Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

BACKGROUND: Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. OBJECTIVES: To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. SEARCH METHODS: We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. MAIN RESULTS: We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. AUTHORS' CONCLUSIONS: Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

Compounding stress: A mixed-methods study on the psychological experience of miscarriage amid the COVID-19 pandemic.

BACKGROUND: Experiencing a miscarriage can have profound psychological implications, and the added strain of the COVID-19 pandemic may have compounded these effects. This study aimed to explore the psychological experiences, assess the levels of psychological distress (depression, anxiety, and post-traumatic stress disorder), and examine the relationships of personal significance of miscarriage and perceived stress with psychological distress of women in North Carolina who suffered a miscarriage of a desired pregnancy between March 30, 2020, and February 24, 2021, of the COVID-19 pandemic, at 14 to 31 months after the loss. METHODS: We conducted a cross-sectional mixed-methods study using a convergent parallel design. A total of 71 participants from North Carolina completed the online survey and 18 completed in-depth interviews. The survey assessed demographics, mental health and reproductive history, personal significance of miscarriage, perceived stress, anxiety, depression, and PTSD. Interview questions asked about the psychological experience of the miscarriage and how the COVID-19 pandemic affected them and their experience. RESULTS: Findings indicated moderate to severe levels of depression, anxiety, and PTSD, which persisted 14 to 31 months post-miscarriage. After conducting hierarchical binary logistic regressions, we found that perceived stress and prior trauma increased the odds of depression, perceived stress increased the odds of anxiety, and personal significance and prior trauma increased the odds of PTSD symptoms 14-31 months post-miscarriage. Notably, a subsequent successful childbirth emerged as a protective factor against depression, anxiety, and PTSD. Qualitative findings depicted emotions such as profound isolation, guilt, and grief. Women noted that additional pandemic-specific stressors exacerbated their distress. The categories identified via conventional content analysis fell under five broader thematic groups: mental health disorders, negative emotions/feelings, positive emotions/feelings, thoughts, and other experiences. CONCLUSIONS: Miscarriage during the COVID-19 pandemic intensified and added complexity to the psychological distress experienced by affected women. The study underscores the need for comprehensive mental health screenings, specialized support for vulnerable groups, and the necessity of trauma-informed care. Providers are strongly encouraged to adopt a multifaceted, individualized approach to patient care that is cognizant of the unique stressors introduced by the pandemic.

Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Seroprevalence and molecular detection of brucellosis among Pakistani women with spontaneous abortion.

Background: Human brucellosis is a neglected disease transmitted to humans from animals such as cattle, goats, dogs, and swine. The causative agents are bacteria of the genus Brucella, intracellular pathogens usually confined to the reproductive organs of their animal hosts causing sterility and abortions. The objective of the study was to determine the seroprevalence of brucellosis among women with spontaneous abortions (SAW) and compare this seroprevalence with that of healthy pregnant women (HPW). Methods: The case-control study was designed to determine the seroprevalence and molecular detection of brucellosis in women who suffered from spontaneous abortion and healthy pregnant women of the Haripur District of Pakistan. A total of 770 blood samples (n = 385 for each group) were collected from 9 public and 11 private hospitals in Haripur District from December 2021-March 2023. Data on demographic features, epidemiological variables, and risk factors were collected from each participant by structured questionnaires. Initial screening for brucellosis was performed by Rose Bengal Plate Test followed by qRT-PCR for molecular detection of the genus-specific BCSP-31 gene of Brucella. Results: The study showed that anti-Brucella antibodies were more found in SAW 23.63% (91/385) than in HPW 1.29% (5/385). Brucella specific DNA was amplified in 89.01% (81/91) seropositive samples of SAW. Demographic features and risk factors such as age, urbanicity, socioeconomic status, education, occupation, and animal contact were found significantly associated with brucellosis (p ≤ 0.05). Consumption of unpasteurized raw milk (OR = 18.28, 95%CI: 8.16-40.94) was found highly concomitant with seroprevalence. Conclusion: This study reports the first evidence of involvement of brucellosis in spontaneous abortions in women of Pakistan. The study can be used to develop strategies for risk management during pregnancy, to raise awareness for brucellosis, and develop control programs.

A crisis in the life course? Pregnancy loss impacts fertility desires and intentions.

BACKGROUND: An unintended spontaneous termination of a pregnancy can be a traumatic experience affecting the subsequent life course, but has received little attention in socio-demographic studies on fertility intentions or behavior. The theoretical background of our study draws on considerations from life course research, the Theory of Planned Behavior and the Traits-Desires-Intentions-Behavior framework. OBJECTIVE: This study investigates whether the experience of pregnancy loss changes the fertility desires and intentions of women in their subsequent life course. METHODS: We use 11 waves of the Panel Analysis of Intimate Relationships and Family Dynamics (pairfam) with 5197 women in total, of which 281 women (5.4%) reported a miscarriage. Data have been collected annually in Germany since 2008. We investigate four dependent variables capturing different indicators of the ideational dimension of fertility: Personal ideal number of children, realistic number of (additional) children, intention to have a(nother) child in the next two years and importance of having a(nother) child. We study the intrapersonal changes in these items among women after a pregnancy loss, applying linear fixed effect regression models. Controls include parity, age, partnership status, pregnancy status and the interaction of pregnancy loss with whether the woman already had children before the pregnancy loss. RESULTS: We found that the importance of having a(nother) child and the intention to have a(nother) child in the next two years increase after a pregnancy loss. These patterns can only partially be explained by control variables. By contrast, an effect on the ideal number of children as well as the realistic number of children could not be found. The patterns varied, however, across age and stage in the life course, most importantly between mothers and childless women. CONCLUSIONS: Our results demonstrate that the effect of pregnancy loss on the subsequent life course varies across the indicators used and by duration after the pregnancy loss. Overall, they suggest that specifically the younger women in our sample might perceive pregnancy loss as a temporary crisis in their transition to motherhood, or to having another child, and as an impetus to reinforce their fertility goals, while for older respondents this might mark the end of their fertility career. Against the backdrop of rising ages at childbirth, future research on fertility and reproductive health care should pay more attention to reproductive complications and how affected women can be supported in coping with them.

Increased risk of adverse gestational outcomes in pregnant women with primary Sjögren's syndrome.

OBJECTIVES: This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases. METHODS: A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022. RESULTS: This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival. CONCLUSIONS: Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.

The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

BACKGROUND: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. OBJECTIVE: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. STUDY DESIGN: Retrospective cohort and validation study. METHODS: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. RESULTS: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. CONCLUSIONS: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

Cytochrome c oxidase IV isoform 1 (COX4-1) regulates the proliferation, migration and invasion of trophoblast cells via modulating mitochondrial function.

INTRODUCTION: Spontaneous miscarriage is a common complication of early pregnancy. Previous studies have shown that mitochondrial function plays an important role in establishment of a successful pregnancy. Cytochrome c oxidase subunit 4 isoform 1 (COX4I1), a component of electron transport chain complex Ⅳ, is required for coupling the rate of ATP production to energetic requirements. However, there is very limited research on its role in trophoblast biology and how its dysfunction may contribute to spontaneous miscarriage. METHODS: Placental villi (7-10 weeks gestational age) collected from either induced termination of pregnancy or after spontaneous miscarriage were examined for expression of COX4I1. COX4I1 was knocked down by siRNA transfection of primary isolates of EVT cells. Real-time cell analysis (RTCA) and 5-Ethynyl-2'-deoxyuridine (EdU) were used to detect changes in proliferation ability after COX4I1 knockdown of EVT cells. Migration and invasion indices were determined by RTCA. Mitochondrial morphology was observed via MitoTracker staining. Oxidative phosphorylation, ATP production, and glycolysis in COX4I1-deficient cells and controls were assessed by a cellular energy metabolism analyzer (Seahorse). RESULTS: In placental villous tissue, COX4I1 expression was significantly decreased in the spontaneous miscarriage group. Knockdown of COX4I1 inhibited EVT cell proliferation, increased the migration and invasion ability and mitochondrial fusion of EVT cells. Mitochondrial respiration and glycolysis were impaired in COX4I1-deficient EVT cells. Knockdown of MMP1 could rescue the increased migration and invasion induced by COX4I1 silencing. DISCUSSION: Low expression of COX4I1 leads to mitochondrial dysfunction in EVT, resulting in altered trophoblast function, and ultimately to pregnancy loss.

Environmental BaP/BPDE suppressed trophoblast cell invasion/migration and induced miscarriage by down-regulating lnc-HZ01/MEST/VIM axis.

Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic pollutant, could cause miscarriage. However, the detailed mechanisms are still largely unclear and should be further explored. In this study, we discovered that exposure of trophoblast cells with BPDE could suppressed cell invasion/migration by inhibiting MEST/VIM (Vimentin) pathway. Moreover, BPDE exposure also increased lnc-HZ01 expression level, which further inhibited MEST/VIM pathway and then suppressed invasion/migration. Knockdown of lnc-HZ01 or overexpression of MEST could efficiently rescue invasion/migration of BPDE-exposed Swan 71 cells. Furthermore, lnc-HZ01 was highly expressed and MEST/VIM were lowly expressed in recurrent miscarriage (RM) villous tissues compared with healthy control (HC) group. Finally, we also found that BaP exposure inhibited murine Mest/Vim pathway in placental tissues and induced miscarriage in BaP-exposed mice. Therefore, the regulatory mechanisms were similar in BPDE-exposed human trophoblast cells, RM villous tissues, and placental tissues of BaP-exposed mice with miscarriage, building a bridge to connect BaP/BPDE exposure, invasion/migration, and miscarriage. This study provided novel insights in the toxicological effects and molecular mechanisms of BaP/BPDE-induced miscarriage, which is helpful for better elucidating the toxicological risks of BaP/BPDE on female reproduction.

Adnexal masses and pregnancy: a single-center experience of 9 years.

PURPOSE: This study aims to analyze the experience of a tertiary health center about the management of adnexal masses that have been diagnosed during pregnancy or detected accidentally during cesarean delivery. METHODS: This is a retrospective review of 160 women who underwent concurrent surgery for adnexal mass during cesarean section, 24 women who delivered vaginally and subsequently had surgery due to the prenatal diagnosis of adnexal mass and 10 women who underwent surgery for adnexal mass during pregnancy. Corresponding to the delivery and surgery times, 200 women who had no diagnosis of pregnancy-associated adnexal mass served as controls. RESULTS: The women in the control group and study groups had statistically similar gestational age at delivery, birth weight and preterm delivery (p > 0.05 for all). Miscarriage was significantly more frequent in women undergoing surgery for adnexal mass during pregnancy (p = 0.001). The women who had surgery for adnexal mass during pregnancy, at the time of cesarean section and following delivery were statistically similar with respect to surgery type and histopathological diagnosis (p > 0.05 for both). Malignancy was detected in none of the patients who underwent surgery for adnexal mass during pregnancy. Acute abdomen was the indication for the emergency surgery in six patients (3.5%) who had surgery for adnexal mass during pregnancy. Four patients (2.4%) had surgery for adnexal mass during pregnancy due to the high index of suspicion for malignancy. CONCLUSION: The risk of malignancy was relatively lower in this cohort of adnexal masses detected during pregnancy and cesarean delivery. Surgical management of adnexal masses should be postponed to postpartum period as such management leads to an increased risk of miscarriage. Unless there is a need for emergent surgery or cancer staging, vaginal delivery should be encouraged in women diagnosed with adnexal mass during pregnancy.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Importance: Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. Objective: To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. Design, Setting, and Participants: This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Exposures: Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Main Outcomes and Measures: Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Results: Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. Conclusions and Relevance: The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

Chromosome analysis of 303 pregnancy losses in Mexico.

BACKGROUND: Chromosomal abnormalities are present in 50 to 60% of miscarriages and in 6 to 19% of stillbirths. Although microarrays are preferred for studying chromosomal abnormalities, many hospitals cannot offer this methodology. OBJECTIVE: To present the results of the cytogenetic analysis of 303 products of conception (POC), which included 184 miscarriages, 49 stillbirths and 17 cases of undefined age. MATERIAL AND METHODS: Karyotyping, fluorescence in situ hybridization, short tandem repeats and microarrays were used, depending on the type of loss and available sample. RESULTS: In 29 POCs we found maternal tissue and were eliminated from the analyses. Informative results were obtained in 250 (91.2 %)/274 cases; the karyotyping success rate was 80.7%; that of single nucleotide polymorphism microarrays, 94.5%; and that of fluorescence in situ hybridization and short tandem repeat, 100%. Cytogenetic abnormalities were observed in 57.6% of miscarriages and in 24.5% of stillbirths; 94% of total anomalies were numerical and 6% were submicroscopic. CONCLUSIONS: Karyotyping with simultaneous short tandem repeat study to rule out contamination of maternal cells is effective for studying miscarriages; in stillbirths, microarrays are recommended.

ANTECEDENTES: Las alteraciones cromosómicas están presentes en 50 a 60 % de los abortos espontáneos y en 6 a 19 % de los mortinatos. Aunque se prefieren los microarreglos para estudiarlos, numerosos hospitales no pueden ofrecerlos. OBJETIVO: Presentar los resultados del estudio citogenético de 303 productos de la concepción (POC), 184 se obtuvieron de abortos espontáneos, 49 fueron mortinatos y en 17 no se identificó la de edad gestacional. MATERIAL Y MÉTODOS: Se empleó cariotipo, hibridación in situ con fluorescencia, secuencias cortas repetidas en tándem y microarreglos, según el tipo de pérdida y la muestra disponible. RESULTADOS: En 29 POC se encontró tejido materno, por lo que fueron eliminados de los análisis. En 250 (91.2 %)/274 casos se obtuvieron resultados informativos; la tasa de éxito del cariotipo fue de 80.7 %; la de los microarreglos de SNP, de 94.5 %; y la de la hibridación fluorescente in situ y la repetición corta en tándem, de 100 %. Se observaron anomalías citogenéticas en 57.6 % de los abortos espontáneos y en 24.5 % de los mortinatos; 94 % de las anomalías fueron numéricas y 6 %, submicroscópicas. CONCLUSIONES: El cariotipo en conjunto con el estudio de secuencias cortas repetidas en tándem para descartar contaminación de células maternas es efectivo para estudiar abortos espontáneos; los microarreglos se recomiendan en los mortinatos.

Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation.

A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin ß (ß-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of ß-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.

The change of working alliance and the association to treatment outcome in an internet-based therapy after pregnancy loss.

BACKGROUND: Working alliance is a prominent non-specific factor for treatment outcomes in face-to-face and internet-based interventions. The association between working alliance and therapy outcome appears to be time- and disorder-specific, but less is known about the change of working alliance during the intervention and the impact of working alliance in grief-specific interventions. The present study examines the association between the change of working alliance and treatment outcomes in an internet-based intervention for parents who experienced pregnancy loss. METHODS: 228 participants received a grief intervention based on cognitive behavioral therapy with asynchronous text-based therapist feedback. Prolonged grief and related symptoms of traumatic stress, depression, anxiety, and general psychopathology were assessed with validated instruments before and after the intervention. The change of working alliance was assessed using the short version of the Working Alliance Inventory at mid-treatment (session 4) and the end of the treatment (session 10). RESULTS: Data for N = 146 persons was analyzed. Working alliance in total and all subscales increased significantly from sessions 4 to 10. This change in working alliance correlated significantly with a reduction in prolonged grief. Changes in subscales of working alliance also correlated with symptoms of depression and general psychopathology. Regression analysis showed that a change in working alliance predicted a reduction in prolonged grief but did not predict improvements in other grief-related symptoms. CONCLUSION: The results examine the change of working alliance during an internet-based intervention and the association with treatment outcome. A small impact of change in working alliance on treatment outcome of prolonged grief was confirmed, but not on related symptoms. Further research is needed to assess moderators of the alliance-outcome association to improve internet-based interventions. TRIAL REGISTRATION: Not applicable.

Lived experiences of women with spontaneous abortion at a district hospital, South Africa.

BACKGROUND:  Spontaneous abortions occur in 12.5% of pregnancies and have a significant impact on the well-being of women. Dissatisfaction with health services is well-documented, but no studies have been conducted in district health services of the Western Cape. The aim was to explore the lived experiences of women presenting with spontaneous abortions to the emergency department at Helderberg Hospital. METHODS:  A descriptive phenomenological qualitative study used criterion-based purposive sampling to identify suitable participants. Data were collected through semi-structured individual interviews. Atlas-ti (version 22) software assisted with data analysis using the framework method. RESULTS:  A total of nine participants were interviewed. There were four main themes: a supportive environment, staff attitudes and behaviour, the impact of time, and sharing of information. The comfort, cleanliness and privacy of the environment were important. COVID-19 had also impacted on this. Showing interest, demonstrating empathy and being nonjudgemental were important, as well as the waiting time for definitive treatment and the time needed to assimilate and accept the diagnosis. In addition, the ability to give relevant information, explain the diagnosis and help patients share in decision-making were key issues. CONCLUSION:  This study highlighted the need for a more person-centred approach and managers should focus on changes to organisational culture through training and clinical governance activities. Attention should be paid to the physical environment, availability of patient information materials and sequential coordination of care with primary care services.Contribution: This study identifies issues that can improve person-centredness and women's satisfaction with care for spontaneous abortion.

Pregnancy loss in women with systemic lupus erythematosus: Grounded Theory.

OBJECTIVE: to learn the meanings attributed to pregnancy loss by women with Lupus. METHOD: qualitative research, based on Symbolic Interactionism and Grounded Theory. Data collection took place between January and August 2022 through in-depth interviews. Data analysis went through the stages of initial and focused coding. RESULTS: seventeen women participated. The central phenomenon "The climb to motherhood: falls and overcoming" was constructed, consisting of three categories: "Falling to the ground during the climb: the experience of pregnancy loss"; "Getting up and following the path: new attempts to conceive"; and "Remembering the journey: meanings attributed to pregnancy losses". FINAL CONSIDERATIONS: experiencing pregnancy is, analogously, like climbing a mountain, where obstacles need to be overcome to reach the summit. The experience of pregnancy loss is seen as complex, especially when there is fragility in healthcare and a lack of awareness regarding feelings of loss and grief.

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.