Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Endometrial Progesterone and Estrogen Receptors in Relation to Hormonal Levels in Women with Unexplained Recurrent Miscarriage / Receptores endometriais de progesterona e estrogênio em relação aos níveis hormonais em mulheres com aborto recorrente inexplicável

Abstract Objective Recurrent miscarriage has been linked to hormonal disturbance due to dysregulation of its receptors rather than to the availability of the hormone. We aimed to investigate endometrial expression of progesterone and estrogen receptors in relation to serum and endometrial hormonal levels in unexplained recurrent miscarriage. Methods The present case control study included 20 cases with unexplained recurrent miscarriage and 20 parous women as controls. Ovulation was confirmed using an ovulation kit and 10 to 12 days after detecting the urinary luteinizing hormone surge, all women were subjected to a blood sample and to an endometrial biopsy. Progesterone and estrogen levels were measured in serum and in endometrial tissue and receptor concentrations were in the endometrial sample. Results Women with recurrent miscarriage showed significantly lower concentration of receptors in both the cytoplasm and the nucleus of endometrial tissue compared with controls. The nuclear/cytoplasm ratio of progesterone receptor was significantly higher in cases compared with controls, implicating that recurrent miscarriage is probably linked to nongenomic activity of the hormone; this was also significant for estrogen receptor. Serum progesterone and estrogen hormonal levels were comparable between groups while both hormones were significantly reduced in the endometrium of recurrent miscarriage cases. Receptors significantly correlated with endometrial hormonal level but not to serum level. Conclusion Recurrent miscarriage might be linked to reduced endometrial progesterone and estrogen receptors and appears to be more related to nongenomic activity of progesterone. Endometrial receptors expression correlates to tissue hormonal level rather than to serum hormonal level.

A Rare Case of Factor Xii Deficiency in a Pregnant Woman

@#Factor XII deficiency, also known as the Hageman factor, is a rare disorder that has not been associated with any adverse outcomes. It is an interesting blood disorder whereby in the state of deficiency, it causes prolongation activated partial thromboplastin time (aPTT) which is correctable with mixing test. Although there have been case reports that have mentioned events of thrombosis and bleeding, however, no clear causal relationship has been established. Evidence for adverse events occurring in patients with Factor XII deficiency is sparse. We report here a case of a lady with a history of miscarriages who was incidentally found to have Factor XII deficiency during a routine workup for prolonged aPTT.

Role of serum anti mullerian hormone as a predictor for miscarriage

Background: Recurrent Miscarriage is defined as three or more failed clinical pregnancies at less than 20 weeks of gestation or fetal weight less than 500 grams that ends spontaneously. Ovarian reserve demonstrates reproductive potential and includes FSH, estradiol, inhibin B, and S. AMH levels. Women with very low AMH levels may have altered folliculogenesis that may influence early implantation to increase the risk of miscarriage. This study aimed to determine the serum AMH levels in patients with recurrent miscarriage and pregnancy outcomes in low (<1 ng/ml), normal (1-3.5 ng/ml) and high (>3.5 ng/ml) AMH groups and to evaluate the role of serum ovarian biomarkers in prediction of miscarriages.Methods: This was a case-control study conducted over a time period of 1 year, on 120 women attending the antenatal clinic in department of obstetrics and gynecology, Swaroop Rani Nehru Hospital, Prayagraj. The patients were divided into two groups, Group 1 (n=80) included women with previous history of abortions and Group 2 (n=40) included women with no history of abortions. S. AMH levels were analyzed and compared in both the groups.Results: In the present study, a significant negative correlation was seen between S. AMH and rate of miscarriages (p <0.05). Low AMH values were observed in patients with history of previous pregnancy loss.Conclusions: Diminished ovarian reserve contributes to recurrent pregnancy loss and should be considered part of the work-up for RPL. AMH levels in recurrent miscarriage patients were lower than those in a normal population.

Conceptos básicos en inmunología de la reproducción: revisión narrativa de la bibliografía / Basic concepts in reproductive immunology: a narrative review of the literature

Resumen: ANTECEDENTES: La inmunología de la reproducción no es un área nueva: siempre ha estado relacionada con el aborto recurrente y con la falla repetida en la implantación, sobre todo en el contexto de una fertilización in vitro. Recientemente emergieron nuevos conceptos importantes que los ginecoobstetras deben considerar. OBJETIVO: Interrelacionar los conceptos básicos de inmunología, embriología y reproducción asistida para comprender mejor lo que la primera puede resolver y lo que no. METODOLOGÍA: Estudio retrospectivo efectuado con base en la búsqueda electrónica, llevada a cabo en febrero de 2020 en las bases de datos: PubMed y Google Scholar con los siguientes términos (MeSH): abortion, spontaneous/immunology; embryo implantation/immunology; HLA-c antigens/immunology; immune tolerance/immunology; immunity, maternally-acquired/immunology; uterus/immunology; killer cells, natural/immunology; placentation/immunology; receptors, kir/immunology; antigen presentation/genetics; antigen presentation/immunology; maternal-fetal exchange/genetics; maternal-fetal exchange/immunology. RESULTADOS: Se reunieron 289 artículos y se eliminaron 248 por no cumplir con los criterios de inclusión; solo se analizaron 41. Los artículos identificados sirvieron de base para actualizar la situación de la inmunología en el contexto de la medicina de la reproducción. Durante el proceso se revisaron otros artículos que sirvieran de soporte bibliográfico a los conceptos descritos en esta revisión. CONCLUSIONES: Debido al destacado interés en el estudio de la genética de los embriones, la medicina de la reproducción se enfocó más en ella y dejó de lado a la inmunología. Sin embargo, como la genética sigue sin poder explicar de manera adecuada las fallas en la implantación, la inmunología de la reproducción vuelve a cobrar impulso.

Abstract: BACKGROUND: Reproductive immunology is not a new area in reproductive medicine, it has always been related to recurrent miscarriage and repeated implantation failure, especially in the context of IVF. Recently, new concepts have emerged that are important for OBGYN specialists to keep in mind. OBJECTIVE: Interrelating the basic concepts of immunology, embryology and assisted reproduction to better understand what the former can and cannot solve. METHODOLOGY: Retrospective study based on the electronic search, carried out in February 2020, in the databases: PubMed and Google Scholar with the following terms (MeSH) The following MeSH terms were used: Abortion, Spontaneous/immunology; Embryo Implantation/immunology; HLA-C Antigens/immunology; Immune Tolerance/immunology; Immunity, Maternally-Acquired/immunology; Uterus/immunology; Killer Cells, Natural/immunology; Placentation/immunology; Receptors, KIR/immunology; Antigen Presentation/genetics; Antigen Presentation/immunology; Maternal-Fetal Exchange/genetics; Maternal-Fetal Exchange/immunology. RESULTS: 289 articles were collected, and 248 articles were deleted because they did not meet the inclusion criteria; only 41 were analyzed. The articles identified served as a basis for updating the status of immunology in the context of reproductive medicine. During the process, other articles were reviewed to serve as bibliographic support for the concepts described in this review. CONCLUSIONS: Due to the outstanding interest in the study of embryo genetics, reproductive medicine focused more on it and left immunology aside. However, since genetics still cannot adequately explain implantation failures, reproductive immunology is gaining momentum again.

Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects

Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.

Pérdida recurrente del embarazo e hipertensión pulmonar idiopática / Recurrent pregnancy loss and idiopatic pulmonary hypertension

Resumen La pérdida recurrente del embarazo ocurre cuando una mujer tiene 2 ó más pérdidas de embarazos clínicos antes de las 20 semanas de gestación. Existen múltiples factores de riesgo relacionados con este padecimiento, entre ellos, la presencia de Hipertensión Pulmonar (HP) se vincula con elevada mortalidad (30-56% de los casos) y riesgo de abortos entre las semanas 9 y 12 de gestación. No se conoce con precisión la frecuencia de asociación entre las condiciones clínicas referidas. Presentamos el caso de una mujer de 31 años de edad que ingresó al hospital con un aborto en evolución, en el periodo posterior al legrado evidencian Hipoxemia Grave e Insuficiencia Cardiaca Derecha; durante el abordaje diagnóstico se confirma que la causa primaria de la recurrencia de abortos se encuentra asociada con la presencia de Hipertensión Pulmonar Idiopática.

Abstract Recurrent pregnancy loss occurs whenever a woman has 2 or more miscarriages of their clinical pregnancy before 20 weeks of gestation. There are multiple risk factors relates to this condition, among, them, the presence of pulmonary hypertension (PH) is linked with high mortality (30-56% of cases) and risk of miscarriages between 9 weeks and 12 of gestation. The prevalence of both conditions are not well known. Here, we present the case of a 31 year-old women who was admitted to the hospital with an abortion in evolution, immediately after the curettage, the patient exhibit severe hypoxemia in association with Right Heart Failure; the medical approach established that the primary cause of recurrent abortions was an uncontrolled idiopathic pulmonary hypertension.

Effect analysis of nursing intervention on patients with recurrent abortion treated with progesterone / 中国生化药物杂志

Objective To investigate recurrent spontaneous abortion patients received bends the clinical application effect of nursing intervention during progesterone treatment. Methods Two patients with recurrent spontaneous abortion group were treated with progesterone treatment, the control group in the conventional nursing service only provides flexor progesterone treatment on the basis of comprehensive nursing service study group progesterone treatment on the basis of routine the combination of nursing and nursing intervention in the 2 groups of patients with recurrent spontaneous abortion. The success rate of pregnancy were recorded, the rate of abortion, the data will be given the statistical analysis (using SPSS software) after the conclusion. Results The study group of patients with recurrent spontaneous abortion pregnancy success rate (95.45%) and control group (90.91%) there is no significant difference between the study group of patients with recurrent spontaneous abortion abortion rate (6.82%) was significantly lower than the control group (34.09%), there was significant difference between the groups, P<0.05. Conclusion Recurrence During the treatment of flexor progesterone abortion were given routine nursing and nursing intervention combined with the comprehensive clinical nursing service can obtain ideal success rate of pregnancy, to reduce the rate of abortion is also of positive significance, is conducive to the protection of patients' quality of life, physical and mental health.

Clinical analysis of low molecular weight heparin calcium combined with psychological intervention in treatment of recurrent spontaneous abortion / 中国生化药物杂志

Objective To explore the clinical effect of low molecular weight heparin calcium combined with psychological intervention in the treatment of recurrent spontaneous abortion. Methods 60 patients were treated with recurrent miscarriage after treatment in our hospital from October 2016 to June 2017, and these patients were randomly divided into two groups: control group and observation group.Each group of 30 cases. First of all, the two groups of patients were treated with low molecular weight heparin calcium, and then the control group of patients to choose the most commonly used care methods for nursing operations,the observation group of patients choose to use more targeted psychological intervention care for nursing work.The clinical effects of the two groups were observed and compared. Results There was no significant difference between the two groups. The adverse reaction rate was 10.00% in the observation group and the control group The adverse reaction rate was 26.67%. The adverse reaction rate of the observation group was significantly lower than that of the control group.The difference between the two groups was statistically significant (P<0.05). Conclusion Recurrence of recurrent miscarriage after treatment of patients with more targeted psychological intervention in nursing care,compared to conventional care methods better,while effectively reducing the low molecular weight heparin calcium treatment of recurrent miscarriage of adverse reactions.The incidence of psychological intervention in the care of the clinical way is a worthy of use and to promote the treatment.

Clinical analysis of low molecular weight heparin calcium combined with psychological intervention in treatment of recurrent spontaneous abortion / 中国生化药物杂志

Objective To explore the clinical effect of low molecular weight heparin calcium combined with psychological intervention in the treatment of recurrent spontaneous abortion. Methods 60 patients were treated with recurrent miscarriage after treatment in our hospital from October 2016 to June 2017, and these patients were randomly divided into two groups: control group and observation group.Each group of 30 cases. First of all, the two groups of patients were treated with low molecular weight heparin calcium, and then the control group of patients to choose the most commonly used care methods for nursing operations,the observation group of patients choose to use more targeted psychological intervention care for nursing work.The clinical effects of the two groups were observed and compared. Results There was no significant difference between the two groups. The adverse reaction rate was 10.00% in the observation group and the control group The adverse reaction rate was 26.67%. The adverse reaction rate of the observation group was significantly lower than that of the control group.The difference between the two groups was statistically significant (P<0.05). Conclusion Recurrence of recurrent miscarriage after treatment of patients with more targeted psychological intervention in nursing care,compared to conventional care methods better,while effectively reducing the low molecular weight heparin calcium treatment of recurrent miscarriage of adverse reactions.The incidence of psychological intervention in the care of the clinical way is a worthy of use and to promote the treatment.

Intravenous immunoglobulin G in women with reproductive failure: The Korean Society for Reproductive Immunology practice guidelines / 대한생식의학회지

The task force of the Korean Society for Reproductive Immunology recommends intravenous immunoglobulin G treatment in women with reproductive failure, including recurrent pregnancy loss and/or repeated implantation failure, who show cellular immune factors such as abnormal natural killer cell levels, natural killer cell cytotoxicity, and/or type 1 T helper immunity.

Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization / 대한생식의학회지

OBJECTIVE: To describe in vitro development of human embryos derived from an individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect. METHODS: A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, in vitro fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening. Findings in NLRP7 were recorded and embryo culture and biopsy data were tabulated as a function of parental origin for any identified ploidy error. RESULTS: The patient was found to have a pathogenic variant in NLRP7 (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10 embryos were available after fertilization via intracytoplasmic sperm injection. Developmental arrest was noted for all 10 embryos after 144 hours in culture, thus no transfer was possible. These non-viable embryos were evaluated by karyomapping and all were diploid biparental; two were euploid and eight had various aneuploidies all of maternal origin. CONCLUSION: This is the first report of early human embryo development from a patient with any NLRP7 mutation. The pathogenic variant identified here resulted in global developmental arrest at or before blastocyst stage. Standard IVF should therefore be discouraged for such patients, who instead need to consider oocyte (or embryo) donation with IVF as preferred clinical methods to treat infertility.

Expression of E2A in Mid-secretory Endometrium of Women Suffering from Recurrent Miscarriage / 华中科技大学学报（医学）（英德文版）

E2A is involved in promoting forkhead box P3 (FOXP3) and retinoid-related orphan receptor gamma t (RORγt) gene transcription,which are pivotal transcription factors of T regulatory cells and Thl7 cells,respectively.Little is known about the involvement of E2A in pregnancy process.This study aimed to investigate the expression of E2A,cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage (RM) (n=21) and control group (n=11) by immunohistochemistry,with the Vectra(R) automated quantitative pathology imaging system for analysis.The percentage of E2A+ cells and CTLA-4+ cells was significantly higher in the endometrium of women with RM than in the controls.There was positive correlation between E2A and CTLA-4 (r=0.523,P=0.002),E2A and FOXP3 (r=0.380,P=0.032),and FOXP3 and CTLA-4 (r=0.625,P=0.000) in the mid-secretory phase of endometrium for all subjects.It was concluded that the abnormal expression of endometrial E2A existed in mid-secretory endometrium of women with RM,and there was a positive correlation between E2A and FOXP3,and E2A and CTLA-4,suggesting the possible regulation role of E2A involved in regulating endometrium receptivity.

A healthy delivery of twins by assisted reproduction followed by preimplantation genetic screening in a woman with X-linked dominant incontinentia pigmenti / 대한생식의학회지

The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The patient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful pregnancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages.

Aborto recurrente de etiología aloinmune / Alloimmune recurrent spontaneous abortion

Los mecanismos que subyacen la reproducción humana son muy complejos, por lo que cualquier pérdida gestacional implica el tener que considerar diversas etiologías, más aun si se trata de pérdidas gestacionales recurrentes dentro de las que la inmunidad juega un papel especialmente importante. Desde hace varias décadas, el factor aloinmune ha sido reconocido como un desencadenante frecuente de la interrupción del embarazo, haciéndose de esta forma relevante su estudio en mujeres con aborto recurrente. En el presente artículo, a partir de una búsqueda sistemática de información, se revisan con detalle los aspectos relacionados con la fisiopatología, el diagnóstico y el tratamiento del aborto recurrente de etiología aloinmune, buscando con esto sensibilizar al profesional de la salud sobre su consideración ante una mujer con pérdida recurrente de la gestación.

The mechanisms underlying the human reproduction are very complex, so any pregnancy loss implies the need of considering various etiologies, even more if those pregnancy losses are recurrent within which the immunity plays an important role. Since decades, the alloimmune factor has been recognized as a frequent trigger of the pregnancy interruption, thus becoming relevant its study in women with recurrent miscarriage. In the present article, through a systematic search of information, details concerning to the physiopathology, diagnosis and treatment of the recurrent miscarriage of alloimmune etiology are reviewed, looking to sensitize the health professional about its consideration when evaluating a woman with recurrent pregnancy loss.

Relationship between expression of COX-2, TNF-α, IL-6 and autoimmune-type recurrent miscarriage

OBJECTIVE@#To investigate the roles of COX-2, TNF-α, IL-6 in the pathogenesis of autoimmune-type recurrent spontaneous abortion (RSA).@*METHODS@#RT-PCR was used to detect the mRNA of COX-2, TNF-α, IL-6 in the trophoblast cells of murine RSA and normal pregnant models. The COX-2, TNF-α, IL-6 protein expressions were determined by using immunohistochemisry staining method. The COX-2, TNF-α, IL-6 protein expressions were determined by ELISA.@*RESULTS@#The embryo loss rates in experiment group was significantly higher than that in normal pregnancy control group, the expression of COX-2, TNF-α, IL-6 in the trophoblast cells of murine RSA and normal pregnant models. The expression of COX-2 in autoimmune-type recurrent spontaneous abortion was significantly lesser than in normal pregnant models. The expression of TNF-α, IL-6 in autoimmune-type recurrent spontaneous abortion was significantly higher than in normal pregnant models. There was a positively correlation between TNF-α and IL-6. There was no relationship between COX-2, TNF-α and IL-6.@*CONCLUSIONS@#The abnormal expression of COX-2, TNF-α and IL-6 may result in RSA.

Importancia de alteración cromosómica en parejas, como causa de aborto recurrente: revisión sistemática de la literatura / Chromosomal alterations in couples with recurrent miscarriage: systematic review of the literature

Objetivo: Determinar la frecuencia de alteraciones genéticas en uno o ambos progenitores de parejas con aborto recurrente. Método: Se buscaron artículos en inglés en las bases de datos MEDLINE y PUBMED entre los años 1990 y 2013 que reportaran estudio de cariograma en parejas con aborto recurrente y que no se hubieran sometido a técnicas de reproducción asistida. Resultados: La frecuencia de alteraciones cromosómicas fue variable en los distintos trabajos analizados con variaciones importantes en el número de pacientes incluidos. Aunque los trabajos analizados usaron diferentes números para definir el aborto recurrente, no hubo diferencias en la frecuencia de alteraciones genéticas al considerar 2 o más abortos versus 3 o más. La translocación recíproca fue la alteración más frecuentemente encontrada. Las alteraciones cromosómicas fueron más frecuentes en mujeres que en hombres. Conclusión: El análisis cromosómico es fundamental en el estudio de las parejas con aborto recurrente. En aquellas parejas portadoras de alguna alteración, es esencial que se realice un consejo genético adecuado y se debe sugerir la realización de diagnóstico prenatal en embarazos futuros.

Objective: To determine the frequency of genetic alterations in couples with recurrent miscarriage. Methods: We searched articles in English in MEDLINE and PUBMED databases between 1990 and 2013, which reported karyotype analysis in couples with recurrent miscarriage and that had not been subjected to assisted reproduction techniques. Results: The frequency of chromosomal alterations differ among different studies, furthermore we found a significant variation in the number of patients included. Although articles studied used different numbers to define recurrent miscarriage, there were no significant differences in the frequency of genetic alterations among couples with at least 2 or at least 3 miscarriages. The reciprocal translocation alteration was the most frequently found genetic alteration. Chromosomal alterations were more frequent in women. Conclusion: Chromosomal analysis is essential in the study of couples with recurrent miscarriage. In those couples carriers of some alteration, is essential to perform a genetic counseling and should be offered prenatal diagnosis in future pregnancies.

Combined Hysteroscopy and Laparoscopy in the Evaluation of Patients with Recurrent Pregnancy Loss

To determine the relative frequency of gynecological pathologies in patients with recurrent pregnancy loss using combined hysteroscopy and laparoscopy, and to evaluate the potential of this combined strategy in the diagnosis of coexisting pathologies. Methods: Over 6 years, in a large referral infertility clinic and research centre in Tehran, 80 women with the diagnosis of recurrent pregnancy loss underwent hysteroscopy and laparoscopy. Results: Forty nine (61.3%) women had 3 episodes of miscarriage, 9 (11.3%) had 4 occurrence of pregnancy loss and 14 (17.5%) patients had experienced 5 abortions. Also, there were 4 (5%), 2 (2.5%) and 2 (2.5%) participants with 6, 7 and 8 miscarriages, respectively. Thirteen women (16.2%) had normal hysteroscopy, and in 52 (65%) participant's laparoscopy did not reveal abnormal findings. Septate uterus and submucous myomas together, comprised 62 (77.5%) of the recognized pathologies in hysteroscopy. Of the 28 abnormalities found in laparoscopy, 12 (43%) was endometriosis (15% overall) and the others were, pelvic and abdominal adhesions. Conclusion: Combined laparoscopy and hysteroscopy yields more satisfactory diagnostic results compared with hysteroscopy alone. Septate uterus, submucous myomas and endometriosis were common findings in patients with recurrent miscarriage. Especially, patients with recurrent pregnancy loss should be examined for the coexistence of endometriosis.

Efecto de los anticuerpos antifosfolipídicos en la formación y degradación de la malla de fibrina en pacientes con aborto recurrente / Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage

En el presente trabajo se estudió el proceso de formación y disolución de la malla de fibrina y la generación de plasmina en un grupo de pacientes con aborto recurrente (AR) debido a la presencia de anticuerpos antifosfolipídicos (N= 10), mujeres con AR sin el síndrome antifosfolipídico (SAF) (N= 6) y se comparó con un grupo de mujeres sanas (N= 8). Del grupo de pacientes estudiadas con SAF, nueve fueron positivas para anticuerpos anticardiolipina (aCL), cinco para la anti-b2-glicoproteína I (anti-b2GPI), cuatro para ambos anticuerpos, una para anticuerpos antiprotrombina (aPT) y anticoagulante lúpico (AL). El proceso de formación de la fibrina y su disolución fue estudiado por turbidimetría y la generación de plasmina mediante sustrato cromogénico S2251. Las curvas de polimerización de la(s) paciente(s) con AR sin SAF y AL presentaron un incremento en la pendiente y turbidez final, comparado con las del grupo control de mujeres sanas. La velocidad de disolución del coágulo fue mayor en la paciente con AL (21 ± 0) 10-4 DDO/seg y en las AR sin SAF (19,6 ± 5,7) 10-4 DDO/seg, comparado con el grupo control (14,5 ± 2,8) 10-4 DDO/seg. La generación de plasmina estuvo incrementada solamente en las AR sin SAF (85 ± 24%) comparado con 52 ± 3% en el grupo control, p= 0,005. Los cambios observados en el proceso de polimerización y fibrinólisis de la(s) paciente(s) con AR sin SAF y AL pudieran estar relacionados con el incremento en los niveles de fibrinógeno, mientras que los de la generación de plasmina con la entidad mórbida.

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N= 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N= 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-b2-glycoprotein I (anti-b2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 ± 0) 10-4 DOD/seg and the RM patients without APS (19.6 ± 5.7) 10-4 DDO/seg, compared to that of the control group (14.5 ± 2.8) 10-4 DDO/seg. Plasmin generation increased only in RM patients without APS (85 ± 24%) against the control group (52 ± 3%), p= 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients´ morbidity.

Aborto recurrente / Recurrent pregnancy loss

Aproximadamente 1-3 por ciento de parejas en edad reproductiva experimentan 3 ó más abortos espontáneos consecutivos, lo que se define como aborto recurrente. La evaluación debe incluir una detallada historia clínica y examen físico, seguida de una serie de exámenes protocolizados destinados a detectar los factores más frecuentemente involucrados en esta patología (anatómico, cromosómico, inmunológico, endocrinológico y trombofílico). El manejo debe basarse en evidencias, evitando tratamientos experimentales o sin sustento científico, e incluyendo siempre un adecuado soporte emocional, tan necesario en estas parejas. A pesar de los esfuerzos por dilucidar los orígenes del aborto recurrente, sigue existiendo un 50 por ciento de casos sin causa aparente, los cuales suelen lograr tasas de embarazo exitoso de hasta 70 por ciento sin mediar tratamiento médico alguno.

Approximately 1-3 percent of reproductive age couples experience3 or more consecutive pregnancy losses, which is known as recurrent pregnancy loss. The evaluation must include a detailed clinical history and physical examination, followed by a diagnostic screening protocol in order to detect the most frequent factors involved in this disorder (anatomic, chromosomic, immunologic endocrinologic and thrombophilic). Management must be evidenced based, avoiding experimental or unproven treatments, and always including an adequate emotional support, so necessary for these couples. In spite of every effort made to find out the origins of recurrent pregnancy loss, 50 percent of couples remain with unknown diagnosis, however, they may reach up to 70 percent of successful future pregnancies even without medical treatment.