Pregnancy Failure Research Articles

Multi-omics PGT: re-evaluation of euploid blastocysts for implantation potential based on RNA sequencing.

In addition to chromosomal euploidy, can the transcriptome of blastocysts be used as a novel predictor of embryo implantation potential? This retrospective analysis showed that based on differentially expressed genes (DEGs) between euploid blastocysts which resulted and did not result in a clinical pregnancy, machine learning models could help improve implantation rates by blastocyst optimization. Embryo implantation is a multifaceted process, with implantation loss and pregnancy failure related not only to blastocyst euploidy but also to the intricate dialog between blastocyst and endometrium. Although in vitro studies have revealed the characteristics of trophectoderm (TE) differentiation in implanted blastocysts and the function of TE placentation at the implantation site, the precise molecular mechanisms of embryo implantation and their clinical application remain to be fully elucidated. This study involved 102 patients who underwent 111 cycles for preimplantation genetic testing for aneuploidies (PGT-A) between March 2022 and July 2023. The study included 412 blastocysts biopsied at Day 5 [D5] or Day 6 [D6] for patients who underwent PGT-A. The biopsy lysates were split and subjected to DNA and RNA sequencing (DNA- and RNA-seq). One part was used for PGT-A to detect DNA copy number variations, whereas the other part was assessed simultaneously by RNA-seq to determine the transcriptome characteristics. To validate the reliability and accuracy of RNA-seq obtained from this strategy, we initially analyzed the transcriptome of blastocysts with chromosomal aneuploidies. Subsequently, we compared the transcriptomic features of blastocysts with different rates of formation (D5 vs D6) and investigated the network of interactions between key blastulation genes and the receptive endometrium. Then to evaluate the implantation potential of euploid blastocysts, we identified DEGs between euploid blastocysts that resulted in clinical pregnancy (defined as the presence of a gestational sac detected by ultrasound after 5 weeks) and those that did not. These DEGs were then employed to construct a predictive model for optimizing blastocyst selection. The successful detection rate of PGT-A was remarkably high at 99.8%. The RNA data may infer aneuploidy for both trisomy and monosomy. Between the euploid blastocysts that formed on D5 and D6, 187 DEGs were predominantly involved in cell differentiation for embryonic placenta development, the PPAR signaling pathway, and the Notch signaling pathway. These D5/D6 DEGs also exhibited a functional dialog with the receptive phase endometrium-specific genes through protein-protein interaction networks, indicating that the embryo undergoes further differentiation for post-implantation development. Furthermore, a modeling strategy using 280 DEGs between blastocysts leading to successful clinical pregnancies or failing to produce clinical pregnancies was implemented to refine the euploid embryo optimization, achieving areas under the curves of 0.88, 0.71, and 0.84 for the random forest (RF), support vector machine, and linear discriminant analysis models, respectively. Finally, a retrospective analysis of 83 transferred euploid blastocysts using the RF model identified three types of euploid embryos with a decreasing trend in implantation potential. Notably, the implantation rate of the good group was significantly higher than that of the moderate group (88.6% vs 50.0% P = 0.001) and that of the moderate group was higher than that of the poor group (50.0% vs 20.8%, P = 0.035). The sample size was insufficient; thus, a prospective study is needed to verify the clinical effectiveness of the above model. Because we did not analyze blastocysts that led only to biochemical pregnancies but failed clinical pregnancies separately, our classification system still must be modified to screen these embryos. Transcriptomic analysis of blastocysts offers a novel approach for predicting embryo implantation potential, which can be utilized to optimize clinical embryo selection. The ranking system may be effective in reducing the times and costs involved in achieving a clinical pregnancy. This study was funded by the "Pioneer" and "Leading Goose" R&D Program of Zhejiang (No. 2023C03034), the National Natural Science Foundation of China (82101709), and the National Key Research and Development Program for Young Scientists of China (No. 2022YFC2702300). The authors state no competing interests. N/A.

SMOTE-Based Automated PCOS Prediction Using Lightweight Deep Learning Models.

The reproductive age of women is particularly vulnerable to the effects of polycystic ovarian syndrome (PCOS). High levels of testosterone and other male hormones are frequent contributors to PCOS. It is believed that miscarriages and ovulation problems are majorly caused by PCOS. A recent study found that 31.3% of Asian women have been afflicted with PCOS. Healing women with life-threatening disorders associated with PCOS requires more research. In prior research, methods have involved autonomously classified PCOS using a number of different machine learning techniques. ML-based approaches involve hand-crafted feature extraction and suffer from low performance issues, which cannot be ignored for the accurate prediction and identification of PCOS. Hence, predicting PCOS using cutting-edge deep learning methods for automated feature engineering with better performance is the prime focus of this study. The proposed method suggests three lightweight (LSTM-based, CNN-based, and CNN-LSTM-based) deep learning models, incorporating SMOTE for dataset balancing to obtain a valid performance. The proposed three models tend to offer an accuracy of 92.04%, 96.59%, and 94.31%, an ROC-AUC of 92.0%, 96.6%, and 94.3%, the number of parameters of 6689, 297, and 13285, and a training time of 67.27 s, 10.02 s, and 18.51 s, respectively. In addition, the DeLong test is also performed to compare AUCs to assess the statistical significance of all three models. Among all three models, the SMOTE + CNN models performs better in terms of accuracy, precision, recall, AUC, number of parameters, training time, DeLong's p-value over the other. Moreover, a performance comparison is also carried out with other state-of-the-art PCOS detection studies and methods, which validates the better performance of the proposed model. Thus, the proposed model provides the greatest performance, which can lead to a reduction in the number of failed pregnancies and help in finding PCOS in the early stages.

Heart Activity Visualization in Embryos with Crown-Rump Length Shorter Than 5 mm and Its Role in Prediction of Early Pregnancy Failure in Patients of Recurrent Early Pregnancy Loss

Heart Activity Visualization in Embryos with Crown-Rump Length Shorter Than 5 mm and Its Role in Prediction of Early Pregnancy Failure in Patients of Recurrent Early Pregnancy Loss

PSIII-2 Exploring differential gene expression and pathways associated with pregnancy outcomes in beef heifers

Abstract Heifer fertility is a key factor in the success of beef production systems, as the reproductive performance of a heifer correlates with her stayability in the breeding herd. However, despite being reproductively mature and physically healthy, 5 to 15% of these heifers fail to conceive within a designated breeding season. The underlying physiological mechanisms preventing these heifers from achieving pregnancy remain elusive. Therefore, this study aimed to determine differentially expressed genes (DEGs) and biological pathways associated with pregnancy outcomes in beef heifers. Angus-Simmental crossbred heifers were subjected to an estrus synchronization and fixed-time artificial insemination (AI) program (7-d CO-Synch + CIDR) and blood samples were collected at the time of AI for isolation of peripheral white blood cells (PWBC). After pregnancy check, heifers were classified as pregnant (P) and non-pregnant (NP). Based on that, 6 animals per group were randomly selected for total RNA isolation from the PWBC samples, and genome-wide expression was measured through RNA sequencing. The RNA-Seq data were analyzed using an in-house bioinformatics pipeline, with filtered reads aligned to the Bos taurus reference genome using STAR. DEGs were identified using DESeq2, followed by functional analysis using ShinyGO. Our approach unveiled 230 DEGs, comprising 102 up and 128 downregulated genes in the NP group (P-value ≤ 0.05 and |log2FC| > 0.5). Upregulated genes included those from the cytochrome P450 superfamily (CYP27B1 and CYP2U1). The genes SCML2, USIG2, and FBP1 were upregulated and have been associated with immune response and increased PWBC counts. This may be related to the over-representation of biological processes involved in cell division based on the upregulated genes. KEGG pathway over-representation analysis of DEGs retrieved allograft rejection, graft-versus-host disease, type I Diabetes Mellitus, insulin signaling pathway, and transcriptional misregulation of cancer. These pathways included genes such as BOLA-DQB, PRKAR1B, CALML4 and JUP, which were reported as downregulated during times of inflammatory response. Another downregulated gene was GZMB, which is needed for proper cell targeting during immune response. This finding may provide a link between immune function and early pregnancy failure. However, the relationship between the immune system and pregnancy warrants further investigation. Our results shed light on the molecular mechanisms underlying reproductive performance in beef heifers and support previous studies associating immune function with pregnancy outcomes. These differentially expressed genes may be further explored as potential avenues for enhancing fertility in beef production systems.

391 The impact of trace mineral source on systemic immunological status associated with early embryonic loss in lactating dairy cattle

Abstract Milk production has doubled from 1970 to 2009 but has been associated with a decline in fertility. Around 25% of failed pregnancies in dairy cattle are due to embryonic loss. Mineral bioavailability may affect embryonic retention, so we hypothesized that Zn, Cu, and Mn sources will influence systemic immunological status, which affects early embryonic retention. Holstein cows (n = 58) were randomly assigned to one of two daily oral drench trace mineral (Zn, Cu, and Mn) treatments 30 d before breeding (d -30): 1) Inorganic (ITM) or 2) Metal Methionine Hydroxy Analog Chelate (MMHAC). Before treatments began, cows were assigned to a semen type, beef vs. Holstein, equally, across treatments. All cows underwent a double Ovsynch protocol and were artificially inseminated on d 0. Humoral immunological status was assessed in serum samples taken on d 0 and d 7. Immune activity was quantified via a D2Dx systemic immunity score, which assesses samples for the presence of IgG, IgM, cytokines, and complement proteins. Ultrasonography was utilized for pregnancy confirmation on d 35, classifying cows as pregnant (P) or open. Progesterone analysis from d 21 plasma was used to categorize open cows as either non-pregnant (NP) or early embryonic loss (EEL). Statistical analyses in R Studio were completed, in two models based on pregnancy (P vs EEL and NP vs EEL), to determine the effects of mineral treatment, pregnancy status, semen type, and all interactions on humoral immune status. In the P vs EEL model, there were no effects (P > 0.30) of semen type, mineral treatment, pregnancy status, or any interactions on systemic immunity score on the day of breeding (d 0) or d 7. On d 0, cows provided MMHAC had a systemic immunity score of 0.073 ± 0.008 but were not different (P > 0.34) from ITM cows (0.063 ± 0.006). This trend continued on d 7 with systemic immunity scores of MMHAC cows not differing (P > 0.32) from ITM cows (0.055 ± 0.004 and 0.061 ± 0.003; respectively). There was a tendency (P = 0.10) for the three-way interaction of semen type x pregnancy x treatment to influence the immunity score change from d 0 to d 7. Pregnant cows on ITM treatment bred with beef semen had a positive change in immunity score (0.020 ± 0.0085). Whereas ITM cows bred with Holstein semen that underwent EEL had a negative change (-0.015 ± 0.0085); all other means were intermediate. In the NP vs EEL model, there were no effects (P > 0.14) of semen type, treatment, pregnancy status, or any interactions on systemic immunity score on d 0, d 7, or the change between d 0 and d 7. In summary, trace mineral bioavailability tended to affect systemic immunological status in P vs EEL cows but not in NP vs EEL cows, which may allow for the elucidation of immunological status differences during pregnancy establishment.

Evaluating the effectiveness and adverse effects of oral versus transdermal estradiol for endometrial preparation in frozen-thawed embryo transfer: a randomized controlled trial

BackgroundEndometrial preparation significantly influences the success of embryo transfer procedures. Although both oral and transdermal estradiol are common methods for endometrial priming, their efficacy and potential side effects remain uncertain. This randomized controlled trial aims to compare the effectiveness of oral and transdermal estradiol in endometrial preparation, while also evaluating their respective side effects in patients undergoing assisted reproduction treatments.MethodThis randomized clinical trial (ISRCTN15301227) was conducted at Hung Vuong Hospital between July 2020 and March 2022. Among 550 eligible patients undergoing frozen embryo transfer cycles, we included 380 patients for the study. The study protocol and all materials received approval from the Ethics Committee of Hung Vuong Hospital (1315/CN-HĐĐĐ). Participants were randomly assigned to one of two groups: Group A (n =190) received oral estradiol at an initial dose of 4 mg per day for 7 days, with the dose increased according to clinical response. Group B (n =190) received transdermal estradiol at an initial dose of 2 measures of 2.5 g estradiol gel per day for 7 days, with the dose similarly increased according to clinical response. Treatment in both groups began on days 2–3 of the menstrual cycle, with the maximum duration of estradiol administration being 27 days. We compared estradiol levels on the day of progesterone administration, duration of treatment, total estradiol dose, endometrial thickness, pregnancy outcomes, and any observed side effects between the two groups.ResultsGroup A exhibited significantly higher estradiol levels on the day of progesterone administration compared to Group B (270.5 pg/ml versus 186.5 pg/ml, p < 0.001). However, the comparison revealed no significant difference in endometrial thickness between the two groups (10.5 mm versus 10.6 mm, p = 0.85). Furthermore, pregnancy rates including positive human chorionic gonadotropin, clinical pregnancy, ongoing pregnancy, live birth, and pregnancy failure were also found to be similar between the two groups. Notably, a greater proportion of patients in Group A experienced mild side effects compared to those in Group B (20.3% versus 10.1%, respectively; n =37 versus n =18), and this discrepancy was found to be statistically significant (p = 0.007).ConclusionTransdermal estradiol offers comparable endometrial thickness and pregnancy outcomes, along with improved patient compliance and fewer side effects compared to oral estradiol.

Role of Hysteroscopy in the Management of Uterine Vascular Malformations with a Focus on Enhanced Myometrial Vascularity – A Review of Diagnosis and Treatment with the Suggested Algorithm

Abstract Postpregnancy bleeding is common after failed pregnancy, termination of pregnancy, and postnatally after both vaginal and cesarean delivery. Pelvic ultrasound (US) is usually the initial imaging modality of choice to ascertain the cause when the bleeding is heavy or prolonged. When used in combination with Doppler studies, US can help differentiate retained products of conception (RPOC) from rarer uterine vascular malformations (UVM), including true arterial vascular malformations and areas of enhanced endometrial vascularity (EMV), which may themselves be associated with any RPOC present. While the management of RPOC is well established and has evolved from an almost universal surgical approach to increasingly more medical or expectant alternatives, clinical decisions over the management of a concurrent UVM are less clear and treatment options need to be individualized depending on features of the lesion and the clinical situation with hysteroscopy featured as an important modality, especially when dealing with EMV’s. In this review, we discuss the role of hysteroscopy in the treatment of enhanced myometrial vascularity with and without associated RPOC and propose a management algorithm.

Peripartum heart failure in Finland: A population-based record linkage study.

Heart failure in late pregnancy and the postpartum period (HFPP) is a rare but potentially life-threatening condition, with peripartum cardiomyopathy (PPCM) being the most common subtype. This study aims to comprehensively investigate the prevalence of HFPP in the Finnish population and identify the underlying risk factors associated with its occurrence. We conducted a retrospective analysis using data from the Finnish Medical Birth Register and the Finnish Care Register for Health Care, covering 1996 to 2021. The dataset comprised 1387457 deliveries. HFPP cases were identified based on specific ICD-10 codes. To ensure the accuracy of our findings, we excluded cases with pre-existing cardiomyopathies and other significant cardiac diseases diagnosed before pregnancy. We employed logistic regression models to evaluate the associations between maternal factors and the incidence of HFPP. We identified 159 cases of HFPP, resulting in an incidence rate of 11.5 per 100000 deliveries. This incidence is comparable with rates reported in other Scandinavian countries and lower than those observed in Germany. Consistent with findings from European cohorts, our study confirmed that pregnancy-associated hypertensive disorders, particularly preeclampsia, as well as complications such as preterm delivery, twin pregnancy and elective caesarean section, are substantial risk factors for HFPP. These results support previous research linking angiogenic imbalance to the pathogenesis of PPCM. Significant risk factors for HFPP included maternal pre-pregnancy body mass index ≥35 [adjusted odds ratio (aOR) 2.04, 95% confidence interval (CI) 1.28-3.25, P=0.003], history of maternal hypertensive disorder (aOR 2.44, 95% CI 1.22-4.88, P=0.012), gestational hypertension without significant proteinuria (aOR 2.14, 95% CI 1.27-3.61, P=0.004), preeclampsia (aOR 2.43, 95% CI 1.39-4.23, P=0.002), type 1 or type 2 diabetes (aOR 3.27, 95% CI 1.66-6.45, P<0.001) and twin pregnancy (aOR 2.74, 95% CI 1.37-5.49, P=0.005). Additionally, extensive prepartum [odds ratio (OR) 2.86, 95% CI 1.18-6.98, P=0.018] and postpartum blood loss (OR 2.50, 95% CI 1.44-5.02, P=0.001) and maternal mental disorders (OR 7.39, 95% CI 4.10-13.31, P<0.001) were significantly more common among HFPP patients. The incidence of HFPP among women in Finland from 1996 to 2021 was low. HFPP exhibited a strong association with several risk factors, including preeclampsia, obesity, preterm delivery, twin pregnancy, elective caesarean section, multifoetal births, type 1 and type 2 diabetes, significant prepartum and postpartum blood loss and maternal mental health disorders. These findings underscore the importance of targeted interventions and careful monitoring in high-risk groups to mitigate the impact of HFPP on maternal health.

Response of bovine endometrium to interferon tau in the presence of lipopolysaccharide

We recently demonstrated that conceptus-derived interferon tau (IFNT), responsible for maternal recognition in cattle, acts on the uterus in a dose- and time-dependent manner by upregulating key interferon-stimulated genes (ISGs) in the endometrium. In high producing dairy cows, postpartum uterine infection is a major factor influencing fertility and pregnancy outcome. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria such as Escherichia coli, generates an altered uterine environment by inducing excessive inflammation at the maternal-conceptus interface. Thus, we aimed to investigate whether the endometrial response to IFNT is altered in the presence of LPS. Endometrial explants were isolated from uteri collected at a local abattoir from Holstein Friesian cows (n = 8) during the mid-luteal stage of the estrous cycle, and cultured in RPMI medium for 24 h in 5 % CO2 in humidified air without (control), or with IFNT (100 ng/mL), a single Day 15 conceptus, LPS (1 μg/mL), both IFNT and LPS, or both a Day 15 conceptus and LPS. Incubation with IFNT and a Day 15 conceptus up-regulated (P < 0.05) well-known classical ISGs (ISG15, OAS1, MX1 and MX2) as well as other candidate ISGs (CMPK2, IFI35, TRIM38 and TNFSF10) and down-regulated expression of IL1B in endometrial explants. Incubation with LPS increased (P < 0.05) abundance of NFKB1 (a key transcription factor involved in inflammatory and immune response), TNFA, IL1B and IL6 (pro-inflammatory cytokines), IL10 (anti-inflammatory cytokine), IL8, CXCL1, CXCL3 and CCL2 (chemokines), and, to a lesser extent, classical ISGs in endometrial explants. However, LPS did not alter endometrial response to IFNT, irrespective of IFNT concentration (1, 10 or 100 ng/mL). Results suggest that the expression of ISGs, up-regulated by conceptus-derived IFNT, is not altered in the endometrium in the presence of LPS; however, the increased expression of inflammation-related genes induced by LPS indicate an altered endometrial immune response that may be associated with compromised pregnancy establishment or pregnancy failure.

Exogenous melatonin ameliorates embryo-maternal cross-talk in early pregnancy in sheep.

Melatonin plays a crucial role in enhancing reproductive performance in small ruminants. This paper reveals the effects of exogenous melatonin on the placental and endometrial rearrangement in early pregnancy in sheep. Early pregnancy losses cause 25% of pregnancy failures in small ruminants because of asynchrony between conceptus and uterine signals. In this context, melatonin plays a crucial role in sheep reproductive dynamics, but little is known about its effects during the peri-implantation period. We hypothesized that melatonin supports embryo implantation by modulating the uterine microenvironment. This study aimed to assess the effects of exogenous melatonin on the endometrial and early placental rearrangement. Ten multiparous ewes either did (MEL, n = 5) or did not (CTR, n = 5) receive a subcutaneous melatonin implant (18 mg) 50 days before a synchronized mating. On day 21 of pregnancy, the sheep were euthanized. MEL ewes exhibited a higher prolificity rate (2.8 vs 2.0 embryos/ewe) and plasma progesterone levels (3.84 vs 2.96 ng/mL, P < 0.05) than did CTR ewes. Groups did not differ significantly in embryo crown-rump length. MEL placentas had significantly (P < 0.001) more binucleated trophoblast cells in the chorion region, and ovine placental lactogen expression was significantly (P < 0.05) more strongly upregulated than in CTR. Exogenous melatonin increased significantly (P < 0.05) gene expression of angiogenic factors (VEGFA, VEGFR1, IGF1R), IFNAR2, and PR in the caruncular endometrium. Expression of the MT2 receptor in the endometrium and placenta was significantly (P < 0.05) higher in the MEL group. These results indicate that melatonin implants acted differentially on uterine and placental rearrangement. Melatonin increases differentiation in the placenta and induces changes that could promote vessel maturation in the endometrium, suggesting that it enhances the uterine microenvironment in the early stage of pregnancy in sheep.

Obstetric anesthesia management of dilated cardiomyopathies and heart failure: a narrative review

Pregnancy in patients with dilated cardiomyopathy carries a significantly increased risk of maternal mortality or severe morbidity, and pregnancy is typically considered contraindicated for patients with severely reduced ventricular function. Nonetheless, anesthesiologists will still encounter patients with cardiomyopathy requiring delivery or termination care. This review describes how NT-ProBNP testing and echocardiography can help with early recognition of heart failure in pregnancy, and describes a suggested approach to anesthetic management of patients with cardiomyopathies or acute heart failure, including hemodynamic goals, use of vasoactive medications and mechanical support. Vaginal delivery, with effective neuraxial anesthesia is the preferred mode of delivery in most patients with cardiomyopathy, with cesarean delivery reserved for maternal or fetal indications. The Pregnancy Heart Team is vital in coordinating the multidisciplinary care necessary to safely support these patients through pregnancy.

Risk Factors of Pregnancy Failure in Infertile Patients Undergoing Assisted Reproductive Technology

Background: Assisted Reproductive Technology (ART) represents a critical advancement in the treatment of infertility, providing hope to many couples struggling to conceive naturally. Despite its success, pregnancy failure remains a significant concern, influenced by various factors such as age, BMI, and underlying medical conditions. Objective: The main objective of this study was to identify the risk factors associated with pregnancy failure in infertile patients undergoing ART treatments. Methods: This clinical audit was conducted at Bahria International Hospital, Rawalpindi, from January 2023 to January 2024. Data were collected from 85 patients undergoing ART treatments, including In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). The study included comprehensive demographic information, clinical history, ART cycle details, laboratory results, and lifestyle factors. Pregnancy failure was defined as either biochemical pregnancy loss or clinical pregnancy loss. Ethical approval was obtained, and data were analyzed using SPSS version 25. Descriptive statistics summarized patient characteristics, while comparative analysis and multivariate logistic regression were used to identify significant risk factors. Results: The study included 85 patients with a mean age of 34.5 years. Those experiencing pregnancy failure had a higher mean age of 36.2 years compared to 33.2 years in those without pregnancy failure. The mean BMI was higher in the pregnancy failure group (26.0 kg/m²) versus the no pregnancy failure group (23.8 kg/m²). Significant risk factors for pregnancy failure included older age (OR=1.15, 95% CI 1.05-1.25, p=0.002), higher BMI (&gt;25 kg/m²) (OR=2.45, 95% CI 1.10-5.47, p=0.03), and the presence of underlying medical conditions (OR=1.90, 95% CI 1.02-3.55, p=0.04). Conclusion: Older age, higher BMI, and underlying medical conditions significantly increased the risk of pregnancy failure in infertile patients undergoing ART. Personalized treatment approaches addressing these risk factors could improve ART outcomes and enhance the chances of successful pregnancies.

Monoamine oxidases activity maintains endometrial monoamine homeostasis and participates in embryo implantation and development

BackgroundMonoamine oxidases (MAOs) is an enzyme that catalyzes the deamination of monoamines. The current research on this enzyme is focused on its role in neuropsychiatric, neurodevelopmental, and neurodegenerative diseases. Indeed, MAOs with two isoforms, namely, A and B, are located on the outer mitochondrial membrane and are widely distributed in the central nervous system and peripheral tissues. Several reports have described periodic changes in the levels of this enzyme in the human endometrial tissue.ResultsThe novel role of MAOs in endometrial receptivity establishment and embryonic development by maintaining monoamine homeostasis was investigated in this study. MAOs activity was observed to be enhanced during the first trimester in both humans and mice under normal conditions. However, under pathological conditions, MAOs activity was reduced and was linked to early pregnancy failure. During the secretory phase, the endometrial stromal cells differentiated into decidual cells with a stronger metabolism of monoamines by MAOs. Excessive monoamine levels cause monoamine imbalance in decidual cells, which results in the activation of the AKT signal, decreased FOXO1 expression, and decidual dysfunction.ConclusionsThe findings suggest that endometrial receptivity depends on the maintenance of monoamine homeostasis via MAOs activity and that this enzyme participates in embryo implantation and development.

The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.

Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. Invitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

A Lexicon for First-Trimester US: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

The Society of Radiologists in Ultrasound convened a multisociety panel to develop a first-trimester US lexicon based on scientific evidence, societal guidelines, and expert consensus that would be appropriate for imagers, clinicians, and patients. Through a modified Delphi process with consensus of at least 80%, agreement was reached for preferred terms, synonyms, and terms to avoid. An intrauterine pregnancy (IUP) is defined as a pregnancy implanted in a normal location within the uterus. In contrast, an ectopic pregnancy (EP) is any pregnancy implanted in an abnormal location, whether extrauterine or intrauterine, thus categorizing cesarean scar implantations as EPs. The term pregnancy of unknown location is used in the setting of a pregnant patient without evidence of a definite or probable IUP or EP at transvaginal US. Since cardiac development is a gradual process and cardiac chambers are not fully formed in the first trimester, the term cardiac activity is recommended in lieu of 'heart motion' or 'heartbeat.' The terms 'living' and 'viable' should also be avoided in the first trimester. 'Pregnancy failure' is replaced by early pregnancy loss (EPL). When paired with various modifiers, EPL is used to describe a pregnancy in the first trimester that may or will not progress, is in the process of expulsion, or has either incompletely or completely passed. © RSNA and Elsevier, 2024 Supplemental material is available for this article. This article is a simultaneous joint publication in Radiology and American Journal of Obstetrics & Gynecology. All rights reserved. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either version may be used in citing this article. See also the editorial by Scoutt and Norton in this issue.

A Lexicon for First-Trimester US: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

The Society of Radiologists in Ultrasound convened a multisociety panel to develop a first-trimester US lexicon based on scientific evidence, societal guidelines, and expert consensus that would be appropriate for imagers, clinicians, and patients. Through a modified Delphi process with consensus of at least 80%, agreement was reached for preferred terms, synonyms, and terms to avoid. An intrauterine pregnancy (IUP) is defined as a pregnancy implanted in a normal location within the uterus. In contrast, an ectopic pregnancy (EP) is any pregnancy implanted in an abnormal location, whether extrauterine or intrauterine, thus categorizing cesarean scar implantations as EPs. The term pregnancy of unknown location is used in the setting of a pregnant patient without evidence of a definite or probable IUP or EP at transvaginal US. Since cardiac development is a gradual process and cardiac chambers are not fully formed in the first trimester, the term cardiac activity is recommended in lieu of 'heart motion' or 'heartbeat.' The terms 'living' and 'viable' should also be avoided in the first trimester. 'Pregnancy failure' is replaced by early pregnancy loss (EPL). When paired with various modifiers, EPL is used to describe a pregnancy in the first trimester that may or will not progress, is in the process of expulsion, or has either incompletely or completely passed.

Acute heart failure (AHF) in pregnancy and postpartum: Echocardiographic findings from an Indian population

Acute heart failure (AHF) in pregnancy and postpartum: Echocardiographic findings from an Indian population

Predicting the pregnancy outcome: Uncovering the link between β-hCG, patient factors and live birth in IVF

ObjectiveThe objectives of the study were to correlate live birth rate with the initial level of β-hCG in all patients undergoing embryo transfer and develop a predictive model of live birth based on patients’ and assisted reproductive technology (ART) characteristics. Study designSingle-center retrospective cohort study, including a total of 7587 positive first serum β-hCG from women who performed fresh and frozen embryo transfer.Twenty-one variables related to patient characteristics and treatment modalities were analyzed by step-wise univariate analysis followed by multivariate analysis. The study included women between 18 and 45 years with a positive (>20 IU/L) serum β-hCG between January 2011 and December 2020 while it excluded cycles from donation of gametes, PGT and >3 embryos transferred simultaneously. Main results and the role of chance: Among the positive serum β-hCG measurements 5085 (67.0 %) resulted in live births. β-hCG was higher in the live birth group (691 IU/L) compared to the failed pregnancies group (304 IU/L) (p500 IU/mL provided a positive predictive value for live birth of 85.3 % (95 %CI 84.0–86.4).Failed pregnancies were more common among older maternal and paternal age. Previous abortions were more common in the failed pregnancies group (25.0 %) compared to the live birth group (19.4 %). The most common indication to treatment was male infertility, accounting for a larger portion in the live birth group (41.7 %). At multivariate analysis, the factors independently associated with live birth were: first serum β-hCG (OR 1.35, 95 %CI 1.32–1.37), maternal age (OR 0.93, 95 %CI 0.91–0.95), previous abortions (OR 0.77, 95 % CI 0.68–0.88). The number of embryos transferred showed a positive correlation below a maternal age of 39 (<35 years old OR 1.60, CI 95 % 1.32–1.94; <39 years old OR 1.27 CI 95 % 1.09–1.47). The prediction model incorporating these four variables resulted in a sensitivity and specificity with an area under the ROC curve of 0.798. Conclusion: The study confirms the importance of the first value of β-hCG and proposes a predictive model that takes into account maternal age, number of embryos transferred, and obstetric history, thereby aiding in couples’ counseling and ultimately improve patients’ care.

Navigating allergies safely: tailored solutions in special circumstances – a comprehensive review of antihistamines

Personalised medicine is critical in managing allergic diseases, with the variety of second-generation antihistamines necessitating tailored approaches to individual patient needs. This encompasses considerations of age, pregnancy, breastfeeding, hepatic and renal failure, drug interactions, and aging. This paper synthesises current research and guidelines on the use of antihistamines across diverse clinical scenarios, paying special attention to paediatric allergy treatment, including safety profiles of first- and second-generation antihistamines, their use during pregnancy, breastfeeding, and interactions with other drugs, as well as considerations for elderly patients. Second-generation antihistamines are preferred for allergy treatment due to their safety, minimal adverse effects, and efficacy, with a strong recommendation against the use of first-generation antihistamines due to their potential to induce severe adverse reactions. Cetirizine, levocetirizine, and desloratadine are favoured in infants; whereas loratadine, rupatadine, and bilastine are recommended for preschoolers and older children. The safety of selected second-generation antihistamines during pregnancy (notably cetirizine, levocetirizine, desloratadine) and breastfeeding (notably loratadine, desloratadine, fexofenadine), in patients with renal failure and elderly patients (bilastine, desloratadine, fexofenadine), and patients with hepatic failure (bilastine, fexofenadine) is highlighted. The choice of second-generation antihistamines should be based on the patients’ individual needs and conditions to achieve optimal therapeutic outcomes and ensure safety, emphasising the importance of drug selection in varying clinical contexts.

O-307 Decrease of human sperm hypercondensed chromatin volume after slow freezing revealed by three-dimensional (3D) nuclear morphometry

Abstract Study question Are the 3D morphometry parameters of the human sperm nucleus affected by slow freezing? Summary answer The slow freezing-thawing cycle induces significant alterations on hypercondensed nucleus zone by reducing its volume and splits it into several small zones. What is known already Sperm cryopreservation is an essential technique for infertility care, but it seems to highly affect the genetic and epigenetic integrity of sperm nuclei with poorly identified mechanisms. Moreover, it is known that sperm nuclear alterations may be involved in pregnancy failures. Therefore, sperm nuclear biomarkers are an essential issue to assess the outcome of ART procedures when frozen sperm is used. Thereby, 3D visualization of chromatin is a good way to understand modifications in the organization and composition of sperm chromatin after a slow freezing procedure. Study design, size, duration Ten semen of patients were analyzed (Germetheque biobank) after informed consent. Standard semen parameters, DNA fragmentation, chromatin decondensation, sperm telomere length (STL) and 3D nuclear morphometry were performed before and after slow freezing. Morphometric measurements were performed from a digital representation of the sperm nucleus in 3 dimensions that allow us to measure the volume, flatness and elongation of each sperm nucleus and characterize hypercondensed zones, with live/dead spermatozoa distinction. Participants/materials, setting, methods After addition of cryoprotective medium v/v (Cryosperm®), sperm was frozen with a programmable freezer (NanoDigitcool®). Standards sperm parameters were measured in accordance with WHO guidelines 2021, DNA fragmentation by flow cytometry TUNEL assay, chromatin decondensation by epifluorescent microscopy with Chromomycin A3 and STL using qPCR. 3D nuclear representation was performed by a z-axis image acquisition series of DAPI/PI stained slides with optigrid epifluorescent microscopy. Analyses were carried out using the NucleusJ2.0 software with NODeJ plugin. Main results and the role of chance Freezing induces an alteration of sperm vitality (p &amp;lt; 0.0001) and progressive and total motility (p &amp;lt; 0.001 and p &amp;lt; 0.0001 respectively) and an increase in the percentage of sperm with DNA fragmentation (18.30% fresh vs 31.6% frozen, p &amp;lt; 0.05). We did not observe a modification of the median volume of the sperm nucleus before and after freezing (37.15 [IC = 36.5;38.14] and 37.10 [33.27;37.78] µm3 respectively), as the same for flatness and elongation (2.48 vs. 2.50 a.u. and 2.04 vs. 2.04 a.u. respectively). Nevertheless, five samples showed significant alterations of nucleus volume (p &amp;lt; 0.0001), due to diminution of flatness and more or less elongated. A significant decrease of the total volume of the hypercondensed chromatin zone was observed after freezing (0.94 [0.84;0.99] before vs. 0.61 [0.53;0.69] µm3 after freezing-thawing, p &amp;lt; 0.0001), with an effect size of -1.48 [-2.10; -0.86]. Decrease of total volume of hypercondensed region was measured homogeny in all the samples tested, particularly on live (1.00 vs. 0.68 µm3 respectively, p &amp;lt; 0.0001) compared with dead spermatozoa (0.72 vs. 0.57 µm3, p &amp;lt; 0.05). We showed also a significant increase of the number of hypercondensed zones in each nucleus (p &amp;lt; 0.001), reflecting a split into several parts of the hypercondensed chromatin. Limitations, reasons for caution A 3D-FISH analysis would allow to characterize the hypercondensed chromatin portion, probably as heterochromatin and which we suspect to be the nucleus ring. Moreover, a chromosomes specific marking would allow for the identification of whether whole chromosomes or specific parts of chromosomes (centromeres or telomeres) are affected by this decompaction. Wider implications of the findings This study is the first to make exacts measurements of human sperm nucleus because of a non-decondensing method. We demonstrate that slow freezing affects hypercondensed chromatin probably through a decondensation and modification of the nucleus-specific organization. This new assessment will allow a better proficiency of men fertility preservation techniques. Trial registration number NCT04715828