Early Spontaneous Miscarriage Research Articles

Sperm morphology by strict criteria does not predict clinical pregnancy rate following intra-uterine insemination

ABSTRACT Objective To determine the impact of abnormal sperm morphology of the pre-washed semen sample on the day of intrauterine insemination (IUI) on clinical pregnancy rates (CPR) Design Cross sectional retrospective chart review. Setting Academic fertility center Patient(s) Couples undergoing (IUI) from May 2014 to March 2022. Intervention(s) Sperm morphology, by strict criteria, on the pre-washed IUI sample. Main outcomes Measure(s) To determine the association of sperm morphology with CPR. Result(s) Semen analysis reports, including Kruger strict criteria for morphology from the pre-washed IUI sample, were reviewed for 1,059 cycles, comprising 825 total treated couples. Of the total 1,059 cycles,15.1% resulted in clinical pregnancy. When categorized by strict morphology ≥4% (normal morphology), (3%–2%) [mild-moderate teratozoospermia (TZS)], and ≤1% (severe TZS), the CPR was 16%, 13%, and 10%, respectively (p value 0.30). Early spontaneous miscarriage rate was 4% and when stratified by morphology ≥4% (3%–2%), and ≤1%, was 3%, 1%, and 0%, respectively (p value 0.20). In couples with isolated TZS, the pregnancy rate was 16% in the normal morphology group, 14% in the mild–moderate group, and 8% in the severe group. (p value 0.30). In the multivariate logistic regression, sperm morphology, mild/moderate TZS vs normal forms (OR = 0.99, 95% CI [0.94–1.1]), severe TZS vs normal forms (OR = 0.98, 95% CI [0.0.83–1.1]), was not a predictor of CPR. The Pre-wash TMSC (OR = 1.0, 95% CI [0.996–1.00]) was also not predictive of CPR. The only predictive factor of CPR in IUI was the PWTMSC (OR = 1.03, 95%CI [1.00–1.06). Conclusion(s) The morphology of the pre-washed sample on the day of IUI did not find a difference in CPR, neither in miscarriage rate following IUI, in couples with normal or abnormal sperm morphology, including severe TZS. Mild, moderate, or severe TZS in the semen sample should not exclude couples to attempt an IUI procedure.

Genetic analysis of chorionic villus tissues in early missed abortions

Chromosomal abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology for genetic diagnosis of early missed abortion tissues. Chromosome analysis of 1191 abortion CVSs in early pregnancy was conducted from August 2016 to June 2021; 463 cases were conducted via copy-number variations sequencing (CNV-seq)/quantitative fluorescent-polymerase chain reaction (QF-PCR) and 728 cases were conducted using SNP array. Clinically significant CNVs of CVSs were identified to clarify the cause of miscarriage and to guide the couples’ subsequent pregnancies. Among these, 31 cases with significant maternal cell contamination were removed from the study. Among the remaining 1160 samples, 751 cases (64.7%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 54 (4.7%) were partial aneuploidies, 77 (6.6%) had submicroscopic CNVs (including 25 with clinically significant CNVs and 52 had variants of uncertain significance), and 8 cases (0.7%) were uniparental disomies. Our study suggests that both SNP array and CNV-seq/QF-PCR are reliable, robust, and high-resolution technologies for genetic diagnosis of miscarriage.

Clinical assessment of the placenta function in women at risk and threat of premature delivery

Premature birth, despite the significant achievements of perinatal medicine in recent decades, remains an urgent global and national medical and social problem, as it is the leading cause of perinatal morbidity and mortality. According to modern views, placental dysfunction can be one of the causes of premature birth, and its frequency, according to randomized studies, can be from 78 to 91%, depending on the gestational age. At the same time, the research conducted to date does not provide a clear understanding of the role of timely diagnosis and prevention of placental dysfunction in preventing premature birth.The objective: to perform clinical evaluation of the prevalence of placental dysfunction in women at risk of preterm birth and with threat of preterm birth.Materials and methods. 180 pregnant women were took part in the study. To achieve the research aim, three research groups were formed. I group – 73 pregnant women with threat of premature birth; II group – 77 pregnant women with risk factors for premature birth. Women with risk factors for premature birth were included in the study at the stage of pregnancy planning (IIA subgroup, 39 women) or from the moment of applying to a women’s outpatient clinic to monitor the course of pregnancy (IIB subgroup, 38 pregnant women). The control group included 30 pregnant women with an uncomplicated course of pregnancy.Transabdominal ultrasound examination with color Doppler mapping, determination of free estriol, progesterone and placental lactogen levels in blood serum were performed at 18–21+6 and 28–30 weeks of gestation.Results. Analysis of the prevalence of risk factors for placental dysfunction and preterm birth in patients of the studied cohort showed that in pregnant women with preterm birth (I group), the combination of risk factors was 5.2; in pregnant women who received pre-gravid training (IIA subgroup) – 3.2; in pregnant women who were included in the study in the I trimester of pregnancy (IIB subgroup) – 4.7, while in pregnant women of the control group – only 0.8 (p<0.05).The threat of early spontaneous miscarriage with the formation of a retrochorial hematoma as a clinical manifestation of primary placental dysfunction was determined in 43.8% of pregnant women whose premature delivery was carried out for medical reasons. Placenta abruption in these patients can be considered as decompensation of the primary dysfunction of the placenta with the transition to acute placental insufficiency.The formation of chronic placental dysfunction, clinically manifested by the syndrome of fetal growth retardation, was most often observed in patients whose pregnancy ended in spontaneous premature birth at 34–36+6 weeks in the presence of an untouched amnion, – 68.6% compared to births at 28–33+6 weeks of gestation – 25.9% and with childbirth at 22–37+6 weeks – 13.3%.Conclusions. Clinical manifestations of placental dysfunction were detected in 30.6% of patients with premature birth, with morphological signs in 60.4% of cases, which indicates the hidden course of placental insufficiency before the development of premature birth.Morphological signs of placental dysfunction were determined in 87.5% of cases of premature births for medical reasons and in 100.0% of cases of spontaneous births at 22–27+6 weeks of gestation (with a combination of risk factors from 2.1 to 3.0), in 66.7% – with premature births at 28–33+6 weeks of pregnancy, in 40.0% – with premature births at 34–36+6 weeks of pregnancy and only in one (5.6%) case – with term births.The frequency of fixation of morphological characteristics of placental dysfunction correlates with the frequency of early pregnancy complications, primarily with the formation of retrochorial hematomas in the first half of pregnancy.

Association between ovarian reserve and spontaneous miscarriage and their shared genetic architecture.

Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data? Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways. Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data. Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis. There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause. In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P < 0.001), 1.62 times for antral follicular count <5 (P < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13-1.49, P < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways. The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population. Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities. This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25-28 June 2023 (Poster number: P-477). The authors declare no conflict of interest. N/A.

Endometrial thickness and early pregnancy complications after frozen-thawed embryo transfers.

The relationship between endometrial thickness and pregnancy safety after in vitro fertilization treatment is an important topic that should provoke attention. The aim of this study was to demonstrate the relationship between endometrial thickness on day of embryo transfer and early pregnancy complications, including ectopic pregnancy and early miscarriage, in frozen thawed embryo transfer (FET) cycles. Patients undergoing their first FET cycles were included into this study from January 2010 to December 2021. Patients were divided into three groups according to endometrial thickness on day of embryo transfer: Thin, ≤ 7mm; Medium, 7-14mm; Thick, ≥ 14mm. Ectopic pregnancy and early miscarriage were the two primary outcomes. Endometrial thickness was the main measured variable. The risk factors of these two compilations were determined based on univariate analysis and multivariate logistic regression analysis. A total of 11138 clinical pregnancies were included. The overall ectopic pregnancy and early spontaneous miscarriage rates were 2.62% and 13.40%. The ectopic pregnancy and early spontaneous miscarriage rates were significantly higher in patients with thin endometrium as compared with those in the other two groups (ectopic pregnancy rate: 5.06% vs. 2.62% vs. 1.05%; P < 0.001; early spontaneous miscarriage rate: 15.18% vs. 13.45% vs. 11.53%; P < 0.001). In multivariate logistic regression analysis, thin endometrium was an independent factor to predict ectopic pregnancy [adjusted odds ratio (aOR): 5.62; 95% confidence interval (CI): 2.51-12.58, P < 0.001], and to predict early spontaneous miscarriage rate (aOR: 1.57; 95% CI: 1.21-1.74, P < 0.001). Thin endometrium on day of embryo transfer in FET cycles is an independent predictor for early pregnancy compilations, including ectopic pregnancy and early spontaneous miscarriage.

Polycystic ovary syndrome increases the rate of early spontaneous miscarriage in women who have undergone single vitrified euploid blastocyst transfer

Research questionDoes polycystic ovary syndrome (PCOS) independently influence the risk of early spontaneous miscarriage in patients undergoing single euploid vitrified blastocyst transfer? DesignThis observational cohort study retrospectively analysed 1498 patients undergoing their first single euploid blastocyst frozen transfer cycles between October 2016 and December 2021. Patients were divided into PCOS and non-PCOS groups according to the Rotterdam criteria. Logistic regression analysis was conducted to study the independent effect of maternal PCOS status on early spontaneous miscarriage after single euploid embryo transfer after adjusting for confounding factors. ResultsNo statistically significant differences were identified in the rates of positive pregnancy test (68.95% versus 64.86%, P = 0.196) or clinical pregnancy (59.93% versus 57.33%, P = 0.429) between the PCOS and non-PCOS groups after single euploid embryo transfer. Early spontaneous miscarriage occurred more frequently in women with PCOS compared with controls (18.67% versus 12.00%, P = 0.023). In single euploid embryo transfer cycles, PCOS significantly increased the incidence of early spontaneous miscarriage after adjusting for some potential confounders (adjusted odds ratio 1.649, 95% CI 1.032 to 2.635, P = 0.036). ConclusionsAlthough no significant difference was observed in clinical pregnancy rates, PCOS status increased the risk of early spontaneous miscarriage after single vitrified euploid blastocyst transfer, suggesting an additional role of endometrial dysfunction affected by endocrine disorders. Further studies are needed to investigate the specific mechanisms and effective intervention strategies.

The Natural History of Fetal Triploidy in an Era of Limited Abortion Access: A Case Series [ID: 1380133

INTRODUCTION: Triploidy is a chromosomal abnormality that occurs in 1–3% of all conceptions and often results in early spontaneous miscarriage. It is exceedingly rare for a triploid fetus to survive to birth. Neonates usually die within hours to days after delivery. After the Dobbs v Jackson Women's Health Organization ruling in July 2022, access to abortion is becoming increasingly limited, and therefore providers should consider the adverse maternal health outcomes that can be associated with triploidy. METHODS: In this case series, we describe three cases of confirmed fetal triploidy that we encountered in our center within 1 year (2021–2022). All three cases were referred to us after House Bill 1259 was passed on July 1, 2020, in Mississippi banning termination of pregnancy based on race, sex, or genetic abnormality. RESULTS: Our first case is a 21-year-old patient referred at 19 weeks 2 days for abnormal second-trimester serum screen. Ultrasound showed an enlarged multicystic placenta and multiple fetal anomalies. Amniocentesis showed a 69,XXY karyotype. Patient was managed expectantly. At 21 week 5 days, patient was diagnosed with superimposed preeclampsia with severe features. Patient underwent medical termination of pregnancy. The second case is a 25-year-old referred at 30 weeks 0 days for concerns of fetal anomalies. Ultrasound confirmed multiple fetal anomalies. Amniocentesis showed a 69,XXY karyotype. Patient was diagnosed with preeclampsia and pulmonary edema and was delivered at 30 weeks 1 day. The neonate passed away at 22 days of life. Our third case is a 20-year-old referred at 24 weeks 0 days for abnormal aneuploidy screening. Ultrasound showed a major cardiac defect and severe fetal growth restriction. Amniocentesis showed a 69,XXY karyotype. Patient was managed expectantly. At 29 weeks 0 days, intrauterine fetal demise was diagnosed. Patient was diagnosed with peripartum depression. CONCLUSION: Women with pregnancies affected by fetal triploidy are at risk of developing preeclampsia. Restricting access to abortion will lead to increased maternal morbidity and mortality rates.

ВЛИЯНИЕ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ НА ТЕЧЕНИЕ БЕРЕМЕННОСТИ И РОДОВ, А ТАКЖЕ ИХ ИСХОДЫ ДЛЯ МАТЕРИ И НОВОРОЖДЕННОГО (СИСТЕМАТИЧЕСКИЙ ОБЗОР)

Significance. COVID-19 is a potentially fatal infection, however data on its progression in pregnant women is currently limited. The most important issues remain the features of the COVID-19 progression in pregnant women, the impact of COVID-19 on the course of pregnancy, approaches to the treatment of pregnant women and their delivery, as well as the impact of a new coronavirus infection on the fetus, the study of which is an urgent task. Purpose: to summarize data on the impact of a new coronavirus infection on pregnancy and delivery, as well as its outcomes for the mother and newborn according to scientific publications by Russian and foreign authors. Material and methods. Relevant publications on COVID-19 progression in pregnant women, the COVID-19 impact on pregnancy, delivery and its outcomes for the mother and newborn were analyzed. The systematic review was conducted according to PRISMA guidelines using PICO(S) criteria. Results. According to data from early research, pregnant women with COVID-19 had a more severe course of the disease, higher risk of gestational complications, higher demand for intensive care in intensive care unit - 1.5% versus 0.9% in non-pregnant women, as well as artificial lung ventilation (1.7 times), although mortality in the groups of pregnant and non-pregnant did not differ equaling to 0.2%. Among possible risks of complications after COVID-19 infection the domestic and foreign literature names spontaneous miscarriages in the first and second trimesters of pregnancy, premature rupture of membranes, premature birth, birth of newborns of low weight for gestational age and prematurity, development of fetoplacental insufficiency, delayed fetal development due to lower utero-placental blood flow during COVID-19, exacerbation of chronic somatic conditions (diseases of the cardiovascular system, respiratory system, autoimmune processes, endocrine disorders), and postpartum bleeding. The COVID-19 effect on fetus is still the subject of numerous discussions and studies, there is evidence that women with COVID-19 have a higher risk of premature birth with all the consequences for the newborn. Conclusion. Physiological changes associated with pregnancy increase maternal susceptibility to infections in general, so the course of the disease may have its own characteristics during pregnancy. The new coronavirus infection is more severe in pregnant women with chronic diseases, obesity, arterial hypertension, and in older age groups. According to the data obtained, adverse outcomes include early and late spontaneous miscarriages, hemostasiological disorders in pregnant women and parturient women, fetoplacental insufficiency with fetal growth retardation, preterm delivery of newborns who are small for gestational age, and their prematurity with all the consequences.

Analysis of factors related to early miscarriage after in vitro fertilization embryo transfer

AimsThis research aims to explore the factors related to early spontaneous miscarriage after in vitro fertilization and embryo transfer (IVF-ET) pregnancy, and to provide guidance for improving pregnancy outcomes. MethodsWe retrospectively analyzed the data for clinical pregnant women (2591 cycles) undergoing IVF-ET at the reproductive center of Peking University People’s Hospital from January 2017 to December 2018; This included 544 ​ET cycles and 2047 frozen embryo transfer cycles. The analysis of factors associated with early miscarriage in the overall population of IVF/intracytoplasmic sperm injection (ICSI) pregnancies (including fresh and thawing cycles) was performed. ResultsThe risk of early miscarriage in the 35–39 age group was 1.35 times higher than that in the <35 age group (OR ​= ​1.35 [1.05,1.73], p ​= ​0.02). In addition, the risk of early miscarriage was 3.88 times higher in the group ≥40 years old than in the group <35 years old (OR ​= ​3.88 [2.68,5.62], p ​< ​0.001). Endometrial thickness also affected the miscarriage rate; the early miscarriage risk with endometrial thickness ≥8.5 ​mm was 0.78 times than that of the <8.5 ​mm group (OR ​= ​0.78 [0.62,0.98], p ​= ​0.03). The early miscarriage rate during frozen embryo transfer was 1.48 times higher than that during fresh embryo transfer (OR ​= ​1.48 [1.08,2.02], p ​= ​0.01), while in the fresh cycle, the risk of early miscarriage with high-quality embryos was 0.5 times lower than that with non-high quality embryos (OR ​= ​0.5 [0.27,0.9], p ​= ​0.02). In the frozen cycle, the risk of early miscarriage in natural cycle transplantation was 0.73 times that in hormone replacement treatment (HRT) cycle transplantation (OR ​= ​0.73 [0.54,0.97], p ​= ​0.03) . ConclusionsAdvanced age is an independent risk factor for early miscarriage, while endometrial thickness at the date of transplantation is an independent protective factor. The risk of early miscarriage in fresh-cycle transplanted embryos is significantly lower than that in frozen embryos, and the number of high-quality embryos in the fresh cycle lowers the miscarriage rate significantly. Natural cycle transplantation has a lower rate of early miscarriage than hormone replacement therapy.

Automated prediction of early spontaneous miscarriage based on the analyzing ultrasonographic gestational sac imaging by the convolutional neural network: a case-control and cohort study

BackgroundIt is challenging to predict the outcome of the pregnancy when fetal heart activity is detected in early pregnancy. However, an accurate prediction is of importance for obstetricians as it helps to provide appropriate consultancy and determine the frequency of ultrasound examinations. The purpose of this study was to investigate the role of the convolutional neural network (CNN) in the prediction of spontaneous miscarriage risk through the analysis of early ultrasound gestational sac images.MethodsA total of 2196 ultrasound images from 1098 women with early singleton pregnancies of gestational age between 6 and 8 weeks were used for training a CNN for the prediction of the miscarriage in the retrospective study. The patients who had positive fetal cardiac activity on their first ultrasound but then experienced a miscarriage were enrolled. The control group was randomly selected in the same database from the fetuses confirmed to be normal during follow-up. Diagnostic performance of the algorithm was validated and tested in two separate test sets of 136 patients with 272 images, respectively. Performance in prediction of the miscarriage was compared between the CNN and the manual measurement of ultrasound characteristics in the prospective study.ResultsThe accuracy of the predictive model was 80.32% and 78.1% in the retrospective and prospective study, respectively. The area under the receiver operating characteristic curve (AUC) for classification was 0.857 (95% confidence interval [CI], 0.793–0.922) in the retrospective study and 0.885 (95%CI, 0.846–0.925) in the prospective study, respectively. Correspondingly, the predictive power of the CNN was higher compared with manual ultrasound characteristics, for which the AUCs of the crown-rump length combined with fetal heart rate was 0.687 (95%CI, 0.587–0.775).ConclusionsThe CNN model showed high accuracy for predicting miscarriage through the analysis of early pregnancy ultrasound images and achieved better performance than that of manual measurement.

Impact of bacterial vaginosis on the reproductive outcomes of IVF: meta-analysis

History: Bacterial vaginosis has been seen to have a negative impact on the reproductive outcomes of in vitro fertilization (IVF). Aim: To determine its impact on the rates of biochemical pregnancy, clinical pregnancy, early spontaneous miscarriage and live newborns. Data source: Bibliographic search according to PRISMA guidelines in the MEDLINE, EMBASE, CINAHL and Cochrane Library databases. Eligibility criteria for the studies: The process for identifying and selecting studies is shown in the PRISMA flowchart. Evidence was evaluated according to the GRADE method. Subjects and interventions: Infertile women with IVF. Diagnosis of bacterial vaginosis according to Nugent or qPCR criteria. Evaluation of studies and summary methods: Forest plot, sensitivity analysis, funnel plots and evaluation of evidence according to GRADE. Results: A total of seven studies were included. We detected an overall statistically significant association with the rate of biochemical pregnancy (OR 0.55; 95%CI: 0.36-0.85; P=0.004) and rate of clinical pregnancy 0.43; 95%CI: 0.22-0.87; P=0.018). This was not the case for early spontaneous miscarriage (OR 1.13; 95%CI: 0.46-2.82; P=0.78) and rate of live newborns (OR 1.63; 95%CI: 0.61- 4.32; P=0.33). Limitations: Observational studies with a small sample and significant heterogeneity between them. Conclusions: Bacterial vaginosis appears to have some impact on the rate of clinical and biochemical pregnancy achieved with IVF.

Restoration Treatment for Female Patients with Non-Bearing Pregnancy at the Early Terms of Gestatione

An important indicator of reproductive health is pregnancy failure, which has no decreasing trend worldwide [1-3]. Despite certain successes achieved in treatment and rehabilitation, the problem of pregnancy failure, especially in early gestation, is still urgent [4-6]. Thus, according to different authors, it ranges from 2 to 55%, reaching up to 80% in the first trimester. Statistically, 15 to 25% of all registered pregnancies are spontaneously miscarried, and 80% of pregnancies are terminated before 12 weeks of gestation. The incidence of spontaneous miscarriage remains consistently high, at 45-88.6% of early spontaneous miscarriages. Direct reproductive losses from non-pregnancy in Ukraine amount to 36-40 thousand unwanted children annually. It has been established that the state of reproductive health depends to a greater extent on the duration of pregnancy failure and the complex of rehabilitation measures [1-3]. When a pregnancy occurs within the first 6 months, after a previous miscarriage, a large number of repeated pregnancy losses have been noted. The rate of pregnancy loss after a single miscarriage is 13-17%, after two miscarriages 36-38%, and with recurrent miscarriage up to 45% [1-3]. After spontaneous abortion it is necessary to rehabilitate a woman's reproductive health regardless of the number of spontaneous miscarriages, taking into account all the causes and conditions that contribute to spontaneous pregnancy termination. The principles of the reproductive health rehabilitation program for women after spontaneous miscarriage include the earliest possible initiation of treatment and rehabilitation measures, the principle of an individual approach to rehabilitation measures for each patient [4-6]. The principle of dynamic control over the effectiveness of rehabilitation and therapeutic measures and the principle of continuity between inpatient, outpatient, and sanatoriumresort units of rehabilitation measures are important when using the methods and means of physical rehabilitation [4-7].

Extracellular Vesicle-Associated MicroRNA-138-5p Regulates Embryo Implantation and Early Pregnancy by Adjusting GPR124.

Functional embryo–maternal interactions occur during the embryo implantation and placentation. Extracellular vesicles with microRNA (miR) between cells have been considered of critical importance for embryo implantation and the programming of human pregnancy. MiR-138-5p functions as the transcriptional regulator of G protein-coupled receptor 124 (GPR124). However, the signaling pathway of miR138-5p- and GPR124-adjusted NLRP3 inflammasome activation remains unclear. In this study, we examine the roles of the miR138-5p and GPR124-regulated inflammasome in embryo implantation and early pregnancy. Human decidual stromal cells were isolated from the abortus tissue and collected by curettage from missed abortion patients and normal pregnant women at 6- to 12-week gestation, after informed consent. Isolated extracellular vesicles from decidua and decidual stromal cells were confirmed by transmission electron microscopy (TEM). Next-Generation Sequencing (NGS) and microarray were performed for miR analysis. The predicated target genes of the differentially expressed miR were analyzed to identify the target genes and their pathway. We demonstrated the down-regulation of miR-138-5p and the overexpression of GPR124 in spontaneous miscarriage compared to normal pregnancy. We also showed the excessive activation of the NLRP3 inflammasome in spontaneous miscarriage compared to normal pregnancy. Here, we newly demonstrate that the miR-138-5p and GPR124-adjusted NLRP3 inflammasome were expressed in extracellular vesicles derived from decidua and decidual stromal cells, indicating that the miR-138-5p, GPR124 and NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome have a potential modulatory role on the decidual programming and placentation of human pregnancy. Our findings represent a new concept regarding the role of extracellular vesicles, miR-138-5p, GPR124, and the NLRP3 inflammasome in normal early pregnancy and spontaneous miscarriage.

OBSTETRICAL PROGNOSIS AFTER UTERINE SEPTUM SECTION BY HYSTEROSCOPYABOUT A CASE REPORT

The septate uterus is the most common congenital uterine malformation resulting from a resorption defect of the inter-mullerian septum. It is frequently associated with conception abnormalities such as early recurrent spontaneous miscarriage (FCS) and late recurrent miscarriage (FCT) but also with fertility abnormalities, without a clear mechanism. The imaging techniques used to diagnose a septate uterus are based on : Endo-vaginal ultrasound, diagnostic hysteroscopy and IRM pelvic . Surgical treatment is based on septum sectioning which is a minimally invasive surgical technique with low risk of complications. This septal section significantly improves the obstetrical prognosis in women with a desire for pregnancy.

A Minority of Women of Child Bearing Potential Are Tested for Pregnancy before Chemoimmunotherapy: An Australian Cancer Centre Experience

Background: Chemotherapy is potentially harmful to the developing foetus and there is limited data on the foetal impact of immunotherapy except for rituximab. Therefore determining pregnancy status prior to initiation of chemo- and or immuno-therapy (CIT) should be standard of care. Repeat screening or testing during and after chemotherapy should be considered as women often cannot tell that they are pregnant due to overlapping symptoms of pregnancy, malignancy and treatment. This is of particular importance in women who are not on effective forms of contraception for personal choice or clinical reasons. Clinicians cannot presume that a patient's pregnancy status has been checked, or rely on any assumptions of abstinence, contraception or infertility based on secondary amenorrhoea. While CIT teratogenicity should be part of the informed consent discussion and it is recommended that pregnancy screening occur prior to CIT, there are no specific guidelines on this or on testing during CIT. It is our institutional standard to document consent using a standard tick box form to confirm a discussion of common and uncommon side effects of treatment, long term and life threating complications and impacts on fertility. Teratogenicity, pregnancy implications or contraception are not specified. We performed a retrospective review to evaluate the uptake of pregnancy screening prior to and during first-line CIT as well as an audit of documentation of contraception counselling in haematological and solid-organ malignancies at a large Australian tertiary cancer centre.Methods: We searched our electronic outpatient medical record database for Women of Child Bearing Potential (WoCBP) who were diagnosed with a malignancy and received outpatient based CIT between May 1 2015 and June 12 2020. WoCBP was defined as women 18-55 years of age with no record of menopause or definitive infertility. We captured patient demographics, disease details and CIT regimen. We collected result of any serum or urine b-HCG pregnancy tests done within 90 days prior to or during CIT administration and if positive, the pregnancy outcome. We captured any documentation regarding contraception prior to or during treatment.Results: A total of 415 WoCBP with a median age of 42 years (range 19-51) were included. The majority of women (79.3%) were treated for solid organ malignancies compared to haematological malignancies (20.7%) (Table 1). Only 17.1% were screened for pregnancy prior to its initiation. The average time between screening and CIT initiation was 19.5 days (range 0-90 days). Given the broad range of regimens and taking into consideration teratogenicity potential, CIT was categorised as immunotherapy alone (32.5%), chemotherapy containing an alkylating agent (25.8%) or an antimetabolite (3.9%), combination chemoimmunotherapy (15.2%) and other (22.7%). Rates of pregnancy screening within these categories is represented in Figure 1.One patient with early breast cancer had a positive pregnancy test during her 4 th cycle of adjuvant chemotherapy with paclitaxel, in the emergency department for a presentation of nausea, anorexia, abdominal pain and diarrhoea. The outcome in this case was an early spontaneous miscarriage estimated at 3-4 weeks gestation. This is the only patient who had a pregnancy test beyond the first cycle of CIT. Only 14.8% of patients had documentation of past or present contraception methods. None of the patients had documentation regarding counselling on recommended forms of contraception.Conclusion: A minority of WoCBP received a pregnancy test prior to commencing CIT for haematological or solid organ malignancy, and none intentionally received a test prior to subsequent chemotherapy cycles through the oncology/haematology service. Also none of the women had documented counselling on contraception. These results are concerning because missing a positive pregnancy test puts women at risk of foetal complications, accidental miscarriage, potential bleeding risks and avoidable psychosocial stress. Our results are consistent with the 2 other reports on this topic and are likely generalizable to other cancer centres. This highlights the urgent need for guidelines to increase the rate of pregnancy testing in WoCBP receiving CIT and contraception counselling prior to CIT. [Display omitted] DisclosuresHamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Changes in the cytokine status in women with chronic liver pathology during reproductive losses in the first trimester

Research objective: to determine the level of serum cytokines in the pregravidar period in women with chronic diseases of the hepatobiliary system and reproductive losses in the first trimester in the anamnesis.Materials and methods. 90 patients of reproductive age with chronic pathology of the hepatobiliary system (liver steatosis and non-alcoholic steatohepatitis) were examined. All patients had spontaneous miscarriages in the early stages of gestation in anamnesis. The research was conducted during the pregravid preparation period. The laboratory research included an additional study of the interleukins (ІL-2, ІL-6, ІL-8, ІL-10) and tumor necrosis factor (TNFα) in the blood serum using enzyme immunoferment assay. 8 female donors were examined to determine the reference norm of cytokines in the blood serum. Results. The cytokine status in patients with chronic pathology of the hepatobiliary system against the background of early miscarriage was characterized by an increase in proinflammatory cytokines (TNFα in 2,29 times more, ІL-2 in 1,46 times, ІL-6 in 1,84 times and ІL-8 in 1,50 times) and anti-inflammatory cytokines (ІL-10 in 1,31 times). The integral indices that are characterizing the oppositional cytokines ratio increased (TNFα/ІL-10, ІL-2/ІL-10 and ІL-6/ІL-10) which indicates an inflammatory process in the body. Minimal changes were registered in patients with signs of steatosis – a moderate increase in proinflammatory cytokines (TNFα is 1,34 times more, ІL-2 in 1,18 times, ІL-6 in 1,33 times and ІL-8 in 1,13 times) and preservation within the reference norm of ІL-10. The maximum imbalance of serum cytokines was observed in the exacerbation of non-alcoholic steatohepatitis – a significant increase in proinflammatory cytokines (TNFα is 3,66 times more, ІL-2 in 1,95 times, ІL-6 in 2,57 times and ІL-8 in 2,18 times) against the background of a moderate increase in ІL-10 (1,30 times). In patients with clinical and laboratory signs of remission of non-alcoholic steatohepatitis a moderate increase in proinflammatory (TNFα is 1,87 times more, ІL-2 in 1,20 times, ІL-6 in 1,61 times and ІL-8 in 1,20 times) and anti-inflammatory (ІL-10 in 1,51 times) cytokines was diagnosed. The analysis of the integral indices of oppositional cytokines showed a tendency to increase their values in patients with liver steatosis and non-alcoholic steatohepatitis in the phase of clinical and laboratory remission. During the period of the non-alcoholic steatohepatitis exacerbation a considerable increase in the studied coefficients was revealed. Conclusions. Changes in the cytokine status are noted in patients with early spontaneous miscarriages in anamnesis and chronic diseases of the hepatobiliary system, which are characterized by the severity of inflammatory reactions and progression of the pathological process in liver. Obtained results can be used to predict miscarriage and be taken into account in the program of drug preparation in the pregravid period.

New aspects in the pathogenesis of miscarriage in women with extragenital pathology

Study objective: to determine the dynamics of type 9 metalloproteinase (MMP-9) and its tissue inhibitor-1 (TIMP-1) in the pathogenesis of early miscarriage in women with chronic diseases of the hepatobiliary system.Materials and methods. The study included 39 women with a history of early pregnancy miscarriage, who were diagnosed with chronic liver diseases as a result of clinical, instrumental and laboratory studies (17 persons with steatosis and 22 persons with non-alcoholic steatohepatitis). The control group consisted of 8 women without somatic pathology and 8 pregnant women at the first trimester of gestation. MMP-9 and TIMP-1 value in the blood serum was determined by the enzyme immunoassay.Results. MMP-9 and TIMP-1 growth in the blood serum of women with a history of miscarriage was established in the pre-gravidar period. The most significant increase in the parameters of the intercellular matrix was found in patients with non-alcoholic steatohepatitis. MMP-9 and TIMP-1 increased in in blood serum in the first trimester in women with liver diseases. MMP-9 increased against the background of a decrease in the TIMP-1 activity in patients with the threat of premature pregnancy termination. Miscarriage was diagnosed in patients with a minimum value of a tissue inhibitor. Conclusions. There is an imbalance between MMP-9 and TIMP-1 in the blood serum in women with early miscarriage and chronic diseases of the hepatobiliary system. MMP-9 and TIMP-1 level in patients with hepatic steatosis is lower than in patients with non-alcoholic steatohepatitis. MMP-9 increased during physiological pregnancy, and the TIMP-1 activity practically did not change, which indicates the role of MMP-9 in the initial stages of placentation. MMP-9 value in women with a burdened premorbid background with a physiological course of pregnancy and threatening early spontaneous miscarriage was significantly different. The highest activity of MMP-9 was in women with the threat of spontaneous miscarriage in the early stages. TIMP-1 in the first trimester in women with chronic liver disease increased in those with a favorable course of pregnancy and decreased in the threat of spontaneous miscarriage. Such changes in MMP-9 and TIMP-1 in patients with miscarriage indicate the accumulation of intercellular matrix and sclerotic changes in the vessels that provide blood to the uterus.

Multidisciplinary management of anti‐PP1Pk or anti‐P alloimmunization during pregnancy: A new case with anti‐P and a literature review

AbstractBackgroundRed blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti‐PP1Pk or anti‐P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti‐P and a history of recurrent miscarriages.Case ReportThis P2k (GLOB:‐1; P1PK:‐1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non‐reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti‐P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti‐P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required.Discussion and Review of the LiteratureThe P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:‐1; P1PK:1,3), P2k (GLOB:‐1; P1PK:‐1,3), or Tj(a‐)/p (GLOB:‐1; P1PK:‐1,‐3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported.ConclusionImmunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti‐PP1Pk or anti‐P fetomaternal incompatibilities.

Спектр, иммунохимические свойства и диагностическое значение антифосфолипидных антител у женщин с ранним привычным выкидышем

Спектр, иммунохимические свойства и диагностическое значение антифосфолипидных антител у женщин с ранним привычным выкидышем

Genetic testing on products of conception and its relationship with body mass index.

The study aimed to investigate the relationship between elevated maternal body mass index (BMI) and foetal chromosomal aberrations by performing single-nucleotide polymorphism (SNP) array-based genetic testing on products of conception (POC). We retrospectively reviewed the data for 1068 assisted reproductive technology (ART)-conceived POC originated from 1068 patients with early spontaneous miscarriage. First, all types of chromosomal abnormalities were defined. Then, the baseline characteristics, including maternal age, BMI, thyroid-stimulating hormone (TSH), gestational age, fertilization method, reasons for fertility treatment, embryo transfer (ET) cycle, stage of embryo development and the embryo morphology grade, were compared between chromosomally normal and abnormal POC groups. Finally, a multivariate logistic regression model was used to analyse various factors affecting the foetal chromosomal abnormality rate. The SNP array results showed that 45.3% (484/1068) of POC were chromosomally normal and that 54.7% (584/1068) of POC presented chromosomal abnormalities. Of these 584 chromosomally abnormal POC, 388 (66.4%) were trisomy, 42 (7.2%) had a monosomy, 68 (11.6%) were found with segmental aneuploidy, 46 (7.9%) were mosaic, 28 (4.8%) were identified as polyploidy and 12 (2.1%) were euploid samples with uniparental disomy (UPD). Multivariate logistic regression results showed that the risk of miscarrying chromosomally abnormal POC increased 1.424-fold in women with normal BMI compared to women with an elevated BMI (≥ 25kg/m2) (OR = 1.424, 95% CI = 1.074-1.888, p = 0.014). Women with an elevated BMI (≥ 25kg/m2) are more likely to miscarry chromosomally normal POC.