Desenlaces maternos y perinatales en pacientes con infección respiratoria aguda COVID-19 de Cartagena (marzo a diciembre de 2020), Colombia / Maternal and perinatal outcomes in patients with acute respiratory infection COVID-19 from Cartagena (March to December 2020), Colombia

Resumen ANTECEDENTES: Las enfermedades respiratorias graves suelen afectar de manera desproporcionada a las mujeres embarazadas y representan un mayor riesgo de morbilidad y mortalidad materna y neonatal severas. Los informes clínicos de los desenlaces maternos y neonatales en mujeres embarazadas con COVID-19 siguen siendo escasos a pesar de la cantidad de información que surge a diario en la bibliografía universal. OBJETIVOS: Describir los desenlaces maternos y perinatales de las pacientes embarazadas con diagnóstico positivo de infección respiratoria aguda en la ciudad de Cartagena en el periodo de marzo a diciembre de 2020. MÉTODOS: Estudio observacional, descriptivo y transversal efectuado en mujeres embarazadas con diagnóstico positivo de infección por COVID-19. RESULTADOS: De las 120 participantes se excluyeron 70 por no tener diagnóstico confirmado por PCR para SARS-CoV-2. Se analizaron 50 pacientes con una mediana de edad de 29 años (RIC 24-32). El 30% requirió hospitalización, el 96% de las pacientes tuvo síntomas; el más frecuente fue la tos con un 50%, seguido de fiebre y anosmia con 42%. Las complicaciones maternas se registraron en el 28% de los casos, 14% requirieron atención en la UCI, además, el 6% de la muestra falleció. El 12% ameritó reanimación neonatal y el 24% se internó en la UCI. CONCLUSIONES: La mayoría tuvo síntomas respiratorios durante el ingreso, con una alta tasa de mortalidad materna. No se registraron desenlaces fatales en los neonatos.

Abstract BACKGROUND: Severe respiratory diseases tend to disproportionately affect pregnant women, representing an increased risk of severe maternal and neonatal morbidity and mortality. Clinical reports on maternal and neonatal outcomes in pregnant women with COVID-19 remain scarce despite the amount of information that emerges daily in the universal literature. OBJECTIVE: Describe the maternal and perinatal outcomes of pregnant patients with a positive diagnosis for acute respiratory infection COVID-19 in the city of Cartagena in the period between March and December 2020. METHODS: This was an observational, descriptive cross-sectional study was conducted including pregnant women with a positive diagnosis of COVID-19 infection in the city of Cartagena, between March 2020 and December 2020. RESULTS: Of the 120 participants, 70 were excluded for not having a diagnosis confirmed by PCR for SARS-CoV-2, 50 patients with a median age of 29 years (IQR 24 - 32) were analyzed, 30% required hospitalization, 96% of the patients presented symptoms, the most frequently referred being cough with 50%, followed by fever and anosmia with 42%. Maternal complications occurred in 28% of the cases, requiring admission to the ICU in 14%, and death occurred in 6% of the sample. 12% required neonatal resuscitation and 24% were admitted to the ICU. CONCLUSIONS: Most had respiratory symptoms during admission, with a high maternal mortality rate. There were no neonatal fatal outcomes.

Placental exosomes profile in maternal and fetal circulation in intrauterine growth restriction - Liquid biopsies to monitoring fetal growth.

INTRODUCTION: Placenta-derived exosomes may represent an additional pathway by which the placenta communicates with the maternal system to induce maternal vascular adaptations to pregnancy and it may be affected during Fetal growth restriction (FGR). The objective of this study was to quantify the concentration of total and placenta-derived exosomes in maternal and fetal circulation in small fetuses classified as FGR or small for gestational age (SGA). METHODS: Prospective cohort study in singleton term gestations including 10 normally grown fetuses and 20 small fetuses, sub-classified into SGA and FGR accordingly to birth weight (BW) percentile and fetoplacental Doppler. Exosomes were isolated from maternal and fetal plasma and characterized by morphology, enrichment of exosomal proteins, and size distribution by electron microscopy, western blot, and nanoparticle tracking analysis, respectively. Total and specific placenta-derived exosomes were determined using quantum dots coupled with CD63+ve and placental-type alkaline phosphatase (PLAP)+ve antibodies, respectively. RESULTS: Maternal concentrations of CD63+ve and PLAP+ve exosomes were similar between the groups (all p > 0.05). However, there was a significant positive correlation between the ratio of placental-derived to total exosomes (PLAP+ve ratio) and BW percentile, [rho = 0.77 (95% CI: 0.57 to 0.89); p = 0.0001]. The contribution of placental exosomes to the total exosome concentration in maternal and fetal circulation showed a significant decrease among cases, with lower PLAP+ve ratios in FGR compared to controls and SGA cases. DISCUSSION: Quantification of placental exosomes in maternal plasma reflects fetal growth and it may be a useful indicator of placental function.

Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes.

OBJECTIVE: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. METHODS: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes. RESULTS: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p = 0.001]. CONCLUSIONS: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.

A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes.

PROBLEM: The diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses. METHOD OF STUDY: AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined. RESULTS: (i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4-22; (P < 0.001); 70% (7/10) versus 35% (39/112); (P = 0.04); 1 (IQR: <1-2) days versus 25 (IQR: 5-51) days; (P = 0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). CONCLUSION: (i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.

Maternal plasma soluble TRAIL is decreased in preeclampsia.

OBJECTIVE: Preeclampsia (PE) is characterized by systemic intravascular inflammation. Women who develop PE are at an increased risk for cardiovascular disease in later life. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has anti-atherosclerotic effects in endothelial cells and can mediate neutrophil apoptosis. Low soluble TRAIL (sTRAIL) and high C-reactive protein (CRP) concentrations are associated with an increased risk of future cardiovascular disease in non-pregnant individuals. The aim of this study was to determine whether maternal plasma concentrations of sTRAIL and CRP differ between women with PE and those with uncomplicated pregnancies. METHOD: This cross-sectional study included women with an uncomplicated pregnancy (n = 93) and those with PE (n = 52). Maternal plasma concentrations of sTRAIL and CRP concentrations were determined by ELISA. RESULTS: 1) The median plasma sTRAIL concentration (pg/mL) was significantly lower and the median plasma CRP concentration was significantly higher in women with PE than in those with an uncomplicated pregnancy (25.55 versus 29.17; p = 0.03 and 8.0 versus 4.1; p = 0.001, respectively); 2) the median plasma concentration sTRAIL/CRP ratio was two-fold lower in women with PE than in those with an uncomplicated pregnancy (p < 0.001); and 3) women with plasma sTRAIL and CRP ratio in the lowest quartile were 8 times more likely to have PE than women with concentrations in the upper three quartiles (OR 8.9; 95% CI: 2.8-27.8). CONCLUSION: Maternal plasma sTRAIL concentrations are lower (while those of CRP are higher) in women with PE than in those with uncomplicated pregnancies. These findings are consistent with the evidence of intravascular inflammation in this disorder.

The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6.

OBJECTIVE: Intra-amniotic infection/inflammation are major causes of spontaneous preterm labor and delivery. However, diagnosis of intra-amniotic infection is challenging because most are subclinical and amniotic fluid (AF) cultures take several days before results are available. Several tests have been proposed for the rapid diagnosis of microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation. The aim of this study was to examine the diagnostic performance of the AF Mass Restricted (MR) score in comparison with interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8) for the identification of MIAC or inflammation. METHODS: AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n = 100). Intra-amniotic inflammation was defined as >100 white blood cells/mm(3) (WBCs) in AF; MIAC was defined as a positive AF culture. AF IL-6 and MMP-8 were determined using ELISA. The MR score was obtained using the Surface-Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry. Sensitivity and specificity were calculated and logistic regression models were fit to construct receiver-operating characteristic (ROC) curves for the identification of each outcome. The McNemar's test and paired sample non-parametric statistical techniques were used to test for differences in diagnostic performance metrics. RESULTS: (1) The prevalence of MIAC and intra-amniotic inflammation was 34% (34/100) and 40% (40/100), respectively; (2) there were no significant differences in sensitivity of the three tests under study (MR score, IL-6 or MMP-8) in the identification of either MIAC or intra-amniotic inflammation (using the following cutoffs: MR score >2, IL-6 >11.4 ng/mL, and MMP-8 >23 ng/mL); (3) there was no significant difference in the sensitivity among the three tests for the same outcomes when the false positive rate was fixed at 15%; (4) the specificity for IL-6 was not significantly different from that of the MR score in identifying either MIAC or intra-amniotic inflammation when using previously reported thresholds; and (5) there were no significant differences in the area under the ROC curve when comparing the MR score, IL-6 or MMP-8 in the identification of these outcomes. CONCLUSIONS: IL-6 and the MR score have equivalent diagnostic performance in the identification of MIAC or intra-amniotic inflammation. Selection from among these three tests (MR score, IL-6 and MMP-8) for diagnostic purposes should be based on factors such as availability, reproducibility, and cost. The MR score requires a protein chip and a SELDI-TOF instrument which are not widely available or considered "state of the art". In contrast, immunoassays for IL-6 can be performed in the majority of clinical laboratories.

Maternal floor infarction/massive perivillous fibrin deposition: a manifestation of maternal antifetal rejection?

OBJECTIVE: Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) are related placental lesions often associated with fetal death and fetal growth restriction. A tendency to recur in subsequent pregnancies has been reported. This study was conducted to determine whether this complication of pregnancy could reflect maternal antifetal rejection. METHODS: Pregnancies with MPFD were identified (n = 10). Controls consisted of women with uncomplicated pregnancies who delivered at term without MPFD (n = 175). Second-trimester maternal plasma was analyzed for panel-reactive anti-HLA class I and class II antibodies. The prevalence of chronic chorioamnionitis, villitis of unknown etiology, and plasma cell deciduitis was compared between cases and controls. Immunohistochemistry was performed on available umbilical vein segments from cases with MPFD (n = 4) to determine whether there was evidence of complement activation (C4d deposition). Specific maternal HLA-antibody and fetal HLA-antigen status were also determined in paired specimens (n = 6). Plasma CXCL-10 concentrations were measured in longitudinal samples of cases (n = 28 specimens) and controls (n = 749 specimens) by ELISA. Linear mixed-effects models were used to test for differences in plasma CXCL-10 concentration. RESULTS: (i) The prevalence of plasma cell deciduitis in the placenta was significantly higher in cases with MPFD than in those with uncomplicated term deliveries (40% versus 8.6%, P = 0.01), (ii) patients with MPFD had a significantly higher frequency of maternal anti-HLA class I positivity during the second trimester than those with uncomplicated term deliveries (80% versus 36%, P = 0.01); (iii) strongly positive C4d deposition was observed on umbilical vein endothelium in cases of MPFD, (iv) a specific maternal antibody against fetal HLA antigen class I or II was identified in all cases of MPFD; and 5) the mean maternal plasma concentration of CXCL-10 was higher in patients with evidence of MPFD than in those without evidence of MFPD (P < 0.001). CONCLUSION: A subset of patients with MPFD has evidence of maternal antifetal rejection.

Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsiaa.

OBJECTIVE: Preeclampsia (PE) can be sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined. METHODS: A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n=25); ii) late-onset PE (after 34 weeks, n=47); and iii) uncomplicated pregnancy (n=61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t-test (false discovery rate <0.1 and fold change >1.5), adjusting for maternal white blood cell count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n=31), late PE (n=72) and controls (n=99)] in all differentially expressed genes. Gene ontology analysis and pathway analysis were performed. RESULTS: i) 43 and 28 genes were differentially expressed in early- and late-onset PE compared to the control group, respectively; ii) qRT-PCR confirmed the microarray results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; iii) 20 genes that are involved in coagulation (SERPINI2), immune regulation (VSIG4, CD24), developmental process (H19) and inflammation (S100A10) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity (LTF, ELANE) and cell-to-cell recognition in the nervous system (CNTNAP3) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense (DEFA4, BPI, CTSG, LCN2), tight junctions in blood-brain barrier (EMP1) and liver regeneration (ECT2) were differentially expressed in both early- and late-onset PE. CONCLUSION: Early- and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early- and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE.

Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response.

OBJECTIVE: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS. METHODS: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration ≥ 17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay. RESULTS: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8-80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6-20.1 ng/mL; p < 0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1-75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9-23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman's Rho = 0.7, p < 0.0001). CONCLUSION: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.

Morbilidad materna extrema en cuidados intensivos obstétricos: Cartagena (Colombia) 2006 - 2008 / Maternal near miss in obstetric critical care: Cartagena, Colombia, 2006 - 2008

Objetivo: el presente estudio tiene como objetivo establecer la incidencia de la morbilidad materna extrema (MME), sus características clínicas y hacer una primera aproximación a los indicadores de calidad de la atención obstétrica en la unidad de cuidados intensivos (UCI). Materiales y métodos: estudio de cohorte, retrospectivo de pacientes obstétricas con MME que ingresaron a la UCI de la Clínica de Maternidad Rafael Calvo de Cartagena entre el período del 1 de enero de 2006 al 31 de diciembre de 2008. Se registraron las características sociodemográficas, ginecoobstétricas, criterios de MME y los indicadores de calidad de la atención obstétrica. Para el análisis de resultados se utilizaron medidas de tendencia central y dispersión, porcentajes, tablas de frecuencia y razones estandarizadas de morbilidad con intervalos de confianza (IC) al 95%. Resultados: la incidencia de MME fue de 12,1 por 1000 nacimientos. El 27,2% (88 pacientes) eran adolescentes y el 61,6% multigestantes (199 pacientes). El principal diagnóstico asociado a la MME fue el trastorno hipertensivo del embarazo, 49,5% (160 pacientes), seguido por las hemorragias del embarazo, 22,6% (73 pacientes). Las principales disfunciones orgánicas fueron respiratorias, 38,1% (123 casos), hepáticas, 15,2% (49 casos) e inmunológicas, 14,6% (47 casos). La transfusión fue la intervención más común, 22,6% (73 pacientes). Durante los años de estudio la incidencia de MME y la razón de casos de MME: muerte materna (MM) aumentaron, mientras que el índice de mortalidad disminuyó. Conclusiones: se encontró una incidencia de MME del 12,1 por 1000 nacimientos. Se presentaron los indicadores de calidad como medición basal, lo que servirá de comparación para futuras mediciones...

Objective: the present study aim to establish the incidence of severe maternal morbidity (SMM), the clinical characteristics and a first approximation to the quality indicators of the obstetric attention, of patients with SMM in the intensive care unit (ICU). Materials and methods: a retrospective cohort study of all consecutive obstetric admissions to the intensive care unit (ICU) in the Rafael Calvo maternity clinic in Cartagena, Colombia from January 1, 2006 to December 31, 2008. Sociodemographic and obstetric data, severe maternal morbidity (SMM) criteria and indicators to monitor quality of obstetric care were registered. The statistical analysis utilized measures of central tendency and spread, percentages, frequency tables and Standardized Morbidity Ratio (SMR) with an interval confidence of 95% (CI 95%). Results: the severe maternal morbidity incidence was 12.1 per 1000 deliveries. 27.2% of the population studied (88 patients) were teenagers and 61.6% were multiparous (199 patients). The most common diagnosis was hypertensive disorders of pregnancy (49.5%; 160 patients) followed by obstetric hemorrhages 22.6% (73 patients). The main dysfunctions were respiratory: 38.1% (123 patients), hepatic: 15.2% (49 patients) and immunological: 14.6% (47 patients). The most common intervention was transfusion, 22.6% (73 patients). During the study period the severe maternal morbidity incidence and the Maternal Near Miss mortality ratio increased, while the mortality index decreased...

Embarazo heterotópico: diagnóstico ecográfico temprano, manejo con laparoscopia: reporte de un caso y revisión de la literatura / Laparoscopic management of heterotopic pregnancy following ecographic diagnosis: a case report and literature review

Objetivo: realizar una revisión de la literatura acerca de los aspectos más importantes relacionados con el diagnóstico oportuno y el manejo del embarazo heterotópico. Materiales y métodos: se presenta un caso de un embarazo heterotópico diagnosticado por ultrasonografía, a quien se le realizó salpingectomía por laparoscopia y se continuó con la gestación intrauterina normal. Se realizó una revisión en las bases de datos MEDLINE y EMBASE, además de la base latinoamericana SciELO y libros de la especialidad. Conclusión: el diagnóstico del embarazo heterotópico es difícil debido a las diversas manifestaciones clínicas y a la existencia del embarazo intrauterino que continúa la producción de fracción Beta de la gonadotropina coriónica humana. La ecografía es un pilar importante en el diagnóstico e identificación temprana de esta patología. La laparoscopia surge como una alternativa segura en el manejo.

Objective: reviewing the pertinent literature about the most important aspects related to early diagnosis and management of heterotopic pregnancy. Materials and methods: a case of heterotopic pregnancy is presented which was diagnosed by ultrasonography. The patient underwent laparoscopic salpingectomy and she continued normal intrauterine gestation. MEDLINE and EMBASE databases were reviewed, as well as the Latin-American SciELO database and books on the specialization. Conclusion: diagnosis of heterotopic pregnancy is difficult due to its diverse clinical manifestations and intrauterine pregnancy leading to human chorionic gonadotropin Beta fraction production being continued; echography is thus an important pillar in the early diagnosis and identification of this pathology. Laparoscopy emerges as a safe management alternative.