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Of Conception in Women Becoming Pregnant with a Copper-Bearing IUD in Situ Christine Gosden, A

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Of Conception in Women Becoming Pregnant with a Copper-Bearing IUD in Situ Christine Gosden, A The state of the device and copper levels in the products of conception in women becoming pregnant with a copper-bearing IUD in situ Christine Gosden, A. Ross, A. McGovern and W. Reid MRC Clinical and Population Cytogenetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU; *MRC Brain Metabolism Unit, 1 George Square, Edinburgh; and ^Department of Obstetrics and Gynaecology, Eastern General Hospital, Seafield Road, Edinburgh, UK. Summary. Of the 8 pregnancies studied, 2 were of small gestational sacs with blighted ova and were associated with devices in which the copper wire had very high detectable X-ray emissions for copper (>90%). In 2 other pregnancies intrauterine deaths had occurred by the time of termination at 13 and 17 weeks and copper levels in the products of conception were variable. There was no abnormality of the fetus in the term pregnancy but it seems possible that copper can affect the early growth and development of the embryo. On only 1 of the 8 devices was any great amount of calcium deposited and it is therefore considered unlikely that calcium deposition increases the risk of pregnancy by preventing the release of copper. Introduction When copper wire is wound round an inert plastic intrauterine device, the copper seems to increase the contraceptive efficiency of the device. The way in which the copper is thought to exert this effect is not known, but it is believed to involve some toxic effect upon spermatozoa, ovum, blastocyst, embryo, uterine milieu or enzyme systems. The role of copper on mammalian reproduction has been comprehensively reviewed by Oster & Salgo (1977). Our recent findings (Ross, Gosden, Loudon & Foxwell, 1978) that the copper wire of a copper-bearing intrauterine device becomes coated with a layer of calcium in some women, but not in others, shows that there are different uterine responses to the device. As the deposition of calcium appears to inhibit the erosion of copper, the question arises whether the risk of pregnancy is greater in women in which the IUD becomes calcified. This paper reports our findings of copper-bearing intrauterine devices removed from women who became pregnant with the device in situ. We also examined the products of conception and measured their copper levels for correlation with the state of the device. Case histories Patient 1 This woman began vaginal bleeding at 9 weeks gestation and at 10 weeks a gestational sac was spontaneously aborted. This intact blood-filled sac contained a small embryo of 2 mm crown-rump length. The sac was consistent in size with a gestation of 10 weeks. A dilatation and curettage evacuation of the uterus was performed and the intrauterine device was removed. Downloaded from Bioscientifica.com at 10/07/2021 09:25:11AM via free access Patient 2 Vaginal bleeding began at 9% weeks gestation and the IUD was removed and sent to the laboratory for analysis. After 3 days of heavy blood loss per vaginam a dilatation and curettage were carried out. The gestation was estimated at 10 weeks from measurements of the fetal limb and 10 weeks by dates. Patient 3 This patient requested termination of pregnancy at an estimated gestation of 10 weeks by dates. This was carried out by suction evacuation, and the IUD was removed at the same time. There was no evidence of a fetus and only portions of sac estimated at about 8 weeks in size which may have contained a blighted ovum or very small embryo. Patient 4 This patient requested termination of pregnancy. The device was removed immediately before termination was induced with prostaglandin E-2 administered extra-amniotically. The patient's gestation was 16 weeks by dates but the macerated male fetus which was delivered had a crown-rump length of 8 cm and a heel-toe length of 1-2 cm, giving an estimated gestation based on size of only 13-14 weeks. The fetus had no major external abnormalities and no major organ system abnormalities were detected. Patient 5 The device was removed at 5^ weeks gestation and sent to the laboratory for SEM and X-ray microprobe analysis. The patient then requested termination of the pregnancy which was carried out at 8 weeks. The products of conception were not available for study. Patient 6 The tail of the IUD was seen at the first examination after the positive pregnancy test, but the device was not removed. Labour was induced at 41 weeks gestation. The IUD was removed immediately before artificial rupture of the membranes. There was a forceps delivery of a live male child who cried immediately and had Apgar scores of 9 at 1 min and 10 at 5 min. The child had no external abnormalities. Patient 7 When the pregnancy test was positive at 5 weeks gestation, the device was removed and sent to the laboratory to be processed for SEM and X-ray microprobe analysis. The patient requested early termination of pregnancy. The products of conception were not available for study. Patient 8 The pregnancy test was positive at 5 weeks. At 20 weeks gestation no fetal heart could be detected. Since the fetus had died in utero, abortion was induced with prostaglandin E-2 administered extra-amniotically after removal of the IUD. After 18 h a macerated female fetus was delivered. The fetus had a crown-rump length of 12-5 cm indicating a gestation of 17 weeks by size. There were no major external or internal abnormalities. The IUD was not available for study. Downloaded from Bioscientifica.com at 10/07/2021 09:25:11AM via free access Patient 9 This fetus was used as a control when the pregnancy of a 22-year-old healthy woman who was using no contraception was terminated for social indications. Complete abortion occurred 16 h after prostaglandin E-2 was administered extra-amniotically. The fetus appeared fresh, was not macerated, and careful examination revealed no major external or internal abnormalities of the fetus. Materials and Methods When removed from the patient the copper IUDs (Gravigard devices, Searle) were placed into dry sterile containers and immediately transported to the laboratory. The device was cut into small portions and each was mounted onto an aluminium stub, dried in a dessicator and finally coated with a layer of carbon. One portion of the dried IUD was embedded in Araldite (CIBA) and cut to give cross-sections of the device which were then mounted and coated with carbon. All available products of conception, including material from dilatation and curettage in theatre, were collected into dry sterile containers and transported to the laboratory. All specimens were examined, photographed, weighed and measured. Samples were removed for estimation of copper levels and for study of embryonic development, histology, tissue culture and cytogenetic studies (Gosden, Wright, Paterson & Grant, 1976). Small specimens and incomplete portions of tissue were examined under a dissecting microscope before further study. The remainder of the products was preserved in buffered formalin. Electron microscopy and X-ray analysis All specimens of the IUDs were examined and photographed with a scanning electron microscope (Stereoscan S180, Cambridge Instruments Ltd) fitted with an X-ray microprobe analyser (Link Systems Ltd). The accelerating voltage used was 30 KeV as described previously (Gosden, Ross & Loudon, 1977). Atomic absorption spectrophotometry to estimate copper Aliquots of tissue were weighed into small plastic tubes (Eppendorf) and digested in 1-5 m- nitric acid at 80°C for 6 h and then at 105°C to dryness. The residues were then re-dissolved in 500 ul distilled water. Flameless atomic absorption analysis was carried out with an atomic absorption spectrophotometer (Model 360: Perkin-Elmer), fitted with a heated graphite atomizer (Regan & Warren 1976). Copper was estimated at a wavelength of 324-7 nm. Aqueous solutions of cupric nitrate (B.D.H. Poole, Dorset) containing 0-1, 0-2 or 0-4 pg copper/ml were prepared as standards. All solutions were made up in de-ionized distilled water. Each sample (50 ul) was injected into the graphite furnace and after the initial pre-drying period to reduce spraying, the material was dried, thermally destroyed and atomized. Argon was the inert gas used (flow rate 300 ml/min), the gas stop mode being selected during atomization. Specimens with a concentration above the standards were further diluted (Sperling, 1976). Results The results are summarized in Table 1. As shown in Figs 1(b)—7(b), the surfaces of the copper wire from the 7 devices available for study by scanning electron microscopy were very different from the smooth surface of an unused device. Figures l(c)-7(c) illustrate the cross-sections of the wire and Figs l(a)-7(a) represent the X-ray emissions from the surface of the wire. 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