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PubMedDate not supplied

Medical management of ectopic pregnancy--the role of methotrexate.

Ectopic pregnancy is an increasing health risk for women throughout the world. Recent advances in measurements of serum quantitative beta human chorionic gonadotropin and transvaginal ultrasonography have made it possible to diagnose ectopic pregnancy without laparoscopy. These developments have provided the atmosphere for trials using methotrexate as a nonsurgical treatment for ectopic pregnancy. This article briefly reviews the epidemiology and diagnosis of ectopic pregnancy. The medical management of ectopic pregnancy with methotrexate is then reviewed in more detail.

Chorionic Gonadotropin↗
PubMed1994

Failure of standard criteria to diagnose nonemergency ectopic pregnancies in a noninfertility patient population.

Algorithms for the diagnosis of ectopic pregnancy are applied independent of the patient population. However, patients may require care at various times of gestation or for different reasons. To examine the utility of the same diagnostic criteria for identifying an ectopic pregnancy in different patient populations, we evaluated women from the infertility clinic and the residents' gynecology clinic at Yale-New Haven Hospital. Sixty women with nonemergency ectopic pregnancies were identified, 38 from the infertility clinic and 22 from the residents' clinic. Although the most common symptoms were the same in both groups (abdominal pain, spotting/bleeding >3 days, dizziness, shoulder pain), they were significantly more frequent in women form the residents' clinic. Despite care by the same attending physicians, ruptured ectopic pregnancies were more than 3 times as likely to occur in the noninfertility patients, and half as likely to be treated laparoscopically (p<0.01). Patients from the residents' clinic also were more likely to have postoperative complications (p<0.5), and had over a threefold higher risk of receiving a blood transfusion. We conclude that criteria for diagnosis and intervention in ectopic pregnancy may have to be modified on the basis of characteristics of the patient population.

Abdominal Pain↗
PubMed1999

Cushing's syndrome secondary to ectopic ACTH secretion from metastatic breast carcinoma.

Breast carcinoma is a rare cause of ectopic ACTH syndrome. There are only two previously reported cases in which ACTH secretion is documented. We describe the case of a 56-year-old woman who presented with clinical and biochemical features of ectopic ACTH syndrome in the setting of metastatic breast carcinoma. Despite aggressive management of her ectopic ACTH syndrome, her course was complicated by opportunistic infection, respiratory failure and death. Immunostaining of the breast metastases for ACTH was positive and in situ hybridization revealed proopiomelanocortin gene expression. This is the first reported case of ectopic ACTH syndrome associated with metastatic breast cancer in which the technique of in situ hybridization has been used to confirm the breast cancer metastases as the source of ectopic ACTH secretion.

ACTH Syndrome, Ectopic↗
PubMed2001

Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy.

AIMS: Tubal ectopic hydatidiform moles are rare lesions, and only 40 cases have been reported in the world literature. We investigated the apparently high incidence of tubal ectopic hydatidiform moles in women referred for treatment to a Supraregional Trophoblastic Tumour Screening and Treatment Centre between 1986 and 1996. METHODS AND RESULTS: Of 4261 women referred during the study period, 25 (0.6%) had a suspected tubal ectopic hydatidiform mole and paraffin-embedded tissue was available in 20 (80%) of these. Each case was reviewed by two pathologists and DNA flow cytometric analysis was undertaken when the histological diagnosis was initially deemed equivocal or suggestive of hydatidiform mole. On review, 17 cases (85%) showed no evidence of hydatidiform mole (circumferential trophoblastic proliferation, hydrops, scalloped villi, and stromal karyorrhexis). Of these, 11 cases (65%) showed features of early placentation and six (35%) showed hydropic abortion. DNA flow cytometry was performed in 14 (82%) of these cases and revealed a diploid population in each case. Three cases of molar pregnancy (15%) were identified. Each of these cases had the histological features of an early complete hydatidiform mole. Sufficient tissue was available for DNA flow cytometric analysis in two of these cases and confirmed the presence of diploidy in each. CONCLUSION: Our results show that tubal ectopic hydatidiform mole is a rare entity and demonstrate that it is over-diagnosed. Polar trophoblastic proliferation and hydropic villi are features of early placentation and of hydropic abortion. Sheets of extravillous trophoblast may be particularly prominent in tubal ectopic gestation. In the absence of circumferential trophoblastic proliferation combined with hydropic change a diagnosis of gestational trophoblastic disease should be avoided.

Abortion, Spontaneous↗
PubMed2002

Progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate.

The objective of this study was to evaluate a progesterone cutpoint of 5.0 ng/mL ability to identify abnormal pregnancy (abnormal intrauterine pregnancy and ectopic pregnancy) as well as ectopic pregnancy alone in 2 subclasses of indeterminate ultrasounds. This was a prospective observational study of emergency department patients with abdominal pain or vaginal bleeding and an indeterminate transvaginal ultrasound. Two subclasses of indeterminate ultrasounds were eligible: those with an empty uterus and a beta-human chorionic gonadotropin value <3,000 mIU/mL and those with a nonspecific fluid collection. Patients were enrolled if a progesterone assay was collected the day of the emergency department visit. Patients were excluded if lost to follow-up. One hundred sixty patients were enrolled. Of these, 24 were diagnosed with ectopic pregnancy. The sensitivity and specificity of progesterone identifying abnormal pregnancy were 84% and 97%, respectively. The sensitivity and specificity of progesterone identifying ectopic pregnancy were 88% and 40%, respectively. In the 2 subclasses, the progesterone cutpoint was both sensitive and specific in identifying abnormal pregnancy and was sensitive but only moderately specific for identifying ectopic pregnancy.

Abdominal Pain↗
PubMed2001

Androgen secretion in ectopic ACTH syndrome and in Cushing's disease: modifications before and after surgery.

The role of ACTH in the control of adrenal androgen secretion is known, although the possible existence of other regulatory factors has been also suggested. While some data concerning Cushing's disease have been reported, only few studies concerned androgen levels in ectopic ACTH secretion. The aim of this study was to evaluate serum DHEA-S, androstenedione (A) and testosterone (T) levels in 36 women with ACTH-dependent Cushing's syndrome (30 with Cushing's disease and 6 with ectopic ACTH secretion) before and after surgery. Two men with ectopic ACTH production were also studied. In 30 women with Cushing's disease serum DHEA-S (9.6 +/- 0.9 micromol/l), A (15.2 +/- 1.2 nmol/l) and T (4.1 +/- 0.5 nmol/l) were higher than in controls (p < 0.01): elevated DHEA-S, A and T values were found in 8, 18 and 17 cases, respectively. After adenomectomy in 15 apparently cured patients DHEA-S, A and T levels were low at 1 - 3 months and at 6 - 12 months after surgery. At 18 - 24 months, DHEA-S remained low in spite of cortisol normalisation. In ectopic Cushing's syndrome, A levels were significantly higher (23.1 +/- 4.9 nmol/l) than in Cushing's disease (p < 0.05), while no differences were found in DHEA-S and T levels. Two patients had elevated DHEA-S values, 3 women had high T levels and 7 of the 8 patients had very high A concentration that was lowered in 3 operated cases. In conclusion, the pattern of adrenal androgen secretion is rather different in patients with pituitary or with ectopic Cushing's syndrome. While the frequency of DHEA-S and T alterations is similar, androstenedione secretion is greatly increased in the latter condition. It is suggested that in ACTH-secreting non-pituitary tumours, the production of a POMC-derived peptide, although unidentified, may lead to preferentially stimulated androstenedione secretion, without affecting other enzymatic pathways.

ACTH Syndrome, Ectopic↗
PubMed2000

Serum progesterone testing to predict ectopic pregnancy in symptomatic first-trimester patients.

STUDY OBJECTIVE: This study was conducted to prospectively measure the accuracy of serum progesterone levels to detect ectopic pregnancy. METHODS: Seven hundred sixteen symptomatic first-trimester emergency department patients with abdominal pain or vaginal bleeding at a tertiary care military teaching hospital had progesterone levels measured by radioimmunoassay with results unavailable to the treating physician. All patients were monitored until a criterion standard diagnosis of intrauterine pregnancy or ectopic pregnancy was confirmed. RESULTS: A 14-month derivation phase (n=399) used receiver operating characteristic curve testing to select a cutoff value of progesterone less than 22 ng/mL. A 12-month validation phase (n=317) then retested this cutoff value. Combining both phases, there were 434 (61%) viable intrauterine pregnancies, 229 (32%) nonviable intrauterine pregnancies, and 52 (7. 3%) ectopic pregnancies, of which 17 were ruptured. Sensitivity, specificity, positive predictive values, and negative predictive values (95% confidence intervals) for progesterone levels less than 22 ng/mL to detect ectopic pregnancy were 100% (94% to 100%), 27% (23% to 30%), 10% (7% to 12%), and 100% (98% to 100%), respectively. CONCLUSION: Given similar disease prevalence, roughly one fourth (178/716) of symptomatic patients can be classified as low risk (0%, 95% confidence interval 0 to 2%) for having an ectopic pregnancy using a progesterone cutoff of 22 ng/mL. Whether implementation of rapid progesterone testing can safely expedite care and reduce the need for urgent diagnostic evaluation or admission remains to be determined.

Abdominal Pain↗
PubMed2002

Management of ectopic pregnancy in a Scottish teaching hospital: implications for training.

An audit was undertaken to assess the management of 50 consecutive women with an ectopic pregnancy at a teaching hospital in Scotland. The ectopic pregnancy was removed laparoscopically in 62% and of these women 80% were discharged home on the first postoperative day. In a minority of patients, elements of substandard care were identified including failure to operate when the ectopic pregnancy had been visualised on ultrasound or in the presence of static hCG levels in patients with an empty uterus and adnexal pain. Fewer than 50% of consultants and no junior registrar reported competency in the laparoscopic management of these patients. We suggest that the management of ectopic pregnancy could be improved by following published algorithms with high diagnostic accuracy. In addition, either skilled endoscopic teams should be developed to take on the responsibility of the management of these patients or universal consultant competency in laparascopic surgery is required if we are to offer laparoscopy to all women with ectopic pregnancy.

Adolescent↗
PubMed2003

The impact of ectopic pregnancy: a 16-year follow-up study.

Ectopic pregnancy is a potentially life-threatening event that represents the loss of a pregnancy and also may have longer-term consequences for fertility. Despite this triple threat to a woman's well-being, almost no systematic research exists on the psychological impact of ectopic pregnancy. We sought to reinterview 18 women who had been interviewed 2 months following an ectopic pregnancy as part of a longitudinal study of pregnancy loss 16 years previously. Thirteen of these women responded to questions about the long-term impact of the ectopic pregnancy on their lives in the intervening years. For many of the women, the ectopic pregnancy was a traumatic experience that impaired their fertility, strained their marriages, and led to a crisis of faith. Yet, despite the trauma of the event, overall the women found ways to interpret it positively and to use it as a source of meaning in their lives.

Adaptation, Psychological↗
PubMed2005

Ectopic pregnancy with postcoital contraception--a case report.

The incidence of ectopic pregnancies is increasing. Common risk factors are tubal pathology, previous tubal surgery, previous ectopic pregnancy, intrauterine device use and embryo transfer. Levonelle-2, a progesterone-only postcoital contraceptive works by a combination of mechanisms including ovulation inhibition, prevention of fertilization, and inhibition of implantation. It is 85% effective and there have been 12 reported cases of ectopic pregnancy in the UK with its use. It is believed that progesterone slows the intratubal migration of the fertilized ovum. In the case reported here, a woman presented with an ectopic pregnancy after use of Levonelle-2 as postcoital contraception; there were no clinical predisposing risk factors. In the absence of any histological evidence of tubal damage, we suspect that the levonorgestrel from Levonelle-2 could have been responsible for delayed embryo transfer which resulted in the ectopic pregnancy.

Adult↗
PubMed1999

Ectopic eruption of the maxillary canine quantified in three dimensions on cephalometric radiographs between the ages of 5 and 15 years.

The eruption paths of 20 ectopic maxillary canine teeth (10 right, 10 left) were measured in three dimensions on annual lateral and depressed postero-anterior cephalometric radiographs of 15 patients between the ages of 5 and 15 years and compared with the eruption of normal canines. It was found that between the ages of 8 and 12 years ectopic canines on the left side moved more anteriorly than the normally erupting canines and the same was true of the right canines between the ages of 7 and 12 years. While the ectopic canines moved occlusally, their vertical movement was less than normal which accounts for the clinical finding that canines are impacted in the palate at a high level. The average palatally ectopic canine always moves palatally, and never shares in the buccal movement shown by normally erupting canines between the ages of 10 and 12 years. It was interesting to find that the differences between growth of normal and ectopic canines in the lateral plane of space are present as early as 5-6 years.

Adolescent↗
PubMed1998

Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility.

Methotrexate treatment was compared to laparoscopic salpingotomy for conservative management of ectopic pregnancy in a prospective randomized study. One hundred patients were randomized into two groups using random numbers. Inclusion criteria were an ectopic pregnancy visualized by ultrasound with a pre-therapeutic score <13 as assessed by the following six criteria, graded from 1 to 3: gestational age, human chorionic gonadotrophin (HCG) concentration, progesterone concentration, abdominal pain, haemoperitoneal volume and diameter of the haematosalpinx. The treatments were either 1 mg/kg of methotrexate injected transvaginally into the ectopic pregnancy without anaesthesia or administered i.m. when the pregnancy could not safely or easily be punctured (group 1), or laparoscopic salpingotomy (group 2). Success was defined as the return to normal (<10 mIU/ml) of HCG concentrations. Treatment was successful for 45 of 51 patients in group 1 (88.2%) and 47 of 49 in group 2 (95.9%). Medical treatment was significantly (P < 0.05) associated with shorter postoperative stay (24 compared with 46 h), but HCG returned to normal more quickly after laparoscopic treatment (13 compared with 29 days). Spontaneous reproductive performance was similar in both groups, but overall intrauterine pregnancy was higher, and repeat ectopic pregnancy lower, after methotrexate treatment. In selected cases of ectopic pregnancy, with a pre-therapeutic score <13, methotrexate treatment appeared as safe and efficient as conservative treatment by laparoscopy and was associated with improved subsequent fertility.

Adolescent↗
PubMed1998

Serological responses of patients with ectopic pregnancy to epitopes of the Chlamydia trachomatis 60 kDa heat shock protein.

Clinical and histopathological correlations of immunoreactivity to Chlamydia trachomatis and to epitopes of the C. trachomatis 60 kDa heat shock protein (hsp60) among women with ectopic pregnancy were evaluated in a case-control study. Serological responses to 13 synthetic peptides corresponding to major epitopes of the chlamydial hsp60 were determined in 67 women treated for ectopic pregnancy and 45 women with uncomplicated pregnancy in utero. Plasma cell salpingitis was detected in 29 (43.3%) of the ectopic patients. Its presence correlated with antibodies to two hsp60 epitopes, encompassing amino acids 260-271 and 411-422 (P = 0.02). Antibodies to these two epitopes, along with five other epitopes, also correlated with peritubal adhesion formation in ectopic pregnant patients (P < 0.01). Antibodies to epitopes 260-271 and 188-199 also correlated with a history of pelvic inflammatory disease (PID; P = 0.05). Patients with ectopic pregnancy were also more likely than their intrauterine pregnant controls to have present anti-chlamydial immunoglobulin G (P < 0.005). Women positive for both C. trachomatis and hsp60 epitope antibodies had an increased prevalence over controls of salpingitis, pelvic adhesions or history of PID (P < 0.05). In contrast, patients who were positive for only C. trachomatis antibodies or only hsp60 epitope antibodies did not differ from antibody-negative patients in each of these categories.

Adult↗
PubMed2002

Tubal ectopic pregnancy: a patho-physiological explanation involving endometriosis.

The condition of tubal ectopic pregnancy is presented from diverse points of view, bringing out physiological explanations for its occurrence in primates and striking absence in other mammals. Part of the flexibility underlying ectopic pregnancy in humans stems from the absence of a uterine luteolytic mechanism, enabling early embryonic development in the Fallopian tube without compromising function of the corpus luteum. Attention is devoted to a potential overlap between the composition of tubal and uterine fluids, and to specific mixing between the two fluid compartments, expressed in an ability of the human oocyte or zygote to tolerate transplantation to the uterus. Perturbed tubal oocyte transport is seen as a contributory factor, not least as a sequel to episodes of infection and a modified endosalpinx, but the essay then reasons strongly for an involvement of endometriosis in the aetiology of tubal ectopic pregnancy. Proliferation of refluxed endometrial tissue arrested within the Fallopian tube could provide the epithelial characteristics of a uterine environment. Accordingly, an experimental model is proposed for tubal ectopic pregnancy in animals based upon transplants of endometrial tissue and the subsequent introduction of embryos into both the Fallopian tubes and uterus; the latter would suppress the luteolytic mechanism. Finally, advances are suggested based upon molecular scanning of human ectopic tissues and those derived from animal models. If molecular probes could be developed to detect either early tubal pregnancy or a propensity to this pathology, such advances would clearly have clinical relevance-not least in view of an enhanced incidence of tubal pregnancy arising after assisted reproduction technology.

Animals↗
PubMed1987

The influence of secular effects and gravidity on the rate of ectopic pregnancy in a Norwegian population.

In order to assess the influence of secular effects and gravidity on the incidence rate of ectopic pregnancy, information from reproductive history questionnaires was obtained for 7804 gravid females identified through the Norwegian Twin Panel. The overall ectopic pregnancy incidence rate was 5.6 per 1000 estimated conceptions, with rates increasing for women born after 1950. Women experiencing their first pregnancy were at lowest risk for that pregnancy being ectopic. When women were stratified by whether they were born before or after 1950, gravidity still had an effect on the incidence rate of ectopic pregnancy. Conversely, year of birth was influential when stratifying by gravidity. The results obtained here suggest that the recent increase in the incidence of ectopic pregnancy is unrelated to the number of prior pregnancies.

Diseases in Twins↗
PubMed1992

Chlamydia trachomatis-associated ectopic pregnancy: serologic and histologic correlates.

Fifty-five women with ectopic pregnancy and 24 undergoing tubal ligation with a segmental resection of the fallopian tube were evaluated for histopathology of the fallopian tube, Chlamydia trachomatis serum antibodies, antibodies to a chlamydial sarkosyl-soluble 57-kDa protein, and for isolation of C. trachomatis. Plasma cell infiltration in the fallopian tube submucosa was identified in 31 (65%) of 48 women with ectopic pregnancies and in 8 (33%) of 24 undergoing tubal ligation (P = .01; odds ratio [OR], 3.6; 95% confidence interval [CI], 1.3-10.3). Plasma cell infiltration was correlated with C. trachomatis seropositivity among women with ectopic pregnancy (P = .005; OR, 7.2; 95% CI, 1.7-31) and among women undergoing tubal ligation (P = .008). Of 21 C. trachomatis-seropositive women with ectopic pregnancies, 19 had antibodies to the 57-kDa antigen compared with 1 of 4 seropositive women having tubal ligation (P = .008). Immune responses to the 57-kDa antigen may be involved in the immunopathogenesis of C. trachomatis-associated ectopic pregnancy.

Adolescent↗
PubMed1982

Induced abortion and ectopic pregnancy in subsequent pregnancies.

In a prospective study the rate of ectopic pregnancies of women with prior induced abortion was contrasted to two sets of comparison groups: a large set of unmatched observations and a smaller subset of matched and refined data. The crude rates of ectopic pregnancy among 4004 abortion and 98,316 control pregnancies, excluding repeat pregnancies of the same women, were 0.57% and 0.49%, respectively. No significant association was detected between history of induced abortion and ectopic pregnancy based on the chi 2 analysis on unmatched data stratified by maternal age and marital status (relative risk = 1.18, 95% confidence limits (CL) 0.57-1.79) or the multivariate logistic regression analysis on the smaller set of data (relative risk = 1.34, 95% CL 0.66-2.72). Within pregnancies of the induced abortion group the risk of ectopic pregnancy was not related to abortion procedure, use of laminaria, number of prior induced abortions, or length of gestation at time of abortion. However, there was a clear association between the presence of post-abortion infection or retained secundines and ectopic pregnancy with a fivefold increase for those pregnancies of women with a history of these complications over those without these complications within the induced abortion cohort.

Abortion, Induced↗
PubMed1995

Local injection of methotrexate dissolved in saline versus methotrexate suspensions for the conservative treatment of ectopic pregnancy.

To compare the local injection of methotrexate (MTX) dissolved in saline and MTX suspensions for the laparoscopic treatment of ectopic pregnancy in terms of success rate and postoperative tubal patency. A total of 26 patients with unruptured ectopic pregnancies were selected from among 60 women with ectopic pregnancies admitted to the Nagasaki University clinic. Of these patients, 12 were treated with MTX dissolved in saline solution (solution group) and 14 with MTX suspensions consisting of lipiodol (LPD) with phosphatidylcholine (PC) added as a dispersing stabilizer (suspension group). Except for one case treated under transvaginal guidance, all the patients were treated by laparoscopy. Persistent ectopic pregnancy was recognized in seven cases (58%) in the solution group but in only two cases (14%) in the suspension group. Moreover, rupture occurred in two cases in the solution group but in no case in the suspension group. A patent treated tube was found in seven of 10 cases in the saline group and in 10 of 12 cases in the suspension group. During the follow-up period of 6-31 months, five women in the saline group and three women in the suspension group had an intrauterine pregnancy. In this study, the local injection of MTX is considered to be a reasonable method for the treatment of unruptured ectopic pregnancy, and the MTX suspension seems to be more effective and useful than MTX solution.

Adolescent↗