Predictors of successful expectant and medical management of miscarriage: A systematic review.

INTRODUCTION: 15.3% of pregnancies result in miscarriage, management options include expectant, medical, or surgical. However, each patient has a range of variables, which makes navigating the available literature challenging when supporting individual patient decision-making. This systematic review aims to investigate whether there are any specific predictors for miscarriage management outcome. MATERIAL AND METHODS: The following databases were searched, from the start of each database up to April 2023: PubMed, Medline, and Google Scholar. Inclusion criteria were studies interrogating defined predictors for expectant or medical management of miscarriage success. Exclusion criteria were poor quality, review articles, trial protocols, and congress abstracts. Data collection was carried as per PRISMA guidelines. Quality assessment for each study was assessed using the QUIPS proforma. RESULTS: Relevant predictors include demographics, ultrasound features, presenting symptoms, and biochemical markers. Across the 24 studies there is heterogeneity in miscarriage definition, predictors reported, and management outcomes used. Associations with certain variables and miscarriage management outcomes are described. Ten studies assessed the impact of miscarriage type on expectant and/or medical management. The majority found that a diagnosis of incomplete miscarriage had a higher success rate following expectant or medical management compared to missed miscarriage or anembryonic pregnancy. CONCLUSIONS: We conclude that there is evidence supporting the possibility to offer personalized miscarriage management advice with case specific predictors. Further larger studies with consistent definitions of predictors, management, and outcomes are needed in order to better support women through the decision-making of miscarriage management.

Medical management of first trimester missed miscarriages - A cross-sectional study.

Background & Objective: Miscarriage, a common complication of early pregnancy before 12 completed weeks of gestation, is typically managed medically. We aimed to estimate the success and complication rate of medical management in women with first-trimester missed miscarriages. Our objective was to calculate the rate of complete uterine evacuation within three weeks of treatment, rate of infection, significant blood loss, re-admission, or surgical evacuation. Methods: It was a retrospective cross-sectional study that included women diagnosed with miscarriage at less than 13 weeks' gestation in Latifa Hospital's Gynecology Department from January 2019 to December 2019 in Dubai. These patients were given vaginal misoprostol, 400-800 mcg every 6-8 hours until expulsion of pregnancy. Results: There were 294 women included in the study. The success rate was 60.5% (178/294). Twenty women developed significant blood loss (6.8%), four women developed infection (1.4%), 76 required readmission (25.9%), 12 women received blood transfusion (4.1%), and 74 women required a surgical evacuation (25.2%). Nulliparity, unscarred uterus, and the presence of abdominal pain with vaginal bleeding before treatment were significantly associated with the successful medical treatment (p<0.05). Conclusion: The success rate of the medical regimen studied lies on the lower end of what is quoted in the literature. The difference in the success rate could be attributed to the different definitions of success in other studies. Nulliparity, unscarred uterus and presence of abdominal pain with vaginal bleeding were associated with higher success.

IL-2/JES6-1 antibody complex expands the maternal T regulatory cell pool and alleviates fetal loss in abortion-prone mice.

Regulatory T (Treg) cells are essential for immune tolerance of embryo implantation and insufficient Treg cells are implicated in early pregnancy loss. An abortion-prone mouse model was utilized to evaluate the utility of IL-2 complexed with JES6-1 anti-IL-2 antibody (IL-2/JES6-1) to boost uterine Treg cells and improve reproductive success. IL-2/JES6-1 but not IL-2/IgG control administered in the peri-conception phase to CBA/J females mated with DBA/2 males elicited a >2-fold increase in the proportion of CD4+ T cells expressing FOXP3, and an increase in the ratio of FOXP3+ Treg cells to FOXP3- T conventional cells, in the uterus and its draining lymph nodes at embryo implantation that was sustained into mid-gestation. An attenuated phenotype was evident in both thymic-derived and peripheral Treg cells with elevated CTLA4, CD25, and FOXP3 indicating improved suppressive function, as well as increased proliferative marker Ki67. IL-2/JES6-1 treatment reduced fetal loss from 31% to 10%, but this was accompanied by a 6% reduction in late gestation fetal weight, despite comparable placental size and architecture. Similar effects of IL-2/JES6-1 on Treg cells and fetal growth were seen in CBA/J females with healthy pregnancies sired by BALB/c males. These findings show that expanding the uterine Treg cell pool through targeting IL-2 signaling is a strategy worthy of further investigation for mitigating immune-mediated fetal loss.

Preliminary findings on the experiences of care for women who suffered early pregnancy losses during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Women who suffer an early pregnancy loss require specific clinical care, aftercare, and ongoing support. In the UK, the clinical management of early pregnancy complications, including loss is provided mainly through specialist Early Pregnancy Assessment Units. The COVID-19 pandemic fundamentally changed the way in which maternity and gynaecological care was delivered, as health systems moved to rapidly reconfigure and re-organise services, aiming to reduce the risk and spread of SARS-CoV-2 infection. PUDDLES is an international collaboration investigating the pandemic's impact on care for people who suffered a perinatal bereavement. Presented here are initial qualitative findings undertaken with UK-based women who suffered early pregnancy losses during the pandemic, about how they navigated the healthcare system and its restrictions, and how they were supported. METHODS: In-keeping with a qualitative research design, in-depth semi-structured interviews were undertaken with an opportunity sample of women (N = 32) who suffered any early pregnancy loss during the COVID-19 pandemic. Data were analysed using a template analysis to understand women's access to services, care, and networks of support, during the pandemic following their pregnancy loss. The thematic template was based on findings from parents who had suffered a late-miscarriage, stillbirth, or neonatal death in the UK, during the pandemic. RESULTS: All women had experienced reconfigured maternity and early pregnancy services. Data supported themes of: 1) COVID-19 Restrictions as Impractical & Impersonal; 2) Alone, with Only Staff to Support Them; 3) Reduction in Service Provision Leading to Perceived Devaluation in Care; and 4) Seeking Their Own Support. Results suggest access to early pregnancy loss services was reduced and pandemic-related restrictions were often impractical (i.e., restrictions added to burden of accessing or receiving care). Women often reported being isolated and, concerningly, aspects of early pregnancy loss services were reported as sub-optimal. CONCLUSIONS: These findings provide important insight for the recovery and rebuilding of health services in the post-pandemic period and help us prepare for providing a higher standard of care in the future and through any other health system shocks. Conclusions made can inform future policy and planning to ensure best possible support for women who experience early pregnancy loss.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

Medical treatment of miscarriage using misoprostol-a retrospective study.

PURPOSE: The treatment of early miscarriage with medication is effective and low in side effects. Nevertheless, no uniform dosage regimen has yet been established, nor has it been possible to determine whether previous pregnancies and births with their respective modes of delivery play a role in the effectiveness of Misoprostol. This study aimed to find predictive parameters for successful treatment with Misoprostol in early miscarriage. METHODS: In a retrospective study at the Otto von Guericke University Women's Hospital, records of patients with early miscarriage and medical treatment using Misoprostol from 2018 to 2021 were reviewed for this purpose. The need for a curettage subsequent to treatment was scored as a parameter of failure. The data were analyzed using Statistical Package for the Social Science Version 28.0. The significance level was set to 0.050. RESULTS: We found that successful therapy with misoprostol was seen in 86% (n = 114). 14% (n = 20) of the patients had curettage after taking Misoprostol as advised. Out of 134 women, 16% (n = 21) reported mild side effects, with nausea as the leading one (9.2% (n = 12)). Significance was found comparing the measurement of double endometrial stripe thickness after the second cycle of Misoprostol in women with and without curettage after medical treatment (exact value two-sided 0.035 at p < 0.05). A cutoff value at 8.8 mm was calculated using ROC Analysis. CONCLUSIONS: Our results indicate that the treatment of early miscarriage in the first trimester with Misoprostol is effective and has few side effects. The measurement of the endometrial stripe thickness after the second cycle of Misoprostol via transvaginal ultrasound could present a predictive marker during therapy.

Assessing the predictive value of first trimester ultrasound and biochemical markers in miscarriage: A scoping review.

INTRODUCTION: Vaginal bleeding in the first trimester of pregnancy generates anxiety and uncertainty for expecting parents. The ability to determine pregnancy outcome through a first trimester ultrasound scan remains a challenge in obstetrics. Several first trimester ultrasound markers used individually or in combination, as well as ultrasound markers used in combination with biochemical markers, have been studied to determine their predictive value in pregnancy outcome. This scoping review was performed to determine which markers have already been investigated for this purpose. METHODS: An extensive and systematic database search was performed using four different categories of keywords which were combined using Boolean terms. A total of 14 variables were included on the final data charting forms. Data was synthesised collectively for each variable and then separately for the studies analysing only one marker. For the studies which analysed multiple markers, data was synthesised based on the number of markers per study. RESULTS: The search yielded 3608 studies, of which 128 were ultimately used for this review. Data extraction, based on predetermined eligibility criteria, was performed by two authors independently. Seventy-seven (62.6%) studies investigated the predictive value of a single ultrasound marker. The remaining 46 (37.4%) studies explored multiple markers, of which at least one was an ultrasound marker. CONCLUSION: This review identified several discrepancies among different studies. This highlights the need for better consensus among researchers to allow for the design of a predictive model which enables extrapolation of findings to all pregnant women. IMPLICATIONS FOR PRACTICE: Through the study of ultrasound and biochemical markers in the first trimester of pregnancy, clinicians may provide a more accurate prediction of pregnancy outcome following threatened miscarriage.

Impaired Epithelial CD200L Tolerance Signaling in Irritable Bowel Syndrome Cases With Diarrhea May Be Associated With Recurrent Miscarriages.

PROBLEM: There is a higher incidence of irritable bowel syndrome with miscarriages, and recurrent miscarriages of otherwise normal embryos have been linked to subnormal expression of the immune checkpoint inhibitor CD200L. We sought to determine if alterations in the expression of the CD200 immune checkpoint inhibitor occur in colonic tissue in IBS-D patients. METHOD OF STUDY: Quantitative immunohistochemical staining of biopsies from proximal and distal colon or rectum for the inhibitory CD200L and CD200S molecules was done. CD56 cells were also enumerated as they play a role in recurrent miscarriages and may express CD200S. RESULTS: CD200L was decreased and CD200S was unchanged in epithelium but not stroma of 3 IBS-D cases. One case had an increase in both CD200L and CD200S. CD56 cells were also stained for CD200S. Degranulation was assessed by the percentage of extracellular CD200S that was increased as epithelial CD200L decreased. CONCLUSIONS: This pilot study was promising and warrants a larger sample to determine if a correlation between uterine implantation site CD200L and CD200S expression in normal and failing implantation sites is needed. Colonic epithelial CD200L may then provide useful information about the pathogenesis of the spontaneous miscarriage in individual cases.

Cesarean section at full dilatation in the first birth is not associated with an increased risk of subsequent miscarriage: A historical cohort study.

INTRODUCTION: Cesarean section at full dilatation has been associated with an increased risk of subsequent preterm birth. We hypothesized that there may be an increased risk of miscarriage in pregnancies that follow cesarean section at full dilatation. This study aimed to determine if a first-term (≥37 weeks) cesarean section at full dilatation is associated with an increased risk of miscarriage in the next pregnancy. MATERIAL AND METHODS: A historical cohort study was conducted using routinely collected hospital data within the Aberdeen Maternity and Neonatal Databank (AMND). The population included were women who had a first-term birth and who had a second birth recorded within the AMND. Logistic and multinomial regression was used to determine any association with miscarriage at any gestation and for early (<13 weeks gestation) and late (13-23 + 6 weeks gestation) miscarriage, with cesarean section at full dilatation defined as the exposure. Miscarriage in the second pregnancy (spontaneous loss of intrauterine pregnancy prior to 24 weeks gestation) was the primary outcome. RESULTS: In total, 33 452 women were included. Women who had a first cesarean section at full dilatation were no more likely to have a miscarriage at any gestation than women with all other modes of first birth (including all vaginal births, planned CS, and the first stage of labor (<10 cm dilated CS)) [adjusted OR 0.84 (0.66-1.08); p = 0.18]. There was no association with early or late miscarriage after a CSfd, though the sample size for late miscarriage was small. CONCLUSIONS: This is the first observational study to investigate the risk of miscarriage following first-term CSfd. We found no association between miscarriage at any gestation following a first-term CSfd compared to all other modes of first birth.

Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality.

Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.

Utility of culture and molecular methods using AllplexTM Bacterial Vaginosis Plus Assay (SeegeneⓇ) as a tool for endometriosis, infertility and recurrent pregnancy loss diagnosis.

Endometriosis, infertility, or recurrent pregnancy loss (RPL) are entities characterised by a decrease in Lactobacillus spp. and an increase in bacterial vaginosis-associated bacteria, (BVAV) according with 16S rRNA sequencing studies. However, the use of nucleic acid amplification tests (NAAT) as a tool for diagnosis algorithms is unknown. Seventy-four patients were included, with a median age of 36.5 years old (IQR: 34-39) including infertility (n=31), endometriosis (n=25), or RPL (n=18), for culturing and NAAT using the Allplex™ Bacterial Vaginosis Plus (ABVP) assay (SeegeneⓇ) with endometrial samples. The objective was determining the utility of ABVP assay for diagnosing the entities. Forty-six microorganisms were isolated from 31 out of 74 patients (41.9 %). Twenty-five endometrial samples (33.8 %) were positive for some targets included in the ABVP-assay, with median Ct value ∼37 (IQR: 31.3-37.1) and Qt value 1.43 Log10copies/reaction (IQR:1.1-2.6). For Lactobacillus species, sensitivity and specificity were 80 % and 84 %, respectively. Gardnerella vaginalis, 63.6 % and 95.7 %. No significant increase in BVAV was detected in any of the gynaecological entities. The ABVP and culture based algorithm did not show utility as a tool for endometriosis, infertility, or RPL diagnosis.

Cell-Free DNA Analysis of Fetal Aneuploidies in Early Pregnancy Loss.

Background: Products of conception samples are often collected and analyzed to try to determine the cause of an early pregnancy loss. However, sample collection may not always be possible, and maternal cell contamination and culture failure can affect the analysis. Cell-free DNA-based analysis of a blood sample could be used as an alternative method in early pregnancy loss cases to detect if aneuploidies were present in the fetus. Methods: In this prospective study, blood samples from early pregnancy loss patients were analyzed for the presence of fetal aneuploidies using a modified version of a noninvasive prenatal testing assay for cell-free DNA analysis. Results from cell-free DNA analysis were compared against the gold standard, microarray analysis of products of conception samples. This study was registered with ClinicalTrials.gov, identifier: NCT04935138. Results: Of the 76 patient samples included in the final study cohort, 11 were excluded from performance calculations. The 65 patient samples included in the final analysis included 49 with an abnormal microarray result and 16 with a normal microarray result. Based on results from these 65 samples, the study found that genome-wide cell-free DNA analysis had a sensitivity of 73.5% with a specificity of 100% for the detection of fetal aneuploidies in early pregnancy loss cases. Conclusions: This prospective study provides further support for the utility of cell-free DNA analysis in detecting fetal aneuploidies in early pregnancy loss cases. This approach could allow for a noninvasive method of investigating the etiology of miscarriages to be made available clinically.

X centromeric drive may explain the prevalence of polycystic ovary syndrome and other conditions: Genomic structure of the human X chromosome pericentromeric region is consistent with meiotic drive associated with PCOS and other conditions.

X chromosome centromeric drive may explain the prevalence of polycystic ovary syndrome and contribute to oocyte aneuploidy, menopause, and other conditions. The mammalian X chromosome may be vulnerable to meiotic drive because of X inactivation in the female germline. The human X pericentromeric region contains genes potentially involved in meiotic mechanisms, including multiple SPIN1 and ZXDC paralogs. This is consistent with a multigenic drive system comprising differential modification of the active and inactive X chromosome centromeres in female primordial germ cells and preferential segregation of the previously inactivated X chromosome centromere to the polar body at meiosis I. The drive mechanism may explain differences in X chromosome regulation in the female germlines of the human and mouse and, based on the functions encoded by the genes in the region, the transmission of X pericentromeric genetic or epigenetic variants to progeny could contribute to preeclampsia, autism, and differences in sexual differentiation.

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.

Effects of high-normal fasting blood glucose on ART outcomes of frozen-thawed single blastocyst transfer in women with normal BMI.

PURPOSE: This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI). METHODS: 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97 mmol/L, 1 mmol/L = 18 mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10 mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes. PRIMARY OUTCOME: live birth rate (LBR). RESULTS: LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07 mmol/L, and 5.01 mmol/L, respectively. CONCLUSIONS: In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes.

High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province.

Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss.

Maternal exposure to heat and its association with miscarriage in rural KwaZulu-Natal, South Africa: A population-based cohort study.

BACKGROUND: We sought to improve the current understanding of how climate change impacts women's reproductive health in sub-Saharan Africa. OBJECTIVES: We investigated the relationship between maternal heat exposure and miscarriage (pregnancy ending before 20 weeks gestation) in a South African setting. DESIGN: Population-based cohort study. METHODS: Our study involved data for pregnancies collected via a health and demographic surveillance system in rural KwaZulu-Natal, South Africa between 2012 and 2016. Data from the South African Weather Service were used to compute maternal exposure to heat during the following time windows for each pregnancy: during the month preceding conception (T1) and during the week preceding the study outcome (either a miscarriage or no miscarriage, T2). Heat exposure was operationalized as a continuous variable and defined as the number of days that a mother was exposed to a mean daily temperature of > 26.6°C (A "hot day," equivalent to a mean daily temperature of > 80°F) during T1 or T2. Binary logistic regression was used to investigate the relationship between maternal heat exposure and miscarriage. RESULTS: A total of 105/3477 pregnancies included in our analysis ended in miscarriage (3.0%). Each additional hot day during T1 was associated with a 26% higher odds of miscarriage (odds ratio: 1.26; 95% confidence interval: 1.15-1.38). No significant associations were observed between maternal heat exposure during T2 and the odds of miscarriage (odds ratio: 0.94, 95% confidence interval: 0.73-1.20). The relationship between maternal heat exposure during T1 and the odds of miscarriage was J-shaped. CONCLUSION: There is a clear relationship between maternal heat exposure during the month preceding conception and miscarriage in our sub-Saharan African setting. Given the lack of feasible strategies to reduce pregnancy loss associated with prevailing high temperatures in sub-Saharan Africa, progressive climate change will likely exacerbate existing challenges for women's reproductive health in this region.

Addition of operative hysteroscopy to vacuum aspiration for the management of early pregnancy loss after in vitro fertilization.

OBJECTIVE: To investigate whether operative hysteroscopy in addition to vacuum aspiration for the management of early pregnancy loss effectively increases the success rate of subsequent frozen embryo transfer. DESIGN: Propensity score-matched cohort study. SUBJECTS: Women with a miscarriage at 5 to 16 gestational weeks during an IVF cycle in Peking University Third Hospital from 2015 to 2022. EXPOSURE: Hysteroscopy plus vacuum aspiration versus conventional vacuum aspiration. MAIN OUTCOME MEASURES: Live birth rate in the subsequent frozen embryo transfer. RESULTS: 347 women who underwent vacuum aspiration plus hysteroscopy and 2,562 women who underwent conventional vacuum aspiration were included in the analysis. After propensity score matching (1:1 ratio), 325 women were included in each group. Compared to women who underwent vacuum aspiration, those who underwent vacuum aspiration plus hysteroscopy were associated with a lower rate of live birth in the propensity-based matched cohort (22% vs 30%, aOR = 0.68 (0.47, 0.97)). Biochemical, clinical and multiple pregnancy rates were not significantly different, as was miscarriage rate. In the overall cohort, 11 women experienced surgery reintervention in the vacuum aspiration group (0.4%), while no one required surgery reintervention in the vacuum aspiration plus hysteroscopy group. CONCLUSION: Women who underwent vacuum aspiration plus hysteroscopy might be associated with lower rates of live birth compared to those who underwent vacuum aspiration. Further studies are necessary to establish this relationship definitively.

From chromosomal aberrations to mutations in individual genes - the significance of genetic studies of chorions after miscarriage in the search for causes of miscarriages.

OBJECTIVE: To determine the frequency of chromosomal aberrations in chorions after a miscarriage. The second was to examine selected euploid chorions using a next-generation sequencing (NGS) panel designed to assess 43 genes associated with pregnancy loss. MATERIALS AND METHODS: The 1244 chorions were tested by targeted quantitative fluorescent PCR (QF-PCR, 827 chorions) and microarray-based comparative genomic hybridization (aCGH, 417 chorions). Then, 9 euploid chorions were examined using a designed NGS panel. RESULTS: Trisomies were the most common chromosomal aberration identified in the spontaneous miscarriage samples. The second chromosomal abnormality in the aCGH group and the third most common in the QF-PCR group was monosomy X. Structural aberrations were the third most common aberration in the samples screened by aCGH (7.7% of chorions). In 19% of 647 couples who submitted chorions for analysis after pregnancy loss, the chromosomal abnormality in the chorion originated from a woman with a balanced chromosomal rearrangement. This discovery was statistically significant compared to patients with normal chorions. Using the designed NGS panel, we identified a potentially pathogenic de novo variant in the F5 gene in two euploid chorions. Additionally, among the patients who experienced miscarriages and were screened using the NGS panel, we identified variants in the MDM, ACE, and NLRP2 genes that could be associated with a predisposition to pregnancy loss. CONCLUSION: Numerical aberrations are the most common cause of miscarriages, but structural chromosomal aberrations also account for a significant proportion of abnormal results. Our findings indicate that couples with structural chromosomal abnormalities in material post-miscarriage are at increased risk of carrying balanced chromosomal abnormalities. Moreover, NGS-based analyses can uncover previously unidentified causes of miscarriages in the chorionic villi.