Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Laparoscopic Management of a 12-Week Pregnancy Loss in a Rudimentary Uterine Horn.

Unicornuate uterus with rudimentary horn is a rare structural uterine anomaly resulting from incomplete Mullerian duct development and/or fusion. Pregnancy in rudimentary horn is an uncommon presentation of a Mullerian anomaly and may lead to substantial morbidity and mortality due to high risk of uterine rupture with intraabdominal hemorrhage. Medical and/or surgical management may be undertaken; however, currently, no treatment guidelines exist. We describe the management of a 12-week rudimentary horn pregnancy in a 25-year-old multiparous patient with a prior spontaneous preterm breech vaginal delivery and one spontaneous early term cephalic vaginal delivery in whom this congenital uterine condition was previously unknown. The rudimentary horn, nonviable pregnancy, and contiguous ipsilateral fallopian tube were excised laparoscopically without complication. Given the infrequency of rudimentary horn pregnancies and the high risk for obstetric complications, a high index of suspicion should be maintained. We emphasize that a history of preterm birth or malpresentation should raise suspicion for maternal Mullerian anomaly, and that a minimally invasive approach can be feasible for treatment of a rudimentary horn pregnancy.

Altered N6-methyladenosine methylation level in spermatozoa messenger RNA of the male partners is related to unexplained recurrent pregnancy loss.

BACKGROUND: Understanding the pathogenesis of unexplained recurrent pregnancy loss is paramount for advancing effective treatments. Various biological processes, including spermatogenesis and embryo development, are tightly regulated by N6-methyladenosine modifications. However, few studies have focused on the impact of sperm N6-methyladenosine modifications on embryonic development. Therefore, we aimed to study altered N6-methyladenosine-mediated messenger RNA methylation modifications in the spermatozoa of male partners from couples experiencing unexplained recurrent pregnancy loss, to identify potential diagnostic markers and explore their potential molecular mechanisms in pregnancy loss and embryogenesis. METHODS: Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were conducted on the spermatozoa of men from couples in the 'unexplained recurrent pregnancy loss' group (n = 6), and the fertility control group (n = 6). To identify the role of the detected key genes, zebrafish model embryos were studied, and multi-omics (transcriptomics, proteomics, and metabolomics) analyses helped to explore the molecular mechanism of abnormal embryogenesis. FINDINGS: Comparing unexplained recurrent pregnancy loss with the fertility control group, 217 N6-methyladenosine peaks were significantly upregulated, and 40 were downregulated in the spermatozoa. The combined analyses of spermatozoa-methylated RNA immunoprecipitation sequencing and RNA sequencing indicated that N6-methyladenosine methylation and the expression of SEMA5A, MT-ATP6, ZNF662, and KDM4C were significantly different. In zebrafish embryos, the altered expression of the four genes increased embryonic mortality and malformations by disturbing several key signaling pathways and zygotic genome activation. INTERPRETATION: This study highlights the paternal epigenome, which could be one of the reasons for faulty embryogenesis leading to pregnancy loss. The N6-methyladenosine modification, the most prevalent RNA modification, contributes to the exploration and understanding of the paternal epigenome in the maintenance of pregnancy and fetal growth and development. The four genes identified in this study may serve as potential diagnostic markers and elucidate novel molecular mechanisms of embryogenesis.

The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

STUDY QUESTION: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? SUMMARY ANSWER: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. WHAT IS KNOWN ALREADY: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). LIMITATIONS, REASONS FOR CAUTION: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Double cervical cerclage for cervical insufficiency: Case report.

Recurrent pregnancy loss devastates parents and frustrates doctors, especially when the pregnancy progresses to the second trimester. Cervical insufficiency is the most common cause of second-trimester pregnancy loss. Abdominal cerclage is the treatment option for women with failed vaginally applied cervical cerclage. We report a 33-year-old para 0 with a history of nine second-trimester pregnancy losses. She had six failed transvaginal cerclages using McDonald's procedure. A vaginal double cervical cerclage was placed in her index pregnancy. Two mersilene tape purse-string sutures were placed in the submucosal layer of the cervix; the first 1cm below and the second at the level of the internal os. Both sutures were knotted at the 12 O'Clock position on the cervix. She carried her pregnancy to almost term and delivered a healthy baby girl weighing 2.5kg. We recommend a transvaginal double cervical cerclage with mersilene tape using a modified McDonald's technique as a viable alternative to abdominal cervical cerclage. (Afr J Reprod Health 2024; 28 [6]: 117-125).

Les fausses couches récurrentes sont dévastatrices pour les parents et frustrent les médecins, surtout lorsque la grossesse progresse jusqu'au deuxième trimestre. L'insuffisance cervicale est la cause la plus fréquente de fausse couche au deuxième trimestre. Le cerclage abdominal est l'option de traitement pour les femmes dont le cerclage cervical appliqué par voie vaginale a échoué. Nous rapportons une para 0 de 33 ans avec des antécédents de neuf fausses couches au deuxième trimestre. Elle a eu six cerclages transvaginaux selon la procédure McDonald's qui ont échoué. Un double cerclage vaginal vaginal a été placé lors de sa grossesse index. Deux fils de suture en bourse en ruban de mersilène ont été placés dans la couche sous-muqueuse du col de l'utérus ; le premier 1cm en dessous et le second au niveau de l'os interne. Les deux sutures ont été nouées à la position 12 heures sur le col. Elle a mené sa grossesse presque à terme et a donné naissance à une petite fille en bonne santé pesant 2,5 kg. Nous recommandons un double cerclage cervical transvaginal avec du ruban de mersilène en utilisant une technique McDonald's modifiée comme alternative viable au cerclage cervical abdominal. (Afr J Reprod Health 2024; 28 [6]: 117-125).

Impact of first-trimester mechanical cervical dilatation during curettage on maternal and neonatal outcomes: A retrospective comparative study.

OBJECTIVE: Earlier studies have indicated a potential link between dilatation and curettage (D&C) and subsequent preterm delivery, possibly attributed to cervical damage. This study examines outcomes in pregnancies subsequent to first-trimester curettage with and without cervical dilatation. METHODS: A retrospective cohort study was conducted on women who conceived after undergoing curettage due to a first trimester pregnancy loss. Maternal and neonatal outcomes of the subsequent pregnancy were compared between two groups: women who underwent cervical dilatation before their curettage and those who had curettage without dilatation. The primary outcome assessed was the rate of preterm delivery at the subsequent pregnancy, and secondary outcomes included other adverse maternal and neonatal outcomes. Univariate analysis was performed, followed by multiple logistic regression models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Among the 1087 women meeting the inclusion criteria during the study period, 852 (78.4 %) underwent first-trimester curettage with cervical dilatation, while 235 (21.6 %) opted for curettage only. No significant maternal or neonatal different outcomes were noted between the study groups, including preterm delivery (5.5 % vs. 3.5 %, p = 0.16), fertility treatments, placental complications, and mode of delivery. However, deliveries following D&C were associated with higher rates of small for gestational age neonates (7.6 % vs. 3.8 %, p = 0.04). Multivariate analysis revealed that cervical dilation before curettage was not significantly linked to preterm delivery [adjusted odds ratio 0.64 (0.33-1.26), p = 0.20]. CONCLUSION: The use of cervical dilatation during a curettage procedure for first trimester pregnancy loss, does not confer additional risk of preterm delivery. Further studies are needed to reinforce and validate these results.

Associations of Nutrients and Dietary Preferences with Recurrent Pregnancy Loss and Infertility.

This review examines associations of nutrients and dietary preferences with recurrent pregnancy loss (RPL), miscarriage, and infertility. Research articles, reviews, and meta-analyses of RPL and infertility that focused on nutrition, meals, and lifestyle were reviewed, and associations of nutrients and dietary preferences with pregnancy are discussed in relation to recent research findings. Studies related to RPL were given the highest priority, followed by those dealing with miscarriage and infertility. Multivitamin supplements-even when lacking folic acid or vitamin A-reduced total fetal loss. High-dose folic acid supplementation before conception reduced the risk of miscarriage and stillbirth. A meta-analysis revealed a strong association of vitamin D deficiency/insufficiency with miscarriage. Another meta-analysis revealed that seafood and dairy products reduced the risk of miscarriage, whereas a caffeine intake of 300 mg/day or more was associated with miscarriage. A balanced diet that included nutrients with antioxidant properties helped prevent miscarriage, whereas a diet that included processed foods and nutrients with proinflammatory effects increased the risk of miscarriage. Associations of nutrients with RPL warrant further research.

Telemedicine Follow-up After Medication Management of Early Pregnancy Loss.

Objective: Our objective was to evaluate the feasibility of a new protocol for telemedicine follow-up after medication management of early pregnancy loss. Study Design: The study was designed to assess the feasibility of planned telemedicine follow-up after medication management of early pregnancy loss. We compared these follow-up rates with those after planned in-person follow-up of medication management of early pregnancy loss and planned telemedicine follow-up after medication abortion. We conducted a retrospective cohort study, including patients initiating medication management of early pregnancy loss <13w0d gestation and medication abortion ≤10w0d with a combination of mifepristone and misoprostol between April 1, 2020, and March 28, 2021. As part of a new clinical protocol, patients could opt for telemedicine follow-up one week after treatment and a home urine pregnancy test 4 weeks after treatment. Our primary outcome was completed follow-up as per clinical protocol. We also examined outcomes related to complications across telemedicine and in-person follow-up groups. Results: Of patients reviewed, 181 were eligible for inclusion; 75 had medication management of early pregnancy loss, and 106 had medication abortion. Thirty-six out of 75 patients elected for telemedicine follow-up after early pregnancy loss. Of patients scheduled for telemedicine follow-up, 29/36 (81%, 95% CI: 64-92) with early pregnancy loss and 64/69 (93%, 95% CI: 84-98) undergoing medication abortion completed follow-up as per protocol (p = 0.06). Completed follow-up was also similar among patients undergoing medication management of early pregnancy loss who planned for in-person follow-up (p = 0.135). Complications were rare and did not differ across early pregnancy loss and medication abortion groups. Conclusions: Telemedicine follow-up is a feasible alternative to in-person assessment after medication management of early pregnancy loss.

Correlation of Anti-Phosphatidylserine/Prothrombin and Anti-Phosphatidylserine Antibodies with Pregnancy Outcomes.

BACKGROUND: The objective of this study was to investigate the clinical relevance of anti-prothrombin antibodies (aPT) and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in relation to pregnancy outcomes and coagulation parameters, as well as immune markers. METHODS: We retrospectively analyzed 477 pregnant women with experienced at least one spontaneous miscarriage who were tested for aPT and aPS/PT antibodies, and compared their clinical characteristics, coagulation indicators, immune biomarkers, and pregnancy outcomes to assess the diagnostic accuracy of these antibodies. RESULTS: We found that the aPT IgG and the aPS/PT IgM were independently associated with increased risk of pregnancy loss, with odds ratios (ORs) of 1.055 (95% confidence interval [CI]: 1.009-1.103, p = 0.017) and 1.041 (95% CI: 1.015-1.067, p = 0.002), respectively. Moreover, we found that the aPS/PT IgM had a higher diagnostic performance than the aPT IgG, as indicated by the AUC of 0.663 and 0.593, respectively. The pregnancy loss rate was positively correlated with the level of aPS/PT IgM, while the aPT IgG is not. We also found that in the pregnancy loss group, aPT IgG showed negative correlations with prothrombin time (PT); aPS/PT IgM showed positive correlations with aPS/PT IgG. However, none of aPT IgG, aPT IgM, aPS/PT IgM, or aPS/PT IgG was related to other adverse pregnancy outcomes, such as preterm delivery, fetal growth restriction (FGR), or preeclampsia (PE). CONCLUSION: Our findings suggest that aPT IgG and aPS/PT IgM are independent risk factors for pregnancy loss, especially aPS/PT IgM, which has a positive linear correlation with pregnancy loss.

Predicting risk of the subsequent early pregnancy loss in women with recurrent pregnancy loss based on preconception data.

BACKGROUND: For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. RESULTS: In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer-Lemeshow test was 7.427, and P = 0.505. CONCLUSIONS: Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Association between human papillomavirus and preterm delivery: A systematic review and meta-analysis.

INTRODUCTION: The lifetime prevalence of human papillomavirus infection (HPV) is estimated to be around 80% and it is the most common sexually transmitted infection. Despite being well known for its oncologic relevance, it has been associated with adverse pregnancy outcomes, though available evidence is contradicting. Previous meta-analyses involved articles which based HPV infection on Pap smear results, leading to a significant source of bias. Therefore, we aimed to assess the burden of genetically proven HPV infection on adverse pregnancy outcomes. MATERIAL AND METHODS: In our meta-analysis, pregnant women tested for HPV DNA were only considered eligible. We conducted a systematic search in three major databases (PubMed, Embase, and CENTRAL) on September 22, 2023. Cohort, cross-sectional, and case-control studies were eligible for the analysis. The exposed group consisted of HPV-infected patients. We assessed the odds ratios (OR) with a confidence interval (CI) of 95%. In order to reduce the heterogeneity, we performed subgroup analyses based on different strains (high risk HPV, HPV 16/18, study design). The study was prospectively registered on PROSPERO (CRD42022370228). RESULTS: Our study involved 14 articles with 7008 women. A significant association was found between preterm delivery and HPV infection (OR: 1.94, CI: 1.31-2.87). No significant association was found when separately examining high-risk HPV-infected women (OR: 1.94, CI: 0.82-4.59), and HPV 16 or 18-infected women (OR: 2.08, CI: 0.50-8.63) in terms of preterm delivery. No significant association was found between spontaneous abortion and HPV infection (OR: 1.02, CI: 0.16-6.31). CONCLUSIONS: Our analysis indicates an association between HPV infection and preterm delivery. It is imperative that future studies consider confounding variables more comprehensively. Additionally, the global implementation of HPV vaccination programs holds significance not only in oncology but also in obstetrics.

Are Altered Expression of Vascular Endothelial Growth Factor and Placental Growth Factor Associated with Placental Angiogenesis in Recurrent Pregnancy Loss?

Angiogenesis is one of the most important steps during pregnancy for placental and fetal development. Based on the hypothesis that vascular insufficiency and altered angiogenesis may lead to early pregnancy loss, the present study was aimed to understand the role of Vascular endothelial growth factor (VEGFA) and Placental growth factor (PLGF) gene expression in placental angiogenesis in the pathogenesis of Recurrent pregnancy loss (RPL). Gene expression analysis of VEGFA and PLGF was carried out in the placental tissue collected from 30 women with recurrent pregnancy loss and compared with the placenta obtained from 16 women with medically terminated pregnancy. The mRNA expression of both VEGFA and PLGF genes were significantly downregulated in the placenta of recurrent pregnancy loss in comparison to the placenta of medically terminated pregnancies. In conclusion the results of the present study suggest that altered expression of VEGFA and PLGF genes in placenta disturb the angiogenesis and contribute to the pathogenesis of recurrent pregnancy loss.

"If it has happened once, it can happen again". The impact of previous pregnancy loss on anxious women's ongoing pregnancies: A qualitative study from Pakistan.

BACKGROUND: Pregnancy loss that includes both miscarriage and stillbirth cause significant psychological distress for women including anxiety, depression, and grief that persist long after physical recovery. This study focuses on the experiences of women in Pakistan, where pregnancy loss rates are high. OBJECTIVE: To explore how pregnant women with anxiety symptoms and a history of pregnancy loss perceive their past experiences with the loss and how it affects overall well-being in their current pregnancy. DESIGN: Qualitative methods were used to explore the impact of previous pregnancy loss on the well-being of pregnant women. SETTING: This qualitative research was embedded within a randomized control trial conducted in a tertiary care facility in Rawalpindi, Pakistan. PARTICIPANTS: Data were collected through in-depth interviews with 18 pregnant women who had experienced pregnancy loss. Data was analyzed using Framework Analysis. FINDINGS: The findings revealed several factors influencing participants' well-being during pregnancies that resulted in a loss, such as unsupportive and abusive environments, unintended pregnancies, certain superstitious beliefs, poor health, and lack of access to quality healthcare. The study also highlighted the adverse impact of previous pregnancy loss on the ongoing pregnancy, including deterioration of physical and mental health and aversion of healthcare services. However, some participants reported positive changes in medical and self-care practices and an enhanced faith and reliance on destiny in their subsequent pregnancies. CONCLUSION: Our study highlights the lasting impact of past pregnancy loss on subsequent pregnancies, affecting overall wellbeing and leading to healthcare avoidance. We identified persistent anxiety along with positive outcomes like enhanced medical practices and strengthened faith. Results suggest the need for culturally responsive interventions to support the overall well-being of anxious pregnant women with a history of pregnancy loss in resource-constrained settings.

The Success of Mifepristone and Misoprostol in the Management of Early Pregnancy Loss at a Community Hospital: A Prospective Study.

BACKGROUND: This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL). METHODS: We recruited 441 participants; 188 met eligibility criteria. Participants were 18 years of age and older who experienced a confirmed early pregnancy loss (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pretreatment orally followed by two doses of misoprostol 800 mcg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage (D & C). We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events. RESULTS: 181 participants followed the protocol, and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and one had an adverse event of heavy vaginal bleeding requiring D & C. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium. CONCLUSION: Pretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.

Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: a meta-analysis of cohort studies.

PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.

An Overview of Infectious and Non-Infectious Causes of Pregnancy Losses in Equine.

Equine breeding plays an essential role in the local economic development of many countries, and it has experienced rapid growth in China in recent years. However, the equine industry, particularly large-scale donkey farms, faces a significant challenge with pregnancy losses. Unfortunately, there is a lack of systematic research on abortion during equine breeding. Several causes, both infectious and non-infectious, of pregnancy losses have been documented in equines. The infectious causes are viruses, bacteria, parasites, and fungi. Non-infectious causes may include long transportation, ingestion of mycotoxins, hormonal disturbances, twinning, placentitis, umbilical length and torsion, etc. In current review, we discuss the transmission routes, diagnostic methods, and control measures for these infectious agents. Early detection of the cause and appropriate management are crucial in preventing pregnancy loss in equine practice. This review aims to provide a comprehensive understanding of the potential causes of abortion in equines, including infectious agents and non-infectious factors. It emphasizes the importance of continued research and effective control measures to address this significant challenge in the equine industry.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

Fertility outcomes in women undergoing Assisted Reproductive Treatments after COVID-19 vaccination: A prospective cohort study.

BACKGROUND: Vaccination against Coronavirus-19 disease (COVID-19) was widely administered from 2021 onwards. There is little information on how this vaccine affected fertility after assisted-reproductive-technology (ART). The aim of this study therefore was to determine if COVID-19 vaccination or time-since-vaccination influenced ART outcomes. MATERIALS AND METHODS: In this prospective cohort study, 502 oocyte-retrieval-cycles and 582 subsequent embryo- transfer-cycles were grouped based on COVID-19 vaccine status of the female partner into those with no-exposure, 1-dose and ≥2-dose exposure. Within the exposed cohort, time-since-last-vaccination to embryotransfer- cycle (Ttr) was calculated in days. Main outcomes were mean-total-utilizable-embryos, mean-oocyteutilization- rates and cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle, and ongoing-pregnancy and pregnancy-loss-rates per embryo-transfer cycle. The Beta-coefficient (ß) was calculated using linear regression for mean-total-utilizable-embryos and mean-oocyte-utilization-rates and adjusted-odds-ratio (OR) was calculated for cumulative-ongoing-pregnancy-rates, ongoing-pregnancy and pregnancy-loss-rates using binomial logistic regression. Influence of T(tr) on embryo-transfer outcomes was estimated using receiver-operator-curve (ROC) analysis and cut-offs determined that influenced embryo-transfer outcomes. RESULTS: Mean-total-utilizable-embryos and mean-oocyte-utilization-rate per oocyte-retrieval-cycle in no-exposure, 1-dose and ≥2 dose were 2.7 ± 1.8 vs. 2.5 ± 1.9 vs. 2.7 ± 2.0, P=0.78, (ß=0.42, 95% confidence-interval (CI)=0.15 to 0.69) and 21.2 ± 13.2 vs. 25.1 ± 19.0 vs. 26.7 ± 18.8, P=0.08, (ß=3.94, 95% CI=1.26 to 6.23) respectively. Ongoing-pregnancy-rates and pregnancy-loss-rates per embryo-transfer-cycle were 27.3% vs. 24.4% vs. 32.5% (aOR=1.38, 95% CI=0.3-5.6, P=0.52), and 13.6% vs. 13.4% vs. 15.2%, (aOR=0.97, 95% CI=0.18-5.2, P=0.97) respectively. Cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle were 36.5% vs. 34.5% vs. 35.5% (aOR=1.53, 95% CI=0.57 to 4.07, P=0.35). Median T(tr) was 146 days (IQR: 80-220). T(tr) negatively affected ongoing pregnancy rates for intervals <60 days (AUC=0.59, 95% CI=0.54-0.66, P<0.01). For T(tr) >60 vs. <60 days, the aOR for ongoing-pregnancy-per-embryo-transfer-cycle was 2.85 (95% CI=1.50-5.46, P<0.01). CONCLUSION: Covid-19 vaccination does not negatively influence embryological-outcomes or cumulative-ongoing-pregnancies after ART-treatments. Duration since vaccination may have a weak negative effect on embryo-transfer-outcomes performed within 60 days.

Support sought and offered online for miscarriage: content analysis of a Facebook miscarriage support group.

OBJECTIVE: Responses to miscarriage can vary, with many, but not all, people describing inadequate support, feelings of isolation and significant psychological distress. Limited knowledge exists about the support that people seek and offer online following miscarriage. We aimed to explore how people impacted by miscarriage use an online Facebook support group to seek and offer support. METHODS AND MEASURES: We employed directed content analysis to examine 270 opening posts and 3,484 responding comments within an 'open' Facebook support group for miscarriage. Opening posts and responding comments were coded into five social support categories using an existing support framework. RESULTS: Informational Support, particularly medical information or advice, was the most commonly sought support in opening posts, followed by Emotional Support, where people expressed their grief-related feelings. In responding comments, Emotional Support and Informational Support were predominantly offered. CONCLUSION: While not a substitute for appropriate medical care, people impacted by miscarriage seek and offer support online. Health professionals should be aware of this behaviour and discuss potential benefits and risks of online support with patients. A social support framework may usefully guide health professionals in identifying patients' support needs and in knowing how to support patients.

[Analysis of Risk Factors for Recurrent Pregnancy Loss in Patients Undergoing in vitro Fertilization-Embryo Transfer]. / 体外受精-èƒšèƒŽç§»æ¤æ‚£è€ ä¸­åå¤å¦Šå¨ ä¸¢å¤±çš„å±é™©å› ç´ åˆ†æž.

Objective: Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing in vitro fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a focal point for scientific inquiry. This study endeavors to investigate the intricate interplay between clinical features, such as age, body mass index (BMI), and waist-to-hip ratio (WHR), and routine laboratory parameters, including sex hormones, blood composition, liver and thyroid functions, thyroid antibodies, and coagulation indicators, in RPL patients undergoing IVF-ET. By meticulously analyzing these variables, we aim to uncover the latent risk factors predisposing individuals to RPL. Identifying potential factors such as advanced maternal age, obesity, and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence. Methods: This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2012 and March 2021 as the case cohort, compared with women receiving assisted reproductive treatment due to male infertility as the control cohort. The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion. The clinical characteristics and relevant laboratory indexes of the two groups were compared. Employing both univariate and multivariate logistic regression analyses, we sought to unearth potential high-risk factors underlying RPL. Additionally, a linear trend analysis was conducted to assess the linear relationship between total testosterone (TT) levels and the number of miscarriages. Results: In contrast to the control cohort, the RPL cohort exhibited significant increases in age, BMI, and WHR (P<0.05). Notably, TT levels were markedly lower in the RPL cohort (P=0.022), while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin levels, and anti-Müllerian hormone levels (P>0.05). Moreover, fasting insulin (FINS) levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort (P<0.001), although no significant differences were observed in fasting blood glucose levels (P>0.05). Furthermore, the neutrophil (NEU) count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort (P<0.01). Univariate logistic regression analysis identified several factors, including age≥35 years old, BMI≥25 kg/m2, WHR>0.8, FINS>10 mU/L, HOMA-IR>2.14, NEU count>6.3×109 L－1, and an elevated NEU/lymphocyte ratio (NLR), as significantly increasing the risk of RPL (P<0.05). Although TT levels were within the normal range for both cohorts, higher TT levels were associated with a diminished RPL risk (odds ratio [OR]=0.67, 95% confidence interval [CI]: 0.510-0.890, P=0.005). After adjustments for confounding factors, age≥35 years old (OR=1.91, 95% CI: 1.06-3.43), WHR>0.8 (OR=2.30, 95% CI: 1.26-4.19), and FINS>10 mU/L (OR=4.50, 95% CI: 1.30-15.56) emerged as potent risk factors for RPL (P<0.05). Conversely, higher TT levels were associated with a reduced RPL risk (OR=0.59, 95% CI: 0.38-0.93, P=0.023). Furthermore, the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages (P trend=0.003), indicating a declining trend in TT levels with escalating miscarriage occurrences. Conclusion: In patients undergoing IVF-ET, advanced maternal age, lower TT levels, increased WHR, and elevated FINS levels emerged as potent risk factors for RPL. These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.