Ectopic Pregnancy Group Research Articles

The impact of adverse pregnancy events in the initial cycle on subsequent pregnancy outcomes.

Evidence is accumulating on the impact of previous adverse pregnancy events on future fertility in natural conceptions. However, there is limited knowledge on whether an ectopic pregnancy (EP) or miscarriage after an initial in vitro fertilization (IVF) cycle affects the subsequent outcomes. To investigate the effect of first IVF outcomes: miscarriage, EP, and no pregnancy, on the second cycle outcomes based on a freeze-all strategy. Retrospective cohort study. University-affiliated IVF center. This study involved 16,479 women who had undergone 2 complete frozen embryo transfers (FET) and were classified into 3 groups based on first FET outcomes. None. Live birth rate (LBR). After correcting for confounders, the LBR after the second FET was similar between women who suffered an EP and those who had no pregnancies in their first FET cycles (adjusted OR (aOR), 1.03; 95% confidence interval (CI), 0.83-1.28). However, women who experienced a miscarriage versus those with no prior pregnancy in the first FET had significantly higher LBR in their second cycles (aOR, 1.33; 95% CI, 1.20-1.48). The LBR after the second FET was comparable between the previous EP and miscarriage groups (aOR, 1.24; 95% CI, 0.98-1.58). Similar results were found in the propensity score matching models, supporting the robustness of the main findings. Women who had a miscarriage in the first FET cycle had a higher chance of achieving live births in the subsequent treatment cycle when compared to those who had no pregnancy in the initial cycle. Furthermore, it was found that an EP resulting from the first treatment cycle did not negatively impact reproductive outcomes in the next FET cycles.

Salpingectomy for ectopic pregnancy reduces ovarian cancer risk-a nationwide study.

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Ectopic Pregnancy History as an Independent Factor Associated with Recurring Ectopic Pregnancy in Women with Bilateral Salpingectomies. A Matched-Pair Study of IVF Patients

Background: The incidence of ectopic pregnancy (EP) is purportedly elevated among individuals with a history of EP (referred to as the EP group) compared to those with no previous ectopic pregnancy (non-EP group). Nevertheless, the question of whether an EP history represents an autonomous risk factor for subsequent ectopic pregnancy of in vitro fertilization-embryo transfer (IVF-ET) patients remains a subject of debate. Methods: This study is a retrospective cohort study conducted at a single center. A total of sixty-seven patients with a prior ectopic pregnancy (EP) who underwent bilateral salpingectomy were included, and they were age-matched with a control group of 201 patients who did not have a history of EP but underwent bilateral salpingectomy during the period from January 2011 to April 2017. In all cases, laparoscopic salpingectomy was performed, followed by subsequent IVF-ET and frozen-thawed embryo transfer (FET) cycles. Results: The cumulative clinical pregnancy rates in the EP group and non-EP group were 65.7% and 73.6%, respectively, demonstrating no significant difference. Likewise, the cumulative live birth rates between the two groups were comparable (50.7% in the EP group vs. 63.6% in the non-EP group, p = 0.2). However, the incidence of ectopic pregnancy was significantly higher in the EP group compared to the non-EP group (15.9% vs. 3.4%, p = 0.003). Subsequent regression analyses revealed a significant association between a history of EP and an elevated risk of ectopic pregnancy. Conclusions: Women with a history of ectopic pregnancy even if they have had bilateral salpingectomies are at a significantly higher risk of subsequent ectopic pregnancies, indicating that a prior ectopic pregnancy is an independent risk factor for this condition, even if fallopian tubes have been removed.

Long-term follow up of fecundability after ectopic pregnancy in Taiwan: a nationwide population-based study.

Ectopic pregnancy (EP) occurs when a fertilized ovum is implanted outside the uterine cavity. Its incidence is 2% of all pregnancies and is known to decrease fertility. This study aimed to measure pregnancy rates after EP, identify the various parameters influencing pregnancy, and compare these variables in women with and without a history of EP, as well as determine in which medical facilities women with EP seek medical help. The data was extracted from the National Health Insurance Research Database during 2000-2013. The study group included of women with a history of one EP (study group) and women without EP (control group). The chi-square/Fisher exact test was performed for categorical variables, and t-tests were used for continuous variables. The EP group had a higher cumulative pregnancy rate (41.55%) than the control group (37.14 %), and a 1.16 times higher rate in developing pregnancy (p < 0.001). While the pregnancy rate in the EP group was initially lower than in the control group during the first 5 years, it surpassed the control group's rate between the 10 th and 14 th years. Fecundability after EP was lower at the beginning but increased at long-term follow-up.

Predictive value of endometrial receptivity evaluated by three-dimensional ultrasound in ectopic pregnancy after in vitro fertilization-embryo transfer.

The aim of this study was to use three-dimensional (3D) ultrasound to detect ultrasound parameters related to the uterine artery and endometrium, evaluate endometrial receptivity, and investigate the predictive value of each parameter for ectopic pregnancy (EP) after in vitro fertilization-embryo transfer (IVF-ET). Fifty-seven cases of pregnancy following IVF-ET in our institution were collected and split into EP and intrauterine pregnancy (IP) groups based on the location of pregnancy, with 27 cases in EP and 30 cases in IP. Endometrial thickness, type, volume, endometrial blood flow parameters, and uterine artery blood flow parameters were all measured one day before transplantation in both groups, and the differences between the two groups were examined. There were differences in endometrial blood flow typing between the two groups, with type III endometrium accounting for the highest proportion in both; the uterine spiral artery pulsatility index PI was significantly higher in the EP group than in the IP group; there were no statistical differences in uterine volume, uterine artery resistance index mRI, or uterine artery resistance index S/D between the two groups; there were no statistical differences in uterine volume, or uterine artery. Intracavitary 3D ultrasound can assess endometrial tolerance and may predict pregnancy outcome after IVF-ET.

Hydrosalpingeal fluid leads to subfertility via endometrial TNF-α and IL-7 and NF-κB signaling pathways.

To determine the concentrations of the nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-7 (IL-7) in midluteal phase endometrial samples of infertile patients diagnosed with uni or bilateral hydrosalpinx (HX). A total of 24 patients who decided to undergo laparoscopic salpingectomy were included in the study. Salpingectomy indications consisted of patients with a diagnosis of hydrosalpinx (n=12) or ectopic pregnancy (n=12). Twelve healthy patients who underwent Pomeroy-type tubal ligation were considered as the second and healthy control group. The diagnosis of hydrosalpinges was made by transvaginal 2D ultrasonography or HSG. All patients in the hydrosalpinges or ectopic pregnancy group underwent laparoscopic salpingectomy. Just before salpingectomy, endometrial samples were obtained from all patients by Pipelle cannula. Endometrial sampling was performed 7-9 days after the LH surge in the control group. IL-7, NF-κB and TNF-α concentrations were measured by ELISA method in the endometrial samples of all three groups. The endometrial IL-7 concentration before salpingectomy of the patients in the hydrosalpinx group was 44.6±6.65 ng/mg wet-tissue. The IL-7 levels of the HX group were significantly higher than those of the patients in the ectopic pregnancy group (19.3±3.06 ng/mg wet tissue versus 44.6±6.65 ng/mg wet tissue, p<0.04). Similarly, IL-7 levels of the HX group were significantly higher than those of the tubal ligation group (6.08±1.48 ng/mg wet tissue versus 44.6±6.65 ng/mg wet tissue, p<0.03). The endometrial TNF-α concentration of the patients in the hydrosalpinx group was 33.20±5.40 ng/mg wet-tissue. The TNF-α value detected in the hydrosalpinx group was significantly higher than both the TNF-α value in the ectopic pregnancy group (11.8±1.07 ng/mg wet-tissue vs. 33.20±5.40 ng/mg wet-tissue, p<0.01) and the TNF-α value in the tubal ligation group (5.30±1.22 ng/mg wet-tissue vs. 33.20±5.40 ng/mg wet-tissue, p<0.01). The pre-salpingectomy endometrial NF-κB concentration of the patients in the hydrosalpinx group was 6.38±1.40 ng/mg wet-tissue. This value is higher than endometrial NF-κB levels in the ectopic pregnancy group (3.67±0.41 ng/mg wet-tissue vs. 6.38±1.40 ng/mg wet-tissue, p<0.02) and NF-κB levels in the tubal ligation group (1.07±0.38 ng/mg wet-tissue vs. 6.38±1.40 ng/mg wet-tissue, p<0.01). The presence of hydrosalpinx prevents successful implantation by increasing the levels of endometrial proinflammatory cytokines TNF-α, IL-7 and NF-κB.

The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study.

To detect the predictive value of beta human chorionic gonadotropin (β-hCG) levels 16 days post embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology (ART) cycles. In this cross-sectional study, we reviewed the database of Royan Institute from January 2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive β-hCG levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented serum β-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients' files. A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement of β-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for each of the estimates. The mean levels of β-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The β-hCG thresholds predictive of ongoing pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8- 81.7%. However, this relationship was not found in IUI cycles. Based on these findings, if β-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended, until either the diagnosis of EP or miscarriage is established.

Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate.

Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leading to hematoma formation and eventually fallopian tube rupture. Salpingectomy specimens were collected, analysed and divided into three equal groups: patients who received Methotrexate but who ultimately failed medical treatment, patients who had a viable ectopic pregnancy and patients with a self-resolving ectopic pregnancy that were operated due to other medical indications. The specimens were dyed using the Cleaved Caspase-3 (Asp175) Rabbit mA. Specimens were divided into three equal groups and analysed. The patients in self-resolving ectopic pregnancy group were older and had more pregnancies. Rates of apoptosis were found to be less than 1% per slide. Necrosis was not evident in any of the pathological specimens. It seems Methotrexate administration does not lead to a significant tubal necrotic reaction. Further studies are required.

Chlamydia trachomatis infection regulates the expression of tetraspanins, activin-A, and inhibin-A in tubal ectopic pregnancy.

Mechanism of Chlamydia trachomatis causing tubal ectopic pregnancy (EP) is not well understood. Tetraspanins (tspans), activin-A, and inhibin-A might play a role in the development of pathological conditions leading to EP. The study aimed to elucidate the expression of tspans, activin-A, and inhibin-A with a role of associated cytokines in C. trachomatis-associated EP and analyze interacting partners of DEGs, with an expression of a few important interacting genes. Fallopian tissue and serum were collected from 100 EP (Group I) and 100 controls (Group II) from SJH, New Delhi, India. Detection of C. trachomatis was done by polymerase chain reaction (PCR) and IgG antibodies were detected by enzyme-linked immunosorbent assay. Expression of tspans, activin-A, inhibin-A, and cytokines was analyzed by real time (RT)-PCR and their interacting genes were assessed by STRING. Expression of few disease-associated interacting genes was studied by RT-PCR. A total of 29% (Group I) were C. trachomatis positive. Tspans and activin-A were significantly upregulated, while inhibin-A was significantly downregulated in Group Ia. ITGA1, TLR-2, ITGB2, and Smad-3 were a few interacting genes. Expression of ITGA1, TLR-2, and Smad-3 was significantly upregulated in C. trachomatis-positive EP. Results suggested dysregulated tspans, activin-A, and inhibin-A might play a role in C. trachomatis-infected tubal EP.

Evaluation of HSP70 levels in ectopic pregnancy, abortus imminens and intrauterine pregnancy.

Aim: To assess the serum levels of HSP70 concentrations in ectopic pregnancy (EP) patients compared with abortus imminens (AI) patients and healthy controls. Materials & methods: Age-matched patients were divided into three groups, with 30 patients in each group: EP, AI and healthy intrauterine pregnancy groups. Blood samples were taken from the antecubital vein and kept for HSP70 analysis. Results: The HSP70 levels were higher in the EP group than in AI patients and healthy controls (p<0.05). The area under the curve for the serum HSP70 assay reached a value of 0.81 for a cutoff point of 11.12pg/ml, whichidentified women with EP. Conclusion: Serum HSP70 levels increased in women with EP compared with healthy controls and women with AI.

Identification of noninvasive diagnostic biomarkers for ectopic pregnancy using data-independent acquisition (DIA)proteomics: a pilot study

At present, the diagnosis of ectopic pregnancy mainly depends on transvaginal ultrasound and β-hCG. However, these methods may delay diagnosis and treatment time. Therefore, we aimed to screen for serological molecular markers for the early diagnosis of ectopic pregnancy (EP).Using data-independent acquisition (DIA)proteomics, the differential proteins in serum were selected between the intrauterine pregnancy (IP) and EP groups. Then, the expression levels of these differential proteins were measured by enzyme-linked immunosorbent assay. The diagnostic value of the serum biomarkers was evaluated by receiver operating characteristic curve analysis.GSTO1, ECM-1 and β-hCG showed significant differences between the EP and IP groups (P < 0.05). The combination of GSTO1/ECM-1/β-hCG had an area under the curve of 0.93 (95% CI 0.88–0.99), a sensitivity of 88.89% (95% CI 73.94–96.89) and a specificity of 86.11% (95% CI 70.50–95.33) with a likelihood ratio of 6.40.The combination of GSTO1/ECM-1/β-hCG may be developed into a possible approach for the early diagnosis of EP.

O-258 Nuclear magnetic resonance profiling of the vaginal metabolome in adverse early pregnancy outcomes

Abstract Study question Is the vaginal metabolome predictive of early pregnancy outcomes? Summary answer The vaginal metabolome is moderately predictive of live normally-sited pregnancies when compared to a pregnancy with an adverse outcome. What is known already Approximately 15% of all pregnancies are lost in the first trimester and a further 1-2% are ectopic. To date, no non-invasive and clinically useful tests have been developed to differentiate live normally-sited pregnancies from non-viable and ectopic pregnancies. Metabolomics is the comprehensive analysis of small molecules in biological samples used to identify disease biomarkers. The vaginal metabolome has previously been shown to be predictive of later adverse pregnancy outcomes including preterm birth. In this study, we aimed to identify biomarkers of live normally-sited pregnancies when compared to non-viable intrauterine and ectopic pregnancies using NMR metabolomic profiling of vaginal swabs (LVS). Study design, size, duration This was a prospective cohort study (EXPEDITE). 222 pregnant women &amp;lt;10 weeks’ gestation with pain and/or bleeding were recruited over a period of 36 months at the Liverpool Women’s Hospital, a tertiary referral centre. Pregnancy outcomes were categorised according to ESHRE guidelines as live normally-sited pregnancy, miscarriage, tubal ectopic pregnancy or pregnancy of unknown location (PUL). Participants/materials, setting, methods Participants consented to self-collecting a LVS, which was extracted in acetonitrile and analysis by NMR spectroscopy; 1D 1H and 2D 1H-13C. Spectra were acquired at 25 °C on a 700 MHz spectrometer. Relative metabolite abundances underwent univariate and multivariate statistical analysis using MetaboAnalyst 5.0 and custom-built R scripts (p-value false discovery rate adjusted). Area under receiver operating characteristic curve (AUC) values were used to evaluate predictive models. Main results and the role of chance Our cohort of 222 women were categorised in to 100 (45 %) live normally-sited pregnancies, 29 (13 %) tubal ectopic pregnancies, 52 (23 %) miscarriages and 31 (14%) pregnancies of unknown location (PUL). Ten spectra from rare or uncertain pregnancy outcomes (e.g. molar pregnancy) were excluded. Univariate statistical analysis of all four groups identified isoleucine levels as significantly higher (p &amp;lt; 0.05) in live normally-sited pregnancies compared with all groups with adverse pregnancy outcome groups. Multivariate partial least squares discriminant analysis (PLS-DA) models of all groups failed to accurately predict pregnancy outcomes. To enhance the predictive models, miscarriage, tubal ectopic pregnancy and PUL groups were combined and compared to live normally-sited pregnancies. Univariate analysis revealed levels of several metabolites (including isoleucine, tyrosine and maltose) as significantly altered in live normally-sited pregnancies compared with all other outcomes. PLS-DA models demonstrated modest discrimination between live normally-sited pregnancies versus other outcomes (AUC = 0.75). In summary, this study has identified a vaginal metabolite profile and potential biomarkers associated with live normally-sited pregnancy in the first trimester. Limitations, reasons for caution The number of tubal ectopic pregnancies and PULs were relatively low compared to other outcomes. Additionally, several factors that may influence the vaginal metabolome, including infection and the vaginal microbiome, were not characterised in this study. Wider implications of the findings These findings may be useful in the development of diagnostic tests to confirm an intrauterine pregnancy and exclude potential life-threatening pregnancies. It is well established that the microbiome contributes to the vaginal metabolome. As such, our findings will inform future correlative studies of vaginal microbiome and metabolome in early pregnancy. Trial registration number NA

Risk factors and clinical characteristics associated with a ruptured ectopic pregnancy: A 19-year retrospective observational study.

Ectopic pregnancy is the most common cause of maternal mortality in the first trimester of pregnancy. The aim of this study was to find risk factors and clinical characteristics associated with ruptured ectopic pregnancies at a medical center in eastern Taiwan in a 19-year period. This was a retrospective observational study that included patients diagnosed with ectopic pregnancy between August 1999 and December 2018. Data about the demographic variables, initial presentation, pre-treatment beta-human chorionic gonadotropin levels, treatment routes (laparoscopy or laparotomy), surgical methods (salpingostomy or salpingectomy), operation time, blood loss amount, the status of ectopic pregnancy (ruptured or unruptured), the requirement for transfusion, and duration of hospital stay were collected. The categorical and continuous variables were analyzed using the correlation coefficients. This study included 225 women who were diagnosed as having an ectopic pregnancy. There were 49 and 176 women with unruptured and ruptured ectopic pregnancies, respectively. The beta-human chorionic gonadotropin levels, history of previous ectopic pregnancy, pelvic inflammatory disease, tubal surgery, abdominal history, and vaginal bleeding were not significantly different between the 2 groups. The ratio of women with abdominal pain was significantly higher in the ruptured ectopic pregnancy group than in the unruptured group (89.1% vs. 63.8%, respectively, P < .001). Preoperative hemoglobin was lower in the ruptured group compared with the unruptured group (P < .001). Blood loss, postoperative hemoglobin, and blood transfusion were significantly higher in the ruptured group than in the unruptured group (P = .000 and P = .001 for blood loss and blood transfusion, respectively). Multiple logistic regression analysis revealed that abdominal pain and blood loss were associated with ruptured tubal pregnancies (adjusted odds ratio [95% confidence intervals]: 3.42 {1.40, 8.40}; 1.01 {1.005, 1.014}, respectively). In conclusion, early pregnancy with abdominal pain, more parity, and lower preoperative hemoglobin should be aware of the possibility of ruptured ectopic pregnancy. More blood loss, transfusion and lower postoperative hemoglobin were also noted with ruptured ectopic pregnancy.

Time to pregnancy in women with previous ectopic pregnancy undergoing in vitro fertilization treatment: a retrospective cohort study

We aimed to investigate the difference in the time to pregnancy (TTP) between women with previous ectopic pregnancy (EP) and control women following in vitro fertilization (IVF) treatment and the association between TTP and the number of oocytes retrieved and embryos available. A retrospective study involving 1097 women, 547 of which had previous EP and 550 were control women whose previous pregnancy were abortion, was conducted. Women in the EP group had significantly longer median TTP than those in the control group (36; range, 12–252 vs 28; range, 12–220; P = 0.019). For women with previous EP, > 48 months TTP was most likely associated with low numbers of oocytes retrieved and embryos available compared to TTP of ≤ 24 months or 25–48 months, and women with younger age had a shorter TTP, higher numbers of oocytes retrieved and embryos available. A Cox proportional hazards model showed that maternal age was significantly related to the pregnancy over the TTP (adjusted hazard ratio, 0.934; P < 0.001). In conclusion, women with previous EP have a significantly increased TTP than control women with previous abortion. For women with previous EP, TTP is negatively associated with the numbers of oocytes retrieved and embryos available.

Antichlamydial Antibodies In Women With Ectopic Pregnancy

Methods: A case control study that was conducted in the Department of Obstetrics and Gynecology at Azadi Teaching Hospital / Kirkuk-Iraq during the period of 10 months from 1st of Feb till 1st of Dec 2019. It included 86 pregnant women selected from outpatient clinic and those who were admitted to the emergency department. They were divided into two groups: Case group included 43 women diagnosed with ectopic pregnancy and control group included 43 women with early normal intra uterine pregnancies (1st trimester). Women using an intrauterine contraceptive device at the time of conception or had previous history of ectopic pregnancy, infertility, tubal surgery or smoking were excluded . After obtaining verbal consent from them five ml of venous blood was collected from all women to investigate for serum anti chlamydial IgG antibody titer.Conclusion: Higher proportion of women with ectopic pregnancy had positive anti- chlamydial antibody than those with normal pregnancy. Anti-chlamydial antibody titer may play an important role to predict the risk of ectopic pregnancy as the mean of anti-chlamydial antibody titer was significantly higher in patients who diagnosed with ectopic pregnancy than that in women with normal pregnancy regardless age, gestational age or parity.

The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction

BackgroundNormal motor activity of the fallopian tube is critical for human reproduction, and abnormal tubal activity may lead to ectopic pregnancy (EP) or infertility. Progesterone has an inhibitory effect on tubal contraction; however, the underlying mechanisms remain unclear. Small-conductance calcium-activated K+ channel 3 (SK3) is abundantly expressed in platelet-derived growth factor receptor α positive (PDGFRα+) cells and was reported to be important for the relaxation of smooth muscle. The present study aims to explore the expression of SK3 in the human fallopian tube and its role in progesterone-induced inhibition of tubal contraction.MethodsWe collected specimens of fallopian tubes from patients treated by salpingectomy for EP (EP group) and other benign gynecological diseases (Non-EP group). The expression of SK3 was detected by quantitative real-time polymerase chain reaction, western blot, immunocytochemistry, and immunohistochemistry analyses. Isometric tension experiments were performed to investigate the role of SK3 in progesterone-induced inhibition of tubal contraction.ResultsThe baseline amplitude and frequency of human fallopian tube contraction were both statistically lower in the EP group compared with the non-EP group. The expression levels of SK3 in different portions of fallopian tubes from the non-EP group were significantly higher than in those from the EP group. Progesterone had an inhibitory effect on tubal contraction, mainly on the amplitude, in both groups, and SK3 as well as other calcium-activated K+ channels may be involved. SK3-expressing PDGFRα (+) cells were detected in the human fallopian tube.ConclusionsThe expression of SK3 is lower in the EP group, and SK3 is involved in the progesterone-induced inhibition of human fallopian tube contraction.

Differential expression of matrix metalloproteinases in the fallopian tube of women with Chlamydia trachomatis-associated tubal ectopic pregnancy

Chlamydia trachomatis is an established risk factor for ectopic pregnancy (EP) in fallopian tube (FT). Matrix metalloproteinases (MMPs) have potential role in disease pathogenesis, however, dysregulation of extracellular matrix by MMPs/TIMPs (tissue inhibitors of MMPs) in infection-associated EP remains unknown. The aim was to study the expression of MMP-2, -9, -14/TIMP-1, -2, -3 in C. trachomatis-positive tubal EP patients. The study comprised of 100 tubal EP (Group I) and 100 tubal ligation patients (Group II; controls) enrolled from Department of Obstetrics and Gynaecology, VMMC and Safdarjung hospital, New Delhi (India) for collection of FT. Detection of C. trachomatis MOMP was done by PCR while quantitative expression of MMPs/TIMPs was studied by real-time PCR. Data was statistically evaluated by Graphpad prism. Overall, C. trachomatis was found in 18/100 tubal EP patients. After ruling out Neisseria gonnorhoeae and Mycoplasma genitalium, Group I was divided into Group Ia (C. trachomatis DNA-positive) and Group Ib (C. trachomatis DNA-negative; internal controls). Significant upregulation of MMP-2, -9, -14 and downregulated TIMP-1, -2, -3 were found in Group Ia versus controls (Groups Ib/II) (p < 0.05). Fold-change in MMP was significantly higher in Group Ia versus controls (‘p’ < 0.05). Maximum 5.5-fold upregulation was found in MMP-2. It is apparent by molecular analysis that differential expression of MMPs/TIMPs, particularly enhanced MMP-2 leads to tubal EP in C. trachomatis DNA-positive women.

Role of telocytes in the pathogenesis of ectopic pregnancy.

The aim of this study is to investigate the effect of telocytes on tubal motility in ectopic pregnancies. This study included patients with ectopic pregnancy (EP) (n=10) and control patients (n=10) (partial salpingectomy for contraception). Immunohistochemical staining for c-Kit, vimentin, CD34 and S100A was performed to quantify telocytes in the mucosa, muscular layer and serosa of fallopian tubes of control and EP group. Spontaneous and KCl- (80 mM) induced contraction and cumulative progesterone dose-relaxation (10-11-10-5 M) and cumulative oxytocin dose-contraction (10-10-10-4 M) responses were recorded. The groups were comparable in terms of age, gravida, parity, delivery type and gestational week (p>0.05). The homogenous distribution of telocytes in the mucosa and muscular layers of the control group, changed to heterogeneous localization the EP group. Immunohistochemical staining with vimentin, S100A, c-Kit and CD34, revealed increased telocyte counts in the muscular layer and serosa of the tubal tissues of EP. The frequency of the spontaneous contractions was higher in the control group (p<0.001); contrarily, the amplitude of the contractions was higher in ectopic pregnancies (p<0.001). Although the cumulative oxytocin dose-contraction curves were similar at all concentrations (p>0.05), the cumulative progesterone dose-relaxation curves exhibited higher relaxation response in the EP group at all concentrations (p<0.001). Increased telocyte count in the fallopian tube may decrease tubal motility and may affect the transfer of the blastocyst to the uterus and possibly contribute to the pathogenesis of EP.

Evaluation of Oxidative Stress in Ectopic Pregnancies.

Purpose:The aim of the study is to show the relationship between oxidative stress and ectopic pregnancy.Materials and Methods:A total of 62 patients, 31 in the ectopic pregnancy group (study group) and 31 in the first-trimester pregnancy (control group) were included in the study. Patients between 18-45 years of age who had tubal ectopic pregnancy diagnosed by transvaginal ultrasonography and serum β-HCG values were included in the study group. Serum thiol- disulfide hemostasis were measured from venous blood.Results:Between the control group and the ectopic pregnant group; there was no statistically significant difference in terms of age, total thiol, albumin, disulfide, index 1 (disulfide / total thiol), index 2 (disulfide / native thiol), and index 3 levels (p> 0.05). The area under the ROC curve for native thiol measurements was statistically significant in distinguishing the control group and the ectopic pregnant group [AUC = 0.657, 95% CI: 0.521-0.793, p = 0.034].Conclusion:This study shows that ectopic pregnancies may be associated with the presence of high oxidative stress. Especially in early stage suspected patients, demonstrating the presence of oxidative stress together with serial β-HCG follow-up may be helpful in diagnosis. (www.actabiomedica.it)

Triaging Women with Pregnancy of Unknown Location: Evaluation of Protocols Based on Single Serum Progesterone, Serum hCG Ratios, and Model M4.

Background:The purpose of the current study was to evaluate the ability of three protocols to triage women presenting with pregnancy of unknown location (PUL).Methods:Women with pregnancy of unknown location were recruited from Aziz Medical Centre from 1st August, 2018 to 31st July, 2020. The criterion of progesterone, human chorionic gonadotrophin (hCG) ratio, and M4 algorithm were used to predict risk of adverse pregnancy outcomes and classify women. Finally, 3 groups were established including ectopic pregnancy, failed pregnancy of unknown location, and intrauterine pregnancy (IUP). The primary outcome was to assign women to ectopic pregnancy group using these protocols. The secondary outcome was to compare the sensitivity and specificity of the three protocols relative to the final outcome.Results:Of the 288 women, 66 (22.9%) had ectopic pregnancy, 144 (50.0%) had intrauterine pregnancy, and 78 (27.1%) had failed pregnancy of unknown location. The criterion of progesterone had a sensitivity of 81.8%, specificity of 27%, negative predictive value (NPV) of 83.3%, and positive predictive value (PPV) of 25% for high risk result (ectopic pregnancy). The hCG ratio had sensitivity of 72%, specificity of 73%, NPV of 90%, and PPV of 44% for high risk result (ectopic pregnancy). However, model M4 had sensitivity of 86.4%, specificity of 91.9%, NPV of 95.8%, and PPV of 76% for high risk result.Conclusion:Based on the findings of the study, it was revealed that prediction model of M4 had the highest sensitivity, specificity, negative predictive value and positive predictive value for high risk result (ectopic pregnancy).