A prospective randomized study to compare the use of repeated doses of vaginal with sublingual misoprostol in the management of first trimester silent miscarriages

BACKGROUND: A randomized controlled trial comparing sublingual with vaginal administration of misoprostol for medical management of silent miscarriages. METHODS: Eighty women who had silent miscarriages (<13 weeks) were randomized to receive 600 micro g of misoprostol every 3 h for a maximum of three doses either sublingually or vaginally. RESULTS: The success rates of medical management were the same in both groups (87.5%; 95% CI: 74-95%). There were no serious complications. The incidence of diarrhoea was higher in the sublingual (70%) than the vaginal route (27.5%) (P < 0.005). Other side effects were similar in each group, although fatigue was experienced by more women in the sublingual group than in the vaginal group (65 versus 40%: P = 0.043). The overall acceptability of medical management was good. Most women would choose the medical method if they were allowed to choose again and would recommend the method to others. CONCLUSION: The current regimen of misoprostol is useful for the management of silent miscarriage in terms of complete miscarriage rate and patient acceptability. Sublingual misoprostol may offer an alternative for women who do not like repeated vaginal administration of the drug.     

A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage

BACKGROUND: This randomized controlled trial compared the use of sublingual misoprostol with or without an additional 1 week course of sublingual misoprostol for the medical management of silent miscarriage. METHODS: A total of 180 women who had silent miscarriage (<13 weeks) was given 600 microg of misoprostol every 3 h for a maximum of three doses. These women were randomized into two groups: (i) no extended course of misoprostol or (ii) an extended course of sublingual misoprostol 400 microg daily for 1 week. The primary outcome measure was complete miscarriage rate. RESULTS: The success rates for complete miscarriage were similar in both groups (group 1: 92.2%; 95% CI: 86.1-97.5% and group 2: 93.2%; 95% CI: 84.6-96.8%). There were no serious complications. The incidence of diarrhoea was higher (P < 0.01) in the group with an extended course of sublingual misoprostol. Other side-effects were similar. CONCLUSION: Sublingual misoprostol is useful for the management of silent miscarriage. An additional 1 week course of sublingual misoprostol did not improve the success rate or shorten the duration of vaginal bleeding. Instead, it increased the incidence of diarrhoea.     

A prospective randomized comparison of sublingual and oral misoprostol when combined with mifepristone for medical abortion at 12-20 weeks gestation

BACKGROUND: Sublingual misoprostol has been shown to be effective in medical abortion. A prospective double-blinded placebo-controlled trial was done to compare the efficacy and side-effects of sublingual to oral misoprostol when used with mifepristone for medical abortion from 12 to 20 weeks gestation. METHODS: A total of 120 women at 12-20 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either sublingual or oral misoprostol 400 mg every 3 h for a maximum of five doses 36-48 h later. The course of misoprostol was repeated if the woman did not abort within 24 h. RESULTS: There was no significant difference (P = 0.43) in the success rate at 24 h [relative risk = 1.075; 95% confidence interval (CI): 0.94-1.19]. Abortion occurred in 91.4% in the sublingual group (95% CI: 81.0-96.7%) as compared to 85.0% (95% CI: 73.7-92.1%) in the oral group. The median induction-to-abortion interval was significantly shorter (P = 0.009) in the sublingual group (5.5 h) as compared to the oral group (7.5 h). The incidence of fever was higher in the sublingual group (P < 0.0001). The incidences of other side-effects were similar. CONCLUSION: Sublingual misoprostol, when combined with mifepristone, is effective for medical abortion in the second trimester. The induction-to-abortion interval is shorter when sublingual misoprostol is used when compared to oral misoprostol.     

A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation

BACKGROUND: A combination of mifepristone and misoprostol provides an effective method of medical abortion for early pregnancy. This is the first randomized trial comparing the use of sublingual misoprostol with vaginal misoprostol in combination with mifepristone for termination of early pregnancies up to 63 days. METHODS: A total of 224 women who requested legal termination of pregnancy up to 63 days were randomized by computer- generated list into two groups and given 200 mg of oral mifepristone followed 48 h later by either 800 micro g of sublingual (n = 112) or vaginal (n = 112) misoprostol. RESULTS: Complete abortion occurred in 98.2% (95% CI: 93-99) of women in the sublingual group and 93.8% (95% CI: 88-97) in the vaginal group. There were three ongoing pregnancies in the vaginal group but none in the sublingual group. The median duration of vaginal bleeding was 17 days. There was no serious complication. Fever, chills and gastrointestinal side-effects (nausea, vomiting and diarrhoea) were significantly more common in the sublingual group. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for medical abortion up to 63 days. Both the sublingual and vaginal are effective routes of administration. Further randomized trials are required to find out the optimal dose of sublingual misoprostol that can give the highest complete abortion rate and lowest incidence of side-effects.     

Economic evaluation of misoprostol in the treatment of early pregnancy failure compared to curettage after an expectant management

BACKGROUND: The increased pressure on health care expenses implies that physicians should consider economic aspects as part of the clinical decision-making process. Direct and indirect costs of a strategy starting with misoprostol in treatment of early pregnancy failure as compared to curettage is therefore performed. METHODS: We performed a cost-minimization analysis alongside a multicentre randomized trial. Clinical data and data on the use of medical resources were obtained from a randomized trial comparing misoprostol and curettage, which had shown that misoprostol reduced the need for curettage in 53%. In a sensitivity analysis the percentage of women who needed curettage after misoprostol varied between 25 and 90%. RESULTS: Direct costs per case were significantly lower in the misoprostol group (mean 433) than in the curettage group (mean 683) (mean difference 250, 95% CI 184 to 316, P < 0.001). These significant differences existed under a wide range of alternative assumptions about unit costs. The differences in direct cost in favour of misoprostol were large for women who had complete evacuation after initial misoprostol treatment as compared to those who needed additional curettage after failed misoprostol. Mean indirect costs were equal for both groups (misoprostol mean 486; curettage mean 428; mean difference 60, 95% CI -61 to 179, P = 0.51). The mean total costs for a strategy starting with misoprostol was 915 versus 1107 for curettage, with a mean difference between both groups of 192 (95% CI 33 to 351, P = 0.04). An increase of the complete evacuation rates for initial misoprostol therapy to 90% in the sensitivity analysis increased the cost difference between misoprostol and curettage to 550. CONCLUSION: The use of misoprostol for early pregnancy failure after failed expectant management is less costly than curettage.     

A randomized controlled trial comparing medical and expectant management of first trimester miscarriage

BACKGROUND: We aimed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception (ERPC). METHODS: Of 131 eligible women with first trimester miscarriage, 104 agreed to randomization to either 600 microg misoprostol or placebo intravaginally. They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete. Those not successful after two doses were seen on day 7, and, if miscarriage was not complete, an ERPC was performed. RESULTS: The success rate of medical management was 88.5% (46/52) compared with 44.2% (23/52) for expectant management. There was no significant difference in success rate (100 versus 85.7%) in women treated with an incomplete miscarriage. Women with early pregnancy failure had a success rate of 87% with misoprostol compared with 29% with expectant management [odds ratio (OR) 15.96; 95% confidence interval (CI) 5.26, 48.37]. The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 (32.7 versus 5.8%) and by day 2 (73.1 versus 13.5%) of treatment. There were no differences in side-effects, bleeding duration, analgesia use, pain score and satisfaction with treatment. Women in the expectant group made more outpatient visits (5.06 versus 4.44%; OR = -0.62, 95% CI -1.04, -0.19). More women in the medical group (90.4 versus 73.1%; OR 1.26, 95% CI 1.05, 1.50) would elect the same treatment in the future. CONCLUSIONS: Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure. Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management.     

Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review

BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage and early preterm birth. It is uncertain if the outcome is improved by embryo reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER. The two groups were compared for the rates of miscarriage, defined as pregnancy loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition, systematic searches were performed to identify studies comparing outcomes in expectant management versus ER in triplet pregnancies. RESULTS: We combined data from 365 pregnancies managed in our centre with those of five previous studies. In total there were 893 pregnancies. In the ER group (n=482) compared to the expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus 4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036] and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95% CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions needed to be performed to prevent one early preterm delivery, while the number of reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS: In trichorionic triplets, ER to twins is associated with an increase in the risk of subsequent miscarriage and decrease in risk of early preterm birth.     

The questionable use of albumin for the prevention of ovarian hyperstimulation syndrome in an IVF programme: a randomized placebo-controlled trial

BACKGROUND: The role of intravenous (IV) albumin administration in the prevention of ovarian hyperstimulation syndrome (OHSS) and in the improvement of IVF conception outcomes was evaluated in a prospective, randomized, placebo-controlled double blind study. METHODS: Ninety-eight women were enrolled in the study and were consecutively assigned to either a treatment group or a control group. Eleven patients were lost to follow-up after assignment. Of the remaining 87 women, 46 received albumin on the day of oocyte retrieval, and 41 received 0.9% sodium chloride solution as a placebo control. Outcome measures included OHSS incidence rates and pregnancy rates in the two trial groups. RESULTS: Four of the 46 patients in the study group developed severe OHSS and six developed moderate OHSS. In the control group, one of the 41 developed severe OHSS and five developed moderate OHSS. The difference in OHSS incidence rates between the two groups was not statistically significant [relative risk (RR) = 1.49, 95% CI = 0.59-3.73]. Fourteen patients (30%) in the intervention group conceived, compared with 16 patients (39%) in the control group. The difference in conception rates between the two groups was not statistically significant (RR = 0.78, 95% CI = 0.44-1.39). CONCLUSIONS: Albumin appears to have no positive effect on OHSS or conception rates, while its use carries the risk of undesirable side effects, including exacerbation of ascites in OHSS, nausea, vomiting, febrile reaction, allergic reaction, anaphylactic shock and risk of virus and prion transmission. We suggest that this form of treatment should not be included in the prevention of OHSS.     

Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF.

BACKGROUND: Over the past decade attention has been increasingly focused on the long-term health effects of assisted reproductive technologies (ART), such as IVF, in both women and their offspring. To determine the risk of cancer in children conceived by IVF we used a large population-based historical cohort that was initially designed to examine the risk of gynaecological disorders in women who underwent IVF. METHODS: Children were included in the exposed group if they were conceived by IVF or other related fertility techniques (n=9484). The unexposed group consisted of 7532 children whose mothers were diagnosed with subfertility disorders but who were conceived naturally. All cohort members were asked to complete a mailed questionnaire that inquired about reproductive variables and cancer in the offspring (response rate 66.9%). RESULTS: During an average follow-up period of 6.0 years, 16 cancers were observed in the exposed and unexposed group combined, whereas 15.5 were expected [standardized incidence ratio (SIR) = 1.0; 95% confidence interval (95% CI) 0.6-1.7]. A direct comparison between children conceived after ART and naturally conceived children revealed no increased risk for childhood malignancies [risk ratio (RR) = 0.8; 95% CI 0.3-2.3]. CONCLUSIONS: Despite the small numbers of observed cancer cases, these findings demonstrate that children conceived by ART have no greatly increased risk of cancer during childhood compared with the general population and the internal reference group.     

Case management to improve major depression in primary health care: a systematic review

BACKGROUND: Deficits in the care of depression lead to poor medication adherence, which increases the risk of an unfavourable outcome for this care. This review evaluates effects on symptoms and medication adherence of case management in primary health care. METHOD: A systematic literature search was performed. The quality of the studies was rated according to the Cochrane Effective Practice and Organization of Care Group (EPOC) criteria. To conduct a subgroup analysis interventions were classified as either 'standard' or 'complex' case management. RESULTS: Thirteen studies met the inclusion criteria. In a meta-analysis we calculated a standard mean difference/effect size on symptom severity after 6-12 months of -0.40 (95% CI -0.60 to -0.20). Patients in the intervention groups were more likely to achieve remission after 6-12 months [relative risk (RR) 1.39, 95% CI 1.30-1.48]. The relative risk for clinical response was 1.82 (95% CI 1.68-2.05). Patients in intervention groups had better medication adherence than the control group (RR 1.5, 95% CI 1.28-1.86). We found heterogeneous results when assessing effects of different types of intervention. CONCLUSIONS: We conclude that case management improves management of major depression in primary health-care settings.     

Multinucleation in cleavage stage embryos

BACKGROUND: The aim was to analyse multinucleation in relation to its incidence in time and in the population, and its correlation with clinical variables, with other morphological characteristics and with the implantation rate of cleavage stage embryos. METHODS: Retrospective analysis of 10 388 cleaved embryos from 1395 consecutive IVF/ICSI cycles in 700 patients between January 1, 1999 and June 30, 2002. RESULTS: Multinucleation was observed in 3491 (33.6%) embryos in 1107 cycles (79.4%) of 609 (87%) patients, more frequently on day 2 than on day 3: 2848 (27.4%) versus 1567 (15.1%) [relative risk (RR) = 1.82; 95% confidence interval (CI) = 1.72-1.92]. Its incidence increased with fragmentation: 31.0, 34.4 and 36.5% for fragmentation 相似文献   

Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis

BACKGROUND: Laparoscopic surgery presents a large number of advantages over laparotomy. The goal of this work was to check whether these benefits outweigh any greater risk of complications. METHODS: The study design was a meta-analysis of published data from prospective randomized clinical trials (RCT). For the period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial Registers and asked the investigators for further details. Meta-analysis was carried out with the Cochrane review manager software RevMan 4.1. RESULTS: A total of 27 prospective RCT including 3611 women (1809 treated by operative laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis. The overall risk of complications was significantly lower for patients operated by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI) 0.50-0.70]. There was no statistically significant difference concerning the risk of major complications with respect to the approach used (RR 1.0; 95% CI 0.60-1.65). The risk of minor complications was significantly lower for patients operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the risks of readmission, second procedure and blood transfusion, there was no difference between the two groups. Identical results were found when we performed a sensitivity analysis including or excluding studies according to the methodological score. Subgroup analysis according to how serious the surgery was (minor, major, advanced) showed a significant increase in the risk of transfusion for advanced procedures performed by laparotomy. CONCLUSIONS: Laparoscopic surgery is not inherently dangerous for patients presenting benign gynaecological pathologies. The potential risk of complications should no longer be advanced as an argument against using laparoscopic surgery rather than laparotomy for an operation when the indication allows the choice.     

Breastfeeding history and childhood allergic status in a prospective birth cohort.

BACKGROUND: Breastfeeding provides the best possible nutrition for newborns, but its role in the development of allergies is complex. OBJECTIVE: To examine the relationship between breastfeeding and early childhood skin sensitization. METHODS: In a birth cohort of 405 children from the Childhood Allergy Study, we used maternal report to classify children's duration of breastfeeding and whether they were breastfed only, formula fed only, or both. We examined the relationships between this information and childhood allergies as determined by skin prick testing for inhalant allergens at age 6 to 7 years. RESULTS: There was no association between duration of breastfeeding and risk of allergic sensitization. Overall, children who were breastfed only were 50% more likely to have allergic sensitization than those fed formula only (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1-2.1). Although the estimates are imprecise, this RR was higher for children born to mothers reporting a history of allergy (RR, 1.8; 95% CI, 1.0-3.0) than for those born to mothers with no allergic history (RR, 1.3; 95% CI, 0.9-2.1), for children in households without (RR, 1.6; 95% CI, 1.1-2.2) vs with (RR, 1.0; 95% CI, 0.3-4.0) multiple pets, and for those with an older sibling (RR, 2.0; 95% CI, 1.2-3.3) vs firstborns (RR, 1.3; 95% CI, 0.8-2.1). CONCLUSIONS: Breastfeeding without formula supplementation may be associated with an increased risk of childhood allergies. However, this association may vary with birth order, exposure to household pets, and maternal allergic history.     

Increased longevity in older users of postmenopausal estrogen therapy: the Leisure World Cohort Study

OBJECTIVE: To examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women. DESIGN: As part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression. RESULTS: Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend <0.001). The risk was lowest among long-term (> or =15 y) users (RR = 0.83; 95% CI, 0.74-0.93 for 15-19 y and RR = 0.87; 95% CI, 0.80-0.94 for 20+ y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (< or =0.625 mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET. CONCLUSION: Long-term ET is associated with lower all-cause mortality in older women.     

Poor adherence to placebo or amiodarone therapy predicts mortality: results from the CAMIAT study. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial.

OBJECTIVE: This study examined the relationship between adherence, mortality, and psychosocial factors. METHODS: Subjects were 1141 patients participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. Poor adherence to study medication (amiodarone or placebo), measured by pill count over 2 years, was defined as the lower 20th percentile of the pill count distribution. Predictors of adherence were also studied and included demographic and cardiac variables and, in a subset of participants (N = 671), measures of depression, distress, hostility, and social support. RESULTS: In survival analysis controlling for cardiac and demographic variables, poor adherence in the placebo and amiodarone groups was associated with an increased risk of sudden cardiac death (relative risk (RR) = 2.11, 95% confidence interval (CI) = 1.03-4.56, p < .05; and RR = 3.15, 95% CI = 1.34-7.44, p < .01, respectively), total cardiac mortality (RR = 2.04, 95% CI = 1.12-3.72, p < .02; and RR = 2.49, 95% CI = 1.32-4.72, p < .01, respectively), and all-cause mortality (RR = 2.25, 95% CI = 1.27-3.97, p < .001; and RR = 2.34, 95% CI = 1.32-4.17, p < .004, respectively). Logistic regression analysis identified two predictors of poor adherence to placebo: age > 70 years (odds ratio = 2.18, 95% CI = 1.11-4.29, p < .03) and social activities in the month before the index heart attack (odds ratio = 1.02, 95% CI = 1.00-1.04, p < .05). CONCLUSIONS: Poor adherence is associated with a greater risk of mortality. The relationship between adherence and social activities suggests a higher motivation to adhere to treatment in individuals more engaged in enjoyable activities.     

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.     

Effect of body mass index on mortality of patients with lymphoma undergoing autologous hematopoietic cell transplantation.

High-dose therapy with autologous hematopoietic cell transplantation (auto-HCT) is frequently used to improve outcomes in lymphoma. However, small studies suggest a survival disadvantage among obese patients. Using a retrospective cohort analysis, we studied the outcomes of 4681 patients undergoing auto-HCT for Hodgkin or non-Hodgkin lymphoma between 1990 and 2000 according to body mass index (BMI). Four groups categorized by BMI were compared by using Cox proportional hazards regression to adjust for other prognostic factors. A total of 1909 patients were categorized as normal weight (BMI 18-25 kg/m2), 121 as underweight (BMI<18 kg/m2), 1725 as overweight (BMI>25-30 kg/m2), and 926 as obese (BMI>30 kg/m2) at the time of HCT. Outcomes evaluated included overall survival, relapse, transplantation-related mortality (TRM), and lymphoma-free survival. TRM was similar among the normal, overweight, and obese groups; the underweight group had a higher risk of TRM (relative risk [RR], 2.46; 95% confidence interval [CI], 1.59-3.82; P<0.0001) compared with the normal-BMI group. No differences in relapse were noted. Overall mortality was higher in the underweight group (RR, 1.48; 95% CI, 1.17-1.88; P=.001) and lower in the overweight (RR, 0.87; 95% CI, 0.79-0.96; P=.004) and obese (RR, 0.76; 95% CI, 0.67-0.86; P<.0001) groups compared with the normal-BMI group. In light of our inability to find differences in survival among overweight, obese, and normal-weight patients, obesity alone should not be viewed as a contraindication to proceeding with auto-HCT for lymphoma when it is otherwise indicated.     

Risk of thyroid cancer after exposure to fertility drugs: results from a large Danish cohort study

BACKGROUND: Findings from the few epidemiological studies that have investigated thyroid cancer risk after fertility drugs have been inconclusive. Using data from the largest cohort of infertile women to date, we examined the effects of fertility drugs on thyroid cancer risk. METHODS: A cohort of 54 362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of thyroid cancer associated with different fertility drugs after adjustment for age at first live birth. RESULTS: A total of 29 thyroid cancers were identified during follow-up through 2000. Use of clomiphene [RR = 2.28; 95% confidence interval (CI): 1.08-4.82] or progesterone (RR = 10.14; 95% CI: 1.93-53.33) was associated with an increased thyroid cancer risk, although the latter estimate was based on few cases. When stratifying for parity status, the risk was primarily associated with clomiphene (RR = 3.09; 95% CI: 1.21-7.88) in parous women. No significantly increased risk was found after use of gonadotrophins, hCG or GnRH. We observed no association with number of cycles of use or years since first use (latency). CONCLUSIONS: Clomiphene and possibly progesterone may increase thyroid cancer risk, particularly among parous women. Longer follow-up is needed to confirm our findings.     

The FLUSH trial--flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomized trial

BACKGROUND: To assess the effectiveness of flushing with the oil-soluble contrast medium lipiodol in women with unexplained infertility. METHODS: An open randomized controlled trial design in a single centre secondary and tertiary level infertility service setting. A total of 158 women with unexplained infertility were stratified into two populations: 96 women without confirmed endometriosis and 62 women with endometriosis who had normal Fallopian tubes and ovaries. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Lipiodol flushing was tested versus no intervention. The main outcome measures were clinical pregnancy (assessed at 6 months following randomization) and live birth. RESULTS: Lipiodol flushing resulted in a significant increase in pregnancy [48.0 versus 10.8%, relative risk (RR) 4.44, 95% confidence interval (CI) 1.61-12.21] and live birth (40.0 versus 10.8%, RR 3.70, 95% CI 1.30-10.50) rates versus no intervention for women with endometriosis, although there was no significant difference in pregnancy (33.3 versus 20.8%, RR 1.60, 95% CI 0.81-3.16) or live birth (27.1 versus 14.6%, RR 1.86, 95% CI 0.81-4.25) rates for women with unexplained infertility without confirmed endometriosis. CONCLUSIONS: Lipiodol flushing is an effective treatment for couples with unexplained infertility (based on meta-analysis data), but is particularly effective for women with endometriosis who have normal Fallopian tubes and ovaries.     

A randomized trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13-20 weeks gestation

BACKGROUND: Several studies have now reported the successful use of the sublingual administration of misoprostol for medical abortion in the first trimester. The objective of this study was to assess the acceptability to women, the efficacy of the regimen, as well as the acceptability to staff of sublingual versus vaginal administration of misoprostol following mifepristone for medical abortion at 13-20 weeks gestation. METHODS: Women were randomized by opening consecutive sealed envelopes generated using random number tables. Mifepristone (200 mg) was followed 36-48 h later by sublingual administration of misoprostol 600 microg or vaginal misoprostol 800 microg. This was followed by 3 hourly doses of misoprostol 400 microg administered sublingually or vaginally. RESULTS: A total of 76 women were randomized. Of women in the sublingual group, 24 (66.7%) expressed satisfaction with the route of misoprostol administration compared with 25 (62.5%) in the vaginal group. A higher proportion in the sublingual group used intramuscular opiates. There was no significant difference in the surgical evacuation rate between the sublingual (three out of 36 women, 8.3%) and vaginal groups (one out of 40, 2.5%), (P=0.26) and acceptability to staff was the same for both methods. CONCLUSIONS: Sublingual administration of misoprostol following mifepristone is an acceptable and effective alternative to vaginal administration for medical abortion at 13-20 weeks gestation. However, women should be advised about the greater likelihood of requiring stronger analgesia.