Early (Days 1-4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy.

STUDY QUESTION: What is the capacity of the change between Day 1 and Day 4 post-treatment serum human chorionic gonadotropin (hCG) levels for predicting single-dose methotrexate treatment success in tubal ectopic pregnancy? SUMMARY ANSWER: Any fall in Days 1-4 serum hCG signified an 85% (95% CI 76.8-90.6) likelihood of treatment success for women with tubal ectopic pregnancy (initial hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate. WHAT IS KNOWN ALREADY: For those with tubal ectopic pregnancy managed by single-dose methotrexate, current guidelines advocate intervention if Days 4-7 hCG fails to fall by >15%. The trajectory of hCG over Days 1-4 has been proposed as an early indicator that predicts treatment success, allowing early reassurance for women. However, almost all prior studies of Days 1-4 hCG changes have been retrospective. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study of women with tubal ectopic pregnancy (pre-treatment hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate. The data were derived from a UK multicentre randomized controlled trial of methotrexate and gefitinib versus methotrexate and placebo for treatment of tubal ectopic pregnancy (GEM3). For this analysis, we include data from both treatment arms. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were categorized according to single-dose methotrexate treatment success or failure. Treatment success for this analysis was defined as complete and uneventful resolution of tubal ectopic pregnancy to serum hCG <30 IU/l following single-dose methotrexate treatment without additional treatment. Patient characteristics of the treatment success and failure groups were compared. Changes in Days 1-4, 1-7, and 4-7 serum hCG were evaluated as predictors of treatment success through receiver operating characteristic curve analysis. Test performance characteristics were calculated for percentage change ranges and thresholds including optimal classification thresholds. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 322 women with tubal ectopic pregnancy were treated with single-dose methotrexate. The overall single-dose methotrexate treatment success rate was 59% (n = 189/322). For any fall in serum hCG on Days 1-4, likelihood ratios were >3, while for any fall of serum hCG >20% on Days 1-7, likelihood ratios reached 5. Any rise of serum hCG on Days 1-7 and 4-7 strongly reduced the chance of success. Any fall in Days 1-4 hCG predicted single-dose methotrexate treatment success with a sensitivity of 58% and specificity 84%, resulting in positive and negative predictive values of 85% and 57%, respectively. Any rise in Days 1-4 serum hCG <18% was identified as an optimal test threshold that predicted treatment success with 79% sensitivity and 74% specificity, resulting in 82% positive predictive value and 69% negative predictive value. LIMITATIONS, REASONS FOR CAUTION: Our findings may be limited by intervention bias resulting from existing guidelines which influences evaluation of hCG changes reliant on Day 7 serum hCG levels. WIDER IMPLICATIONS OF THE FINDINGS: Examining a large prospective cohort, we show the value of Days 1-4 serum hCG changes in predicting single-dose methotrexate treatment success in tubal ectopic pregnancy. We recommend that clinicians provide early reassurance to women who have a fall or only a modest (<18%) rise in Days 1-4 serum hCG levels, that their treatment will likely be effective. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by funding from the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership (grant reference number 14/150/03). A.W.H. has received honoraria for consultancy for Ferring, Roche, Nordic Pharma and AbbVie. W.C.D. has received honoraria from Merck and Guerbet and research funding from Galvani Biosciences. L.H.R.W. has received research funding from Roche Diagnostics. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. also reports consultancy for ObsEva and Merck and travel support from Merck. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER: This study is a secondary analysis of the GEM3 trial (ISRCTN Registry ISRCTN67795930).

Cornuostomy and Cornuectomy: Laparoscopic Management of Interstitial Ectopic Pregnancies.

OBJECTIVE: To demonstrate and contrast 2 techniques of laparoscopic management of interstitial ectopic pregnancies. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary referral center in Manchester, United Kingdom. INTERVENTIONS: Nontubal ectopic pregnancies typically involve the cervix, ovary, myometrium, cesarean scar, and the interstitial portion of the fallopian tube. Interstitial ectopic pregnancies account for 2% of all ectopic pregnancies [1] and are caused by implantation of a fertilized embryo within the proximal and intramural portion of the fallopian tube [2]. They represent specific challenges in diagnosis and management and are associated with increased morbidity and mortality when compared with tubal ectopic pregnancies [3]. The techniques for minimal access surgical management includes laparoscopic cornuectomy and cornuostomy. We present 2 cases of interstitial ectopic pregnancies managed laparoscopically using the 2 different techniques. Case 1: A 33-year-old women, para 2+1, presented at 8 weeks' gestation with lower abdominal pain, vaginal bleeding, and an episode of loss of consciousness. An ultrasound scan showed a gestational sac lateral and posterior to the endometrial cavity with the interstitial line sign present. A yolk sac and a 2-mm fetal pole were noted with fetal heart action present. At laparoscopy, an 800 mL hemoperitoneum was noted, and a laparoscopic cornuectomy was performed (Fig. S1). Operating time was 80 minutes, and she was discharged on day 1 postoperation. Case 2: A 34-year-old women, para 1, presented at 6 weeks' gestation to her local hospital with symptoms of vaginal bleeding and intermittent abdominal pain. A diagnosis of an interstitial ectopic pregnancy was suspected on the ultrasound scan, and conservative management was started because the diagnosis was uncertain. A follow-up scan 7 days later confirmed the diagnosis of a live interstitial ectopic pregnancy, and after consultation, she presented herself to a tertiary referral unit. Serum human chorionic gonadotropin was greater than 11 000 IU/L and 2-dimensional ultrasound scan confirmed the presence of a gestational sac with a yolk sac and fetal pole within the left interstitial space. A slow fetal heart action was seen. A diagnosis of a left interstitial ectopic pregnancy was further confirmed on 3-dimensional ultrasound scan. A laparoscopic cornuostomy was performed as demonstrated in the attached video (Figs. S2-S3). Operating time was 38 minutes with minimal blood loss. At day 7, serum human chorionic gonadotropin level was 364 IU/L. CONCLUSION: Although more research is needed to determine the optimal surgical technique for the management of interstitial ectopic pregnancies, the potential risks and benefits of different techniques should be discussed with the patient, and an individual decision should be made. This decision often depends on the desire for future fertility and previous gynecologic history.

Can early ßhCG change and baseline progesterone level predict treatment outcome in patients receiving single dose Methotrexate protocol for tubal ectopic pregnancy?

INTRODUCTION: We aimed to assess the prognostic significance of early ßhCG change and baseline progesterone level on treatment outcome among women receiving single dose Methotrexate protocol for tubal ectopic pregnancy (EP). MATERIAL AND METHODS: Retrospective study involving all consecutive patients diagnosed with EP and receiving Methotrexate therapy form January 2015 to December 2016. Patients were stratified into 2 groups according to treatment outcome: success group (n = 66) involved women who displayed complete resolution of serum ßhCG levels following a single course of Methotrexate; failure group (n = 55) included patients who required repeated Methotrexate administration and/or surgical management. Predictive performances of baseline progesterone and ratio"ßhCG level on day 4/ ßhCG level on day 1″ (d4/d1) on treatment outcome were assessed using Receiving Operating Characteristics curves. RESULTS: The ratio d4/d1 displayed good performances in predicting treatment outcome (AUC = 0.826). A ratio ≤ 0.7 was associated with a success rate of 94% after 1 course of Methotrexate and 100% after 2 courses. In contrast, a ratio >1.7 was associated with a failure rate of 100%. Conversely, baseline progesterone showed poor performances (AUC = 0.611). CONCLUSIONS: Patients with extreme ßhCG changes (n = 33) on day 4 might benefit from a more personalized approach: simplified monitoring in those with a decline ≥30%, anticipated second course of treatment in those with an increase > 70%.

[Hysteroscopically assisted laparoscopic salpingostomy in the treatment of tubal pregnancy]. / Hysteroskopicky asistovaná laparoskopická salpingostomie pri resení tubární gravidity.

OBJECTIVE: To present a case of conservative - Fallopian tube preserving - surgical therapy of tubal pregnancy. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Strakonice Hospital. CASE DESCRIPTION: Due to the desire to preserve the Fallopian tube in a hemodynamically stable primigravida, we decided for laparoscopic salpingostomy using hysteroscopy for assisted removal of pregnancy tissue from the oviduct. CONCLUSION: In well-selected cases, this treatment is an effective method of choice and can be performed even under conditions of a smaller hospital performing a common spectrum of laparoscopic surgery.

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

OBJECTIVE: Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy. METHODS: This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (ß-hCG) level of < 1500 IU/L. Women were assigned randomly to a single systemic injection of either 50 mg/m2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum ß-hCG to < 20 IU/L or a negative urine pregnancy test without the need for any additional medical intervention. An intention-to-treat analysis was followed. RESULTS: We recruited a total of 80 women, 42 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of ß-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of ß-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in ß-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum ß-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the subgroup of women with higher ß-hCG. In women with successful conservative treatment, there was no significant difference in median ß-hCG resolution times between study arms (17.5 (interquartile range (IQR), 14-28.0) days (n = 30) in the methotrexate group vs 14 (IQR, 7-29.5) days (n = 25) in the placebo group; P = 0.73). CONCLUSIONS: The results of our study do not support the routine use of methotrexate for the treatment of clinically stable women diagnosed with tubal ectopic pregnancy presenting with low serum ß-hCG (< 1500 IU/L). Further work is required to identify a subgroup of women with tubal ectopic pregnancy and ß-hCG ≥ 1500 IU/L in whom methotrexate may offer a safe and cost-effective alternative to surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Comparación entre una sola dosis de metotrexate sistémico y la conducta expectante en el tratamiento de casos de embarazo ectópico tubárico: un ensayo aleatorio controlado con placebo RESUMEN OBJETIVO: El metotrexate se utiliza de modo rutinario en todo el mundo para el tratamiento de las mujeres clínicamente estables con un embarazo ectópico tubárico. Esto sucede a pesar de la falta de evidencia rigurosa que demuestre que su eficacia es superior a la conducta expectante. El objetivo de este ensayo controlado aleatorio multicéntrico fue comparar las tasas de éxito del metotrexate con las de un placebo para el tratamiento cauteloso del embarazo ectópico tubárico. MÉTODOS: Este estudio se llevó a cabo en dos clínicas de control de gestación temprana en el Reino Unido entre agosto de 2005 y junio de 2014. Los criterios de inclusión fueron mujeres clínicamente estables con un diagnóstico ecográfico concluyente de embarazo ectópico tubárico, las cuáles presentaban una concentración sérica baja de la ß hormona coriónica gonadotrópica (ß-hCG) inferior a 1500 UI/L. Las mujeres fueron asignadas aleatoriamente a una sola inyección sistémica de 50 mg/m2 de metotrexate o a placebo. El resultado primario fue un indicador binario del éxito del tratamiento conservador, definido como la resolución de los síntomas clínicos y la disminución en el suero de la ß-hCG a <20 UI/L o una prueba de embarazo negativa en orina sin la necesidad de ninguna intervención médica adicional. Se hizo un análisis por intención de tratar. RESULTADOS: Se reclutó un total de 80 mujeres; a 42 de ellas se les asignó el metotrexate y a 38 el placebo. Los grupos del estudio se realizaron en función de la edad, el origen étnico, los antecedentes obstétricos, las características del embarazo y los niveles séricos de la ß-hCG y la progesterona. Las tasas de éxito fueron similares para los dos grupos de estudio: 83% con metotrexate y 76% con placebo. En el análisis univariante, esta diferencia no fue estadísticamente significativa (χ2 (1 grado de libertad) = 0,53; P = 0,47). En la regresión logística multivariante, el nivel sérico de la ß-hCG fue la única covariable que se encontró significativamente asociada con el resultado. Las probabilidades de fracaso aumentaron en un 0,15% por cada unidad de aumento de la ß-hCG (cociente de probabilidad 1,0015 (IC 95%, 1,0002-1,003); P = 0,02). La tasa de éxito en las 14 mujeres con un nivel sérico de la ß-hCG de 1000-1500 UI/L fue del 33% en las tratadas con conducta expectante frente al 62% en las que recibieron metotrexate. Esta diferencia no fue estadísticamente significativa, por lo que se necesitaría un tamaño de muestra mayor, lo suficiente como para poder detectar diferencias en el subgrupo de mujeres con una ß-hCG más elevada. En las mujeres en las que el tratamiento conservador tuvo éxito, no hubo una diferencia significativa en la mediana de los tiempos de resolución de la ß-hCG entre los grupos del estudio (17,5 (amplitud intercuartílica (IQR), 14-28,0) días (n = 30) en el grupo de metotrexate frente a 14 (IQR, 7-29.5) días (n = 25) en el grupo de placebo; P = 0,73). CONCLUSIONES: Los resultados de este estudio no apoyan el uso rutinario de metotrexate para el tratamiento de las mujeres clínicamente estables diagnosticadas con un embarazo ectópico tubárico que presenta un nivel sérico bajo la ß-hCG (<1500 UI/L). Serán necesarios estudios adicionales para identificar un subgrupo de mujeres con embarazo ectópico tubárico y ß-hCG ≥1500 UI/L para quienes el metotrexate puede ofrecer una alternativa segura y rentable en comparación con la cirugía. : : ,,。。 : 2005820146,2。,,ß(beta human chorionic gonadotropin,ß-hCG)<1500 IU/L。,(50 mg/m2 )。,ß-hCG<20 IU/L,。。 : 80,42,38。2、、、ß-hCG。2:83%,76%。,[χ2 (1)=0.53;P=0.47]。logistic,ß-hCG。ß-hCG,0.15%[,1.0015(95% CI,1.0002~1.003);P=0.02]。14ß-hCG1000~1500 IU/L,33%,62%。,ß-hCG。,2ß-hCG(P=0.73),17.5[(interquartile range,IQR),14~28.0](n=30),14 (IQR,7~29.5)(n=25)。 : 、、ß-hCG(<1500 IU/L)。,ß-hCG>1500 IU/L、。.

Management of non-tubal ectopic pregnancies at a large tertiary hospital.

There are limited data on the management of non-tubal ectopic pregnancies (NTEP). We reviewed the management of these cases at a tertiary centre with a dedicated institutional protocol. All cases of confirmed NTEP were retrospectively identified from 2006 to 2014. Records were reviewed for presenting features, mode and success of initial management, preservation of fertility and length of hospital stay. The main outcome measure was the success rate of medical management with methotrexate. The 60 cases identified included 34 cornual, 14 Caesarean section scar, nine cervical and three cervical involving previous Caesarean scar. Primary surgical management was performed in 22 patients. Thirty-eight patients received medical therapy with single or multidose methotrexate. Successful medical management was observed in 33 (87%); however, length of stay was significantly longer compared with surgical patients (mean 14 ± 12 days versus 5 ± 2 days, P < 0.01). Hysterectomy was performed in three patients (one surgical group, two medical group). There was one case of methotrexate toxicity with no long-term adverse outcome. Medical management of NTEP is a safe first-line therapy for clinically stable patients desiring preservation of fertility despite a longer period of inpatient monitoring and follow-up.

Telocytes in Inflammatory Gynaecologic Diseases and Infertility.

Women suffered with inflammatory gynecologic diseases, such as endometriosis (EMs) and acute salpingitis (AS) often complained of sub- or infertility, even in those women without obvious macroscopic anatomical pelvic abnormalities also have unexplained infertility. Generally, besides the well-known impairment of classically described oviduct cells caused by inflammatory diseases, such as the ciliated cells, fibroblasts and myofibroblasts, the involvement of the newly identified telocytes (TCs) in disease-affected oviduct tissues and potential pathophysiological roles in fertility problems remain unknown. In this chapter, TCs was investigated in rat model of EMs- and AS-affected oviduct tissues. Results showed inflammation and ischaemia-induced extensive ultrastructural damages of TCs both in cellular body and prolongations, with obvious TCs loss and interstitial fibrotic remodelling. Such in vivo pathological alterations might contribute to structural and functional abnormalities of oviduct tissue and potentially engaged in sub- or infertility. And especially, TCs connected to various activated immunocytes in both normal and diseased tissues, thus might participate in local immunoregulation (either repression or activation) and serve a possible explanation for immune-mediated pregnancy failure. Then, in vitro cell co-culture study showed that uterine TC conditioned media (TCM) can activate mouse peritoneal macrophages and subsequently trigger its cytokine secretion, thus providepreliminary evidence that, TCs are not simply innocent bystanders, but are instead potential functional players in local immunoregulatory and immunosurveillance.

Telocytes damage in endometriosis-affected rat oviduct and potential impact on fertility.

Women with endometriosis (EMs) have unexplained infertility. The recently identified telocytes (TCs) might participate in the maintenance of structural and functional integrity of oviduct tissue, but so far the involvement of TCs in EMs-affected oviduct tissue and potential impact on fertility capacity remain unknown. By an integrated technique of haematoxylin and eosin staining, in situ immunohistochemistry and double-labelled immunofluorescence staining and electron microscopy approach, TCs were studied in the autotransplantation Sprague-Dawley rat model of EMs-affected oviduct tissue and in sham control, respectively, together with determination of iNOS, COX-2, LPO and estradiol. TCs were found in perivascular connective tissue and smooth muscle bundles in sham oviduct, with typical ultrastructural features (a slender piriform/spindle/triangular cell body, and one or more extremely long prolongations, emerged from cell bodies and extend to various directions), and specific immunophenotype of CD34-positive/vimentin-positive/c-kit-negative. However, in EMs-affected oviduct tissue (grade III), extensive ultrastructural damage (degeneration, discontinue, dissolution and destruction), significant decrease or loss of TCs and interstitial fibrosis were observed, together with elevated level of iNOS, COX-2, LPO and estradiol, thus suggestive of inflammation and ischaemia-induced TCs damage. Based on TCs distribution and intercellular connections, we proposed that such damage might be involved in structural and functional abnormalities of oviduct, such as attenuated intercellular signalling and oviduct contractility, impaired immunoregulation and stem cell-mediated tissue repair, 3-D interstitial architectural derangement and tissue fibrosis. Therefore, TCs damage might provide a new explanation and potential target for EMs-induced tubal damage and fertility disorders.

Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis.

Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local inflammatory process/ immunoregulation and possibly immune-mediated early pregnancy failure.

Nonsurgical management of live tubal ectopic pregnancy by ultrasound-guided local injection and systemic methotrexate.

STUDY OBJECTIVE: To evaluate outcomes relative to treatment using systemic methotrexate (MTX) alone or systemic MTX combined with ultrasound (US)-guided local injection of potassium chloride (KCl) or MTX in women with live tubal ectopic pregnancies. DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: Departments of Obstetrics and Gynecology in 2 hospitals in China. PATIENTS: Eighty-two women with live tubal ectopic pregnancies. INTERVENTION: Participants in the study received treatment using either systemic MTX (n = 37; systemic treatment group) or systemic MTX and US-guided local injection of either MTX or KCl (n = 45; combined treatment group). MEASUREMENTS AND MAIN RESULTS: Patient clinical features and outcomes were compared. There were no significant differences between the patient groups insofar as baseline gestational age, ß-human chorionic gonadotropin concentration, or size of conceptus. The success rate in patients who received combined therapy (93.3%) was much higher than in those who received only systemic treatment (73.0%) (p < .05). In the combined treatment group, the success rate was similar between women who received locally injected KCl (95.2%) and those who received locally injected MTX (91.7%). CONCLUSION: The significantly higher success rate in patients who received combined US-guided local injection and systemic MTX suggests that this is an efficient nonsurgical option in women with tubal pregnancy, high serum ß-human chorionic gonadotropin concentration, and fetal cardiac activity.

Unusual presentation of late-stage ectopic tubal pregnancy (19 weeks' gestation): Case report and literature review.

Ectopic pregnancy is a medical condition in which a fertilized egg takes an unexpected detour away from the uterine cavity and the fallopian tube becomes a popular host, with the ampulla being the prime location. However, it can occur in other areas such as cervix, ovaries, or abdomen. The most common risk factors are pelvic inflammatory disease, previous pelvic or abdominal surgery, abnormal anatomy of genital organs, endometriosis, previous ectopic pregnancies, assisted reproductive technologies, endocrine disorders, and even the subtle influence of low-dose progestins from contraceptives. We will present a rare case of unrecognized late-stage tubal ectopic pregnancy. The following case report is of a 25-year-old Caucasian female patient (G2, P0) who presented to the emergency department with a 24-hour abdominal pain syndrome. The patient did not have a gynecological examination for this reason. During the examination, taking into account the clinical and ultrasound findings, a suspicion of pregnancy in a bicornuate uterus was raised, and an MRI of the pelvis was performed. MRI showed ectopic pregnancy in the left fallopian tube with a properly developed fetus that corresponded to a gestation of 19 weeks. An emergency laparotomy was performed and the left fallopian tube with the fetus was removed. The early and late course of recovery went smoothly. The patient was discharged after adequate clinical development.

Screening of single nucleotide polymorphism in matrix metalloproteinase-2 (MMP2) and tetraspanin CD63 genes in Chlamydia trachomatis-infected tubal ectopic pregnancy patients.

OBJECTIVE: Tubal ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality. Studies have suggested that infection-induced inflammatory responses are major risk factors for EP. The aim of the present study was to find an association between MMP2 and CD63 gene variants and risk of EP during Chlamydia trachomatis infection in an Indian population. METHODS: Fallopian tube samples of 120 EP and 120 tubal ligation women were collected. C. trachomatis was detected by PCR. The genotyping of MMP2 (rs17859882 G/T, rs7201A/C) and CD63(rs2231464 C/T, rs376086542 A/G) gene variants was done by qualitative real-time PCR using allelic discrimination method (VIC- and FAM-labeled). RESULTS: The frequency of GG or GT genotype of MMP2 G/T polymorphism (rs17859882) was 66.6% in infected EP and 36.7% in uninfected EP and 22% in tubal ligation controls (P < 0.0001), while the frequency of AC or CC genotype of MMP2 A/C polymorphism (rs7201) was 66.6% in infected EP and 20.6% in uninfected EP and 13.5% in tubal ligation controls (P < 0.0001). The frequency of CT or TT genotype of CD63 C/T polymorphism (rs2231464) was 74% in infected EP and 21.8% in uninfected EP and 11.8% tubal ligation controls (P < 0.0001), while the frequency of AG or GG genotype of CD63 A/G polymorphism (rs376086542) was 48.1% in infected EP and 41.3% in uninfected EP and 18.6% tubal ligation controls (P < 0.0001). CONCLUSIONS: The present study revealed a strong association between the presence of gene variants MMP2 (rs17859882 G/T, rs7201A/C) and CD63 (rs2231464 C/T, rs376086542 A/G) and risk of tubal EP during C. trachomatis infection.

Bilateral tubal ectopic pregnancy following induction ovulation can be missed in emergent ultrasonography: Case report.

INTRODUCTION: Bilateral tubal ectopic pregnancy (BTP) is a rare and potentially life-threatening condition that is, often challenging to diagnose preoperatively. PRESENTATION OF CASE: We present a case of BTP in a 25-year-old primigravid woman with a history of infertility due to polycystic ovarian syndrome. She was receiving letrozole when she presented with severe abdominal pain and vaginal bleeding. Initial evaluation revealed a ruptured ectopic pregnancy in the right fallopian tube, prompting an emergency laparotomy. During surgery, a second intact ectopic mass was discovered in the left fallopian tube, highlighting the diagnostic complexity of BTP. Management involved a salpingectomy on the right side and salpingostomy on the left to preserve fertility. DISCUSSION: This case underscores the importance of considering BTP in the differential diagnosis of ectopic pregnancies and the necessity for thorough preoperative imaging studies, namely ultrasonography and surgical exploration, to prevent missed diagnoses. CONCLUSION: BTP is a rare and challenging clinical entity that requires a comprehensive approach to diagnosis and management. Early recognition, prompt intervention, and close surveillance are essential to mitigate the risk of maternal morbidity and mortality associated with this condition.

Cervical ectopic pregnancy: A case report of a massive pregnancy with a minimally invasive blood-free treatment and a review of the literature.

Cervical ectopic pregnancy is one of the rarest types of pregnancy, representing less than 1 % of ectopic pregnancies. We report the case of minimally invasive management of a voluminous cervical ectopic pregnancy at 9 weeks gestation using uterine artery embolization and in situ methotrexate. During follow-up, we encountered no hemorrhagic complications, while ß-hCG values returned to normal by Day 104 and the uterine cavity fully recovered within 6 months. Additionally, we present a review of the literature on this topic.

Superfetation and heterotopic pregnancy: Case report of two rare phenomena coexisting and implications in the era of assisted reproductive technologies.

Key Clinical Message: To raise awareness about the increasing incidence of superfetation and heterotopic pregnancy in patients with ovarian induction, their insidious symptoms of abdominal pain, anemia, and hemodynamic instability in early pregnancy, and the usefulness of transvaginal ultrasound (TVUS) and quantitative beta human chorionic gonadotrophin (b-hCG) for diagnosis. Abstract: Superfetation, occurrence of ovulation, fertilization, and implantation during an ongoing pregnancy and heterotopic pregnancy (HP) simultaneous presence of intrauterine and extrauterine pregnancies are infrequent phenomena. We report a case where both coexisted, challenges in diagnosis and management and association with the widespread use of assisted reproductive technologies (ARTs). A 32-year-old woman, who previously underwent ovulation induction therapy, presented with abdominal pain at 8 weeks pregnancy according to her last menstrual period. The patient had high quantitative serum beta-human chorionic gonadotropin (b-hCG) (30,883 mIU/mL). She was vitally stable and not anemic. Transvaginal ultrasound (TVUS) revealed two pregnancies at different gestational ages: an intrauterine pregnancy at 5 weeks and 3 days, and a right intact tubal ectopic pregnancy at 10 weeks and 5 days. Superfetation resulting in HP was then diagnosed. Subsequently, the patient underwent right laparoscopic salpingectomy. The intrauterine pregnancy progressed normally, resulting in delivery of a healthy full-term neonate via Cesarean section at 38 weeks. Superfetation is typically rare from suppression of follicular development and ovulation during pregnancy. Various theories have been proposed to explain its etiology, including polyovulation, delayed blastocyst implantation, and abnormal estrogen and b-hCG surges. In superfetation, an embryo resulting from a previous conception coexists with another embryo, either intrauterine, resulting in diamniotic dizygotic twins with significantly different gestational ages, or extrauterine resulting in HP. Despite being particularly challenging to diagnose because its presenting symptoms can overlap with those of other more common clinical conditions in early pregnancy, HP is increasingly seen with ARTs. In addition, the treatment of HP is versatile, ranging from expectant management to laparoscopic surgery. High level of suspicion for HP and superfetation is crucial in patients who, after ART, present with abdominal pain, hemodynamic instability, or anemia. Additionally, patients planning to undergo subsequent ART cycles should be thoroughly screened with b-hCG and TVUS to exclude an ongoing intrauterine or extrauterine pregnancy.

Diagnostic significance of total creatine kinase and its isoform in tubal ectopic pregnancy.

AIM: Tubal ectopic pregnancy (tEP) must be diagnosed as early as possible because it is one of the leading causes of pregnancy-related death in the first trimester. The aim of this study was to evaluate the diagnostic value of serum total creatine kinase (CK) and its isoforms in diagnosis of tEP. METHODS: The study included 32 tEP cases, and gestational age-matched intrauterine (IU) abortion and normal pregnancy cases (n = 31 each). Serum total CK and CK-MB fraction were measured by the principle of spectrophotometry and CK-MM fraction was calculated from the above parameters. Serum ß-hCG was measured using chemiluminescent immunoassay. All study parameters were measured at the time of presentation. RESULTS: Serum ß-hCG levels were significantly low in patients with both tEP and IU abortion than normal pregnancy. Women with tEP had higher concentrations of total CK, CK-MM and lower concentrations of CK-MB% compared to both gestational age-matched IU pregnancy controls and IU abortion. Receiver-operator characteristic analysis revealed that the optimal cut-off for total CK, CK-MM and CPK-MB% as predictors of ruptured EP were 147 IU/L, 135 IU/L and 10%, respectively, with the former two having higher specificity, and latter high sensitivity. CONCLUSION: Estimation of CK and its CK isoenzyme fractions can aid in quick and accurate diagnosis of tEP.

Subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate.

Lay summary: An ectopic pregnancy occurs when an embryo implants outside of the uterus, usually in a fallopian tube. When detected early, treatment is often with a medication called methotrexate. When methotrexate does not work, surgery is required. A recent clinical trial of ectopic pregnancy treatment (called GEM3) found that adding a drug called gefitinib to methotrexate did not reduce the need for surgery. We have used data from the GEM3 trial, combined with data collected 12 months after the trial finished, to investigate post-methotrexate pregnancy outcomes. We found no difference in pregnancy rates, pregnancy loss rates and recurrent ectopic pregnancy rates between those treated medically only and those who subsequently also needed surgery. The surgical technique used also did not affect pregnancy rates. This research provides reassurance that women with ectopic pregnancies treated medically who need surgery have similar post-treatment pregnancy outcomes to those treated successfully medically.

Mechanism of Human Tubal Ectopic Pregnancy Caused by Cigarette Smoking.

In the past few decades, the smoking rate of women of childbearing age has increased. Epidemiological data has repeatedly shown that smoking women have an increased risk of various reproductive diseases, including ectopic pregnancy (EP), decreased fertility, adverse pregnancy outcomes, and failure of assisted reproduction. The oviduct was the target of cigarette smoke in many in vivo and in vitro studies. The fallopian tube is a well-designed organ. Its function is to collect and transport the ova to the fertilized site and provide a suitable environment for fertilization and early embryonic development. Lastly, the fallopian tube transports the pre-implantation embryo to the uterus. Various biological processes can be studied in the fallopian tubes, making it an excellent model for toxicology. This paper reviews the roles of the fallopian tube in gametes and embryo transportation, and the possible mechanism tobacco smoke contributes to tubal EP. A possible signal pathway might be a model to develop intervention of EP for pregnant women exposed to smoking.

Case report of a lithopedion of tubal location, in a young woman.

Lithopedion is a rare situation, corresponding to an ectopic pregnancy which evolves beyond the first trimester toward death and fetal calcification. This ectopic pregnancy is most often abdominal in location. Through this case report, we report the case of a lithopedion of left tubal localization in a young woman, diagnosed on CT scan following abdominal pain and confirmed by laparotomy with excision.

A Spontaneous Heterotopic Pregnancy Presenting as Acute Appendicitis.

Heterotopic pregnancy (HP) occurs when there is a simultaneous intrauterine and extrauterine pregnancy, either viable or non-viable. Although spontaneous HP is rare, it is important to consider this possibility. Acute appendicitis (AA) is a common non-obstetric surgical emergency in pregnant women. Diagnosing HP can be challenging, particularly in pregnant women who present with symptoms such as right iliac fossa pain and an acute abdomen. As HP may not be initially suspected in the presence of a viable intrauterine pregnancy, we present an intriguing case of spontaneous HP initially presenting as AA, along with a literature review. Our objective is to raise awareness of HP among trainee obstetricians and general surgeons.