2 and PGF2 alpha concentrations in fluid from the red lesion group were significantly higher than not only the control group (p less than 0.001, p less than 0.05) but also the black lesion group (p less than 0.01, p less than 0.05). Only the PGE2 concentration in fluid from the black lesion group was significantly higher than that of the control group (p less than 0.001). 4. In the red lesion group which had no infertility factors without endometriosis, 20 of 25 patients achieved pregnancy (80%) in a one-year follow up. This was significantly higher than in the black lesions group (44%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Earth, motherhood, and the intrauterine device.

Commentary is provided on the relationship between the use of the IUD and infertility from the development of pelvic inflammatory disease (PID), preventive behavior for those using an IUD, and recent reviews of the Dalkon Shield. Among IUD users who have never been pregnant, tubal infertility is increased 2-6 fold (200-600%), and most with tubal infertility will never bear a child. Tubal infertility develops in 11% of patients with PID, but most IUD users do not develop PID. The physicians responsibility is 1) to give formal and extensive recognition to the connection that IUD uses causes PID; 2) to inform patients of the potential risk of PID and sterility; 3) to develop proper patient selection for an IUD; 4) to identify and treat PID, which may appear initially as abnormal uterine bleeding and mild pain; 5) to recognize that the IUD facilitates the development of PID in patients with Neisseria gonorrhoea and Chlamydia trachomatis even though 25-50% of IUD patients have neither infection; 6) to recognize that the risk of PID is increased in the first 4-6 months of insertion and to research alternatives, e.g. the use of available antibiotics to treat selected patients to reduce infections, and 7) to realize that most PID occurs 6 months after insertion and indolent abscess formation is expected to increase among longterm copper IUD users. The reviews referred to in this article are ones claiming unfair removal of the Dalkon Shield in 1974 based on flawed study design and analysis of case control and the understanding that the Dalkon Shield is no worse than other IUDs and not related to PID. The author points out that neither review mentions that primary tubal infertility increased 6-fold among Dalkon Shield users who had used only 1 IUD in their life, and that infertility increased 3-fold among IUD users compared with the non-IUD using population. The case control studies provide enough evidence for the cause and effect relationship. The Kronmal et al. article did not present convincing new evidence even with reanalysis of the original Lee et al. data. In the Memford and Kessel review case controlled studies are excluded from consideration. Most PID goes unrecognized. The rate of PID cannot be determined. The goal is to protect patients and reduce population. The enemy is not physicians with opposing positions on this issue.     

Evaluation of fetal and neonatal mortality at the University Hospital of Troms?, Norway, from 1976 to 1989.

To investigate developments in perinatal care, all fetal and neonatal deaths among those born after at least 24 weeks of gestation at the University Hospital of Troms?, Norway from 1976 to 1989, were subjected to medical audit. A decrease in total mortality rate was found when based on maturity (greater than or equal to 24 weeks; 19.9-13.4%; p less than 0.01), and/or birth weight (greater than or equal to 500 g; 19.2-13.4%; p less than 0.05). This was mainly due to a decrease in fetal deaths (14.8-6.6%; p less than 0.0001). Deaths during labor (5.4-1.1%; p less than 0.001), and deaths before the onset of labour (9.4-5.5%; p less than 0.05) declined. The neonatal death rate remained virtually constant (5.2-6.8%). The incidence of conditions affecting the placenta and the umbilical cord, causing asphyxia and intra-uterine growth retardation, declined, from 9.2 to 5.0% (p less than 0.01), as did that caused by immaturity (2.8-1.3%; p less than 0.05). The rates of death caused by cerebral hemorrhage, respiratory distress syndrome, infections, and malformations did not change. There was no significant proportional change in the causes of death from the first to the last period. The rate of fetal death following suboptimal care declined (2.4-0.4%; p less than 0.01), while the corresponding neonatal death rate remained unchanged (0.9-1.1%). The proportions of both fetal and neonatal deaths occurring after suboptimal care were low (fetal: 16.2, 8.8, and 5.6%; neonatal: 17.1, 23.5, and 16.2%). These differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)