Gestational Trophoblastic Neoplasia Following Molar Ectopic Pregnancy A Case Report

BACKGROUND: Ectopic molar pregnancy is a gestational trophoblastic disease (GTD) of rare occurrence and therefore not always remembered as a diagnostic possibility.CASE: We describe a case of molar ectopic pregnancy in a primiparous woman who developed gestational trophoblastic neoplasia and required chemotherapy to achieve remission.CONCLUSION This case stresses the important role of histopathologic examination in establishing a diagnosis of ectopic molar pregnancy. Moreover, close follow-up of human chorionic gonadotropin levels is required when a GTD is suspected. (J Reprod Med 2008;53:579-582)

Tubal damage, infertility and tubal ectopic pregnancy : chlamydia trachomatis and other microbial aetiologies

Infertility is a worldwide health problem with one in six couples suffering from this condition and with a major economic burden on the global healthcare industry. Estimates of the current global infertility rate suggest that 15% of couples are infertile (Zegers-Hochschild et al 2009) defined as: (1) failure to conceive after 12 months of unprotected sexual intercourse (i.e. infertility); (2) repeated implantation failure following ART cycles; or (3) recurrent miscarriage without difficulty conceiving (natural conceptions). Tubal factor infertility is among the leading causes of female factor infertility accounting for 7-9.8% of all female factor infertilities. Tubal disease directly causes from 36% to 85% of all cases of female factor infertility in developed and developing nations respectively and is associated with polymicrobial aetiologies. One of the leading global causes of tubal factor infertility is thought to be symptomatic (and asymptomatic in up to 70% cases) infection of the female reproductive tract with the sexually transmitted pathogen, Chlamydia trachomatis. Infection-related damage to the Fallopian tubes caused by Chlamydia accounts for more than 70% of cases of infertility in women from developing nations such as sub-Saharan Africa (Sharma et al 2009). Bacterial vaginosis, a condition associated with increased transmission of sexually transmitted infections including those caused by Neisseria gonorrhoeae and Mycoplasma genitalium is present in two thirds of women with pelvic inflammatory disease (PID). This review will focus on (1) the polymicrobial aetiologies of tubal factor infertility and (2) studies involved in screening for, and treatment and control of, Chlamydial infection to prevent PID and the associated sequelae of Fallopian tube inflammation that may lead to infertility and ectopic pregnancy.

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery.

Hydatidiform Mole in Ectopic Pregnancy Clinical, Imaging, Pathological and Immunohistochemical Characteristics

OBJECTIVE: To determine the clinical, pathological, immunohistochemical and imaging characteristics of hydatidiform mole in ectopic pregnancy (HMEP) in all the cases admitted to the Department of Obstetrics and Gynecology, University Hospital of Caracas (HUC), Central University of Venezuela.STUDY DESIGN: Retrospective and comparative study, based on clinical records review of 2 groups: 10 cases with a diagnosis of HMEP and 20 cases with intrauterine hydatidiform mole (IUHM) admitted to the Obstetrics and Gynecology Department of HUC from 1996 to 2010. Clinical, pathological, immunohistochemical and imaging features were analyzed.RESULTS: The prevalence of HMEP in this study was 0.14:1,000 pregnancies; in this group the mean age was 28.8 years, and the mean gestational age at admission was 8.6 weeks. Both groups (HMEP and IUHM) were comparable in these last variables. Abdominal pain and genital bleeding were the most common clinical symptoms in the HMEP group, while it was vaginal bleeding in the IUHM group. Ultrasound findings were similar to those traditionally described in nonmolar ectopic pregnancy. Histology and immunohistochemistry showed that all cases of HMEP were partial mole.CONCLUSION: Although in this study the prevalence of HMEP was high, the size of the sample limits definitive conclusions. This study concludes that all cases of HMEP are partial mole. (J Reprod Med 2012;57:329-332)

Chlamydia infection, pelvic inflammatory disease, ectopic pregnancy and infertility: cross-national study

Objectives To describe, using routine data in selected countries, chlamydia control activities and rates of chlamydia infection, pelvic inflammatory disease (PID), ectopic pregnancy and infertility and to compare trends in chlamydia positivity with rates of PID and ectopic pregnancy. Methods Cross-national comparison including national data from Australia, Denmark, the Netherlands, New Zealand, Sweden and Switzerland. Routine data sources about chlamydia diagnosis and testing and International Classification of Disease-10 coded diagnoses of PID, ectopic pregnancy and infertility in women aged 15–39 years from 1999 to 2008 were described. Trends over time and relevant associations were examined using Poisson regression. Results Opportunistic chlamydia testing was recommended in all countries except Switzerland, but target groups differed. Rates of chlamydia testing were highest in New Zealand. Chlamydia positivity was similar in all countries with available data (Denmark, New Zealand and Sweden) and increased over time. Increasing chlamydia positivity rates were associated with decreasing PID rates in Denmark and Sweden and with decreasing ectopic pregnancy rates in Denmark, New Zealand and Sweden. Ectopic pregnancy rates appeared to increase over time in 15–19-year-olds in several countries. Trends in infertility diagnoses were very variable. Conclusions The intensity of recommendations about chlamydia control varied between countries but was not consistently related to levels of chlamydia diagnosis or testing. Relationships between levels of chlamydia infection and complication rates between or within countries over time were not straightforward. Development and validation of indicators of chlamydia-related morbidity that can be compared across countries and over time should be pursued.

A CASE-CONTROL STUDY OF RISK FACTORS FOR ECTOPIC PREGNANCY (ROCHESTER, MINNESOTA, OBSTETRICS)

A population-based case-control study of risk factors for ectopic pregnancy has been conducted. The investigation includes 274 cases diagnosed in Rochester, Minnesota residents from 1935 through 1982, and 548 matched controls selected from live birth deliveries. Risk factor information documented prior to the last index menstrual period was obtained via medical record abstract for 22 potential risk factor variables.^ Univariate matched analyses revealed nine variables with significantly elevated odds ratios (ORs). Following conditional logistic regression for matched sets, four variables remained as significant risk factors for ectopic pregnancy. These risk factors with ORs and 95% confidence intervals (Cls) were: current intrauterine device use (OR = 13.7, Cl = 1.6 - 120.6), infertility (OR = 2.6, Cl = 1.6 - 4.2), pelvic inflammatory disease (OR = 3.3, Cl = 1.6 - 6.6), and tubal surgery (OR = 4.5, Cl = 1.5 - 13.9). After adjusting for these four major risk factors, the following variables did not have statistically significant ORs: abdominal/pelvic surgery (OR = 2.0), acute appendicitis (OR = 2.0), anovulation (OR = 1.2), clomiphene citrate use during the index conception (OR = 3.5), induced abortion (OR = 2.1), in utero exposure to diethylstilbestrol (OR = 1.6), myomas (OR = 0.7), ovarian cysts (OR = 1.0), and past intrauterine device use (OR = 1.2). ^

Screening for chlamydial infections and the risk of ectopic pregnancy in a county in Sweden: ecological analysis

Objectives: To analyse trends in rates of genital chlamydial infection and ectopic pregnancy between 1985 and 1995 in a county in Sweden.

A medical management of interstitial ectopic pregnancy: A 5-year clinical study

Background: Medical treatment of the rare interstitial ectopic pregnancy with methotrexate has been considered an alternative to surgical resection. Aim: To determine the treatment success rate with a single-dose intravenous methotrexate/folinic acid regimen and to identify predictors of treatment outcome. Methods: A 5-year audit (April 2000-August 2005) was carried out, collecting clinical imaging data and serum beta-human chorionic gonadotrophin (beta-hCG). Time taken for complete beta-hCG resolution was recorded, and a negative beta-hCG result was used as an endpoint of successful outcome. Results: Of the 13 cases, two required urgent surgery for rupture on presentation. In the remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic acid rescue (15 mg x 4 doses). There were no side-effects. Complete beta-hCG resolution was achieved in 10 of the 11 medically treated cases (91% success rate), requiring 21-129 days. Successful outcome was seen with initial beta-hCG level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live fetus. Conclusion: The methotrexate/folinic acid regimen used as a one-dose treatment is safe and effective for unruptured interstitial pregnancy, with no side-effects and the advantage of avoiding invasive surgery. Subsequent tubal patency and reproductive function are yet to be ascertained.

Ectopic Pregnancy

Chapter explains the signs and symptoms of Ectopic Pregnancy, investigations and management

Caesarean section and subsequent pregnancy outcome: a Danish register-based cohort study

Background and Aims: Caesarean section rates have increased in recent decades and the effects on subsequent pregnancy outcome are largely unknown. Prior research has hypothesised that Caesarean section delivery may lead to an increased risk of subsequent stillbirth, miscarriage, ectopic pregnancy and sub-fertility. Structure and Methods: Papers 1-3 are systematic reviews with meta-analyses. Papers 4-6 are findings from this thesis on the rate of subsequent stillbirth, miscarriage, ectopic pregnancy and live birth by mode of delivery. Results Systematic reviews and meta-analyses: A 23% increased odds of subsequent stillbirth; no increase in odds of subsequent ectopic pregnancy and a 10% reduction in the odds of subsequent live birth among women with a previous Caesarean section were found in the various meta-analyses. Danish cohorts: Results from the Danish Civil Registration System (CRS) cohort revealed a small increased rate of subsequent stillbirth and ectopic pregnancy among women with a primary Caesarean section, which remained in the analyses by type of Caesarean. No increased rate of miscarriage was found among women with a primary Caesarean section. In the CRS data, women with a primary Caesarean section had a significantly reduced rate of subsequent live birth particularly among women with primary elective and maternal-requested Caesarean sections. In the Aarhus Birth Cohort, overall the effect of mode of delivery on the rate and time to next live birth was minimal. Conclusions: Primary Caesarean section was associated with a small increased rate of stillbirth and ectopic pregnancy, which may be in part due to underlying medical conditions. No increased rate of miscarriage was found. A reduced rate of subsequent live birth was found among Caesarean section in the CRS data. In the smaller ABC cohort, a small reduction in rate of subsequent live birth was found among women with a primary Caesarean section and is most likely due to maternal choice rather than any ill effects of the Caesarean. The findings of this study, the largest and most comprehensive to date will be of significant interest to health care providers and women globally.

Video laparoscopic intervention for an interstitial pregnancy after failure of clinical treatment

CONTEXT: Interstitial pregnancy is a rare form of ectopic pregnancy for which the best therapeutic course of action has yet to be determined. Surgical intervention entails a high risk of hemorrhage due to the great vascularization of the cornual region of the uterus. Case descriptions facilitate the analysis of results and aid clinicians in determining the most appropriate course of action in these situations. CASE REPORT: In a patient with an ultrasound diagnosis of interstitial pregnancy, clinical treatment using methotrexate was chosen. However, after one week, there was a marked decline in the serum level of the β subunit of chorionic gonadotropin hormone, although an ultrasound examination revealed embryonic cardiac activity. A second dose of the chemotherapy was administered. Embryonic cardiac activity persisted 48 hours later. Video laparoscopy was performed to achieve right-side cornual resection, which resulted in satisfactory resolution of the case.

A comparison of the effects of a chlamydial vaccine administered during or after a C. muridarum urogenital infection of female mice

There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

Fertility and infertility : studies in reproductive epidemiology in Australia

Worldwide, there are few large-scale epidemiological studies on infertility. In Australia, population-based research on infertility is limited to a few small-scale studies. Therefore, the prevalence of infertility and unmet need for specialist medical advice and treatment cannot be estimated reliably. Women who have used assisted reproductive technologies (ART) are recorded in treatment registries. However, there are many infertile women who are excluded from these clinical populations because they neither seek advice nor use treatment. The thesis was based on a biopsychosocial model of health and used the methods of reproductive epidemiology to address the lack of national data on the prevalence of infertility in Australia. Firstly, numbers of births and pregnancy losses were investigated in two generations of women participating in the Australian Longitudinal Study on Women’s Health (ALSWH). The ALSWH is a broad-ranging, longitudinal examination of biological, psychological and social factors that impact on women’s health and wellbeing. Women from three age cohorts were randomly sampled from the population using the universal public health insurance (i.e., Medicare) database and ALSWH participants were representative of the female population. However, the studies in the thesis only involved data from two cohorts. The younger cohort were born in 1973-78 and completed up to four mailed surveys between 1996 (when they were aged 18-23 years, n=14247) and 2006 (28-33 years, n=9145). The mid-aged cohort were born in 1946-51 and completed four mailed surveys between 1996 (when they were aged 45-50 years n=13715) and 2004 (53-58 years, n=10905). Compared to other studies that focus on outcomes of single pregnancies, these studies included all pregnancy outcomes by developing comprehensive reproductive histories for each woman. Pregnancy outcomes included birth, miscarriage, stillbirth, termination and ectopic pregnancy. Women in the youngest cohort (born in 1973-78) were only just reaching their peak childbearing years and many (44%) had yet to report their first pregnancy outcome. Women from the mid-aged cohort (born 1946-51) had completed their reproductive lives and 92% were able to report on their lifetime pregnancy outcomes. Pregnancy losses, especially miscarriage, were common for both generations of women. Secondly, the prevalence of infertility, seeking medical advice and using treatment was identified for these two generations of women. For the older generation, the lifetime prevalence of infertility and demand for treatment was investigated in the context of the specialist medical services which became available circa 1980. By this time, however, most of these older women had already been pregnant and completed their families. For women who experienced infertility (11%), their options for advice and treatment were limited and less than half (42%) had used any treatment. More recently for the younger generation of women, who were aged 28-33 years in 2006, specialist advice and treatment were extensively available. Among women who had tried to conceive or had been pregnant (n=5936), 17% had experienced infertility and the majority (72%) were able to access medical advice. However, after seeking advice only half of these infertile women had used treatment with fertility hormones or in vitro fertilisation (IVF). Overall for infertile women aged up to 33 years, only one-third had used these treatments. Thirdly, the barriers to accessing medical advice and using treatment for infertility were identified for women aged less than 34 years. Among a community sample of infertile women aged 28-33 years (ALSWH participants), self-reported depression was found to be a barrier to accessing medical advice. The characteristics of these infertile women in the community who had (n=121) or had not (n=110) used treatment were compared to infertile women aged 27-33 years (n=59) attending four fertility clinics. Compared to infertile women in the community, living in major cities and having private health insurance were associated with early use of treatment for infertility at specialist clinics by women aged <34 years. In contrast to most clinical studies of IVF, the final study reported in the thesis took into account repeated IVF cycles and the impact of women’s individual histories on IVF outcomes. Among 121 infertile women (aged 27-46 years) who had 286 IVF cycles, older age and prolonged use of the oral contraceptive pill were associated with fewer eggs collected. Further, women in particular occupations had lower proportions of eggs fertilised normally than women in other occupational groups. These studies form the first large-scale epidemiological examination of infertility in Australia. The finding that two-thirds of women with infertility had not used treatment indicates that there is an unmet need for specialist treatment in women aged less than 34 years. However, barriers to accessing treatment prevent women using ART at a younger age when there is a higher chance of pregnancy.

Human and pathogen factors associated with chlamydia trachomatis-related infertility in women

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.