Adverse Reproductive Outcomes Research Articles

Early sexual debut among adolescent girls and young women in Sierra Leone: A multilevel analysis of prevalence and predictors.

Early sexual debut among young women is associated with adverse sexual and reproductive health outcomes, including unintended pregnancies and sexually transmitted infections. Despite its negative impact, there is limited research on this issue in Sierra Leone. This study aims to address this gap by examining the prevalence of early sexual debut and its associated factors among adolescent girls and young women aged 15-24 years in Sierra Leone. Data from the 2019 Sierra Leone Demographic and Health Survey was used for the study. Provincial variations in the proportion of early sexual debut were visualised using a spatial map. A mixed-effect multilevel binary logistic regression analysis was performed to examine the factors associated with early sexual debut. The results were presented as adjusted odds ratios (aOR) with a 95% confidence interval (CI) and intraclass correlation coefficients. The prevalence of early sexual debut was 26.1% [24.3, 28.0]. Adolescent girls and young women aged 20-24 were less likely to engage in early sexual debut [aOR = 0.52; 95% CI: 0.41, 0.65] than those aged 15-19. The odds of early sexual debut was lower among adolescent girls and young women with secondary/higher education [aOR = 0.62; 95% CI: 0.45, 0.85] compared to those with no education. Adolescent girls and young women who used the internet in the last 12 months [aOR = 0.50; 95% CI: 0.34, 0.73] and those who belonged to the Fullah ethnic group [aOR = 0.25; 95% CI: 0.07, 0.85] were less likely to engage in early sexual debut relative to those who did not use the internet and those belonging to the Creole ethnic group respectively. Adolescent girls and young women who intend to use contraceptives [aOR = 0.60; 95% CI: 0.46, 0.77] and those who do not intend to use contraceptives [aOR = 0.65; 95% CI: 0.49, 0.88] were less likely to engage in early sexual debut than those who were using contraceptives.Conversely, adolescent girls and young women who were working [aOR = 1.41; 95% CI: 1.12, 1.77] had higher odds for early sexual debut than those not working. The odds of early sexual debut were higher among adolescent girls and young women who were married/cohabiting [aOR = 1.72; 95% CI: 1.32, 2.22] and previously married [aOR = 3.26; 95% CI: 1.61, 6.56] than those who were never married. Adolescent girls and young women living in the North Western area[aOR = 1.81; 95% CI: 1.05, 3.13] had higher odds for early sexual debut than those living in the Eastern province. Early sexual debut is prevalent among adolescent girls and young women in Sierra Leone. Age, education, internet use, ethnicity, contraceptive use intention, marital status, employment status, and province of residence were the factors associated with early sexual debut. The study underscores the need for policymakers, government, and non-governmental organisations to design and implement comprehensive and multifaceted interventions to promote informed decision-making and reproductive health among adolescent girls and young women in Sierra Leone.

Circadian Regulation of Lipid Metabolism during Pregnancy.

A cluster of metabolic changes occur to provide energy for fetal growth and development during pregnancy. There is a burgeoning body of research highlighting the pivotal role of circadian rhythms in the pathogenesis of metabolic disorders and lipid homeostasis in mammals. Perturbations of the circadian system and lipid metabolism during gestation might be responsible for a variety of adverse reproductive outcomes comprising miscarriage, gestational diabetes mellitus, and preeclampsia. Growing studies have confirmed that resynchronizing circadian rhythms might alleviate metabolic disturbance. However, there is no clear evidence regarding the specific mechanisms by which the diurnal rhythm regulates lipid metabolism during pregnancy. In this review, we summarize previous knowledge on the strong interaction among the circadian clock, lipid metabolism, and pregnancy. Analyzing the circadian clock genes will improve our understanding of how circadian rhythms are implicated in complex lipid metabolic disorders during pregnancy. Exploring the potential of resynchronizing these circadian rhythms to disrupt abnormal lipid metabolism could also result in a breakthrough in reducing adverse pregnancy outcomes.

Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts.

Sustained or chronic inflammation in the placenta can result in placental insufficiency, leading to adverse reproductive outcomes such as pregnancy loss. Branched-chain amino acid transaminase 1 (BCAT1) expresses in the placenta and is involved in the pathological inflammatory response, but its role in recurrent miscarriage (RM) has not been fully investigated. In the present study, we delved into the effects of BCAT1 on trophoblast inflammation induced by lipopolysaccharide (LPS) and a mouse model of pregnancy loss induced by LPS. In vitro, after the HTR-8/SVneo cells were treated with LPS and BCATc inhibitor 2 (a selective BCAT inhibitor), the cell apoptosis was verified by TUNEL assay, and the activity of caspase-3 and caspase-9 was detected. Real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF) were used to determine the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and inflammasomes (NLRP3 and ASC) in LPS-treated trophoblast cells. Western blot analysis was performed to verify the expression of phospho-IκBα (p-IκBα) in cells and NF-κB p65 in the nuclei. IF staining was used to detect the nuclear translocation of NF-κB p65. The DNA binding activity of NF-κB was detected by an electrophoretic mobility shift assay (EMSA). The results demonstrated that inhibition of BCAT1 reduced trophoblast apoptosis, suppressed the release of proinflammatory cytokines, and prevented NLRP3 inflammasome activation in response to LPS. Additionally, BCAT1 inhibition blocked the activation of the NF-κB pathway in trophoblasts. This study highlights the potential therapeutic role of targeting BCAT1 in preventing adverse reproductive outcomes associated with chronic placental inflammation.

Sexual violence against ever-married reproductive-age women in East Africa: further analysis of recent demographic and health surveys

BackgroundSexual violence is a violation of women’s rights, resulting in significant physical and psychological challenges and adverse reproductive health outcomes. Addressing these issues demands urgent public health interventions and support systems to mitigate the profound impact on individuals and societies. Thus, this study aimed to assess sexual violence against ever-married reproductive-age women in East Africa.MethodsData retrieved from the recent Demographic and Health Survey (DHS) of East African countries was used, and a weighted sample of 40,740 ever-married reproductive-age women was included. To identify factors associated with sexual violence, multilevel mixed-effects models utilizing robust Poisson regression were applied. Akaike’s and Bayesian information criteria, as well as deviance, were utilized to compare the models. In the multivariable regression model, adjusted prevalence ratios (APR) with 95% confidence intervals (CI) were used to estimate the strength of association, with statistical significance set at a p-value < 0.05.ResultThe pooled proportion of sexual violence among ever-married reproductive-age women in East Africa was 13.05% (95% CI: 12.74–13.36). The multivariable multilevel robust Poisson regression revealed that age at first cohabitation/marriage, having a primary educational level, being employed, residing in a female-headed household, having a husband/partner who drinks alcohol, and living in rural areas were positively associated with sexual violence. On the contrary, having secondary and higher educational levels and living in communities with a high proportion of uneducated women were negatively associated with sexual violence.ConclusionEmpowering girls and women through education reduces their vulnerability. Effective programs should prioritize workplace safety, financial independence, and robust legal protections against harassment and abuse. Raising awareness about the impact of alcohol abuse on relationships and the heightened risk of sexual violence is crucial. Moreover, enhancing access to support services and community networks, especially in rural areas, is essential for preventing and responding to sexual violence.

Cadmium-induced fetal erythropoiesis disturbances in mice

Maternal anemia has been identified as a contributing factor to adverse reproductive outcomes associated with cadmium (Cd) exposure, a common heavy metal. Our recent findings suggest that inhibited erythroid differentiation and enucleation also play significant roles in the direct embryonic toxicity resulting from maternal Cd exposure. However, the effects of Cd exposure on lipid metabolism remodeling, which is essential for physiological erythropoiesis, remain poorly understood. In the present study, pregnant mice were administered low doses of CdCl2 via oral exposure from early to late gestation to mitigate Cd-induced maternal anemia. Compared to vehicle-treated controls, embryos from Cd-treated mice exhibited a slight decrease in weight, though without signs of atrophy. Consistent with our previous observations, fetal livers from Cd-exposed embryos demonstrated a dose-dependent inhibition of erythroid differentiation, as confirmed by ex vivo analysis. Notably, an intrinsic decrease in lipid peroxidation during erythroid differentiation was observed in the bone marrow and fetal livers of vehicle-treated mice, attributed to diminished lipid content. In contrast, this decrease in lipid peroxidation was absent in fetal liver erythroblasts from Cd-treated mice, where an increase in lipid peroxidation was instead noted. These findings elucidate a potential mechanism, lipid peroxidation, underlying Cd-induced embryonic toxicity.

Perspective in the Mechanisms for Repairing Sperm DNA Damage.

DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.

Sexual and reproductive health service utilization and associated factors among youth workers at Kombolcha Industry Park, Kombolcha town, Northeast Ethiopia, 2023.

Youth is a decisive age that shapes the direction of their life and that of their family. However, due to the host of biological, social, and economic factors, youth Industry Park workers can be at high risk of adverse sexual and reproductive health outcomes. Therefore, assessing youth sexual and reproductive health service utilization and associated factors among youth workers is very crucial for timely intervention to their gaps. This study aimed to assess sexual and reproductive health service utilization and associated factors among youth workers working at Kombolcha Industry Park Kombolcha, Northeast Ethiopia, 2023. An institutional-based cross-sectional study was conducted at Kombolcha Industry Park, Kombolcha, among a total of 422 youth workers from 1 January to 30 January 2023. A simple random sampling technique was used to access a total of 422 youth workers in Kombolcha Industry Park. The data were collected using pre-test, structured, and interviewer-administered questionnaires. Data were entered into Epi Data version 3.1 and were exported to SPSS version 26 for analysis. Bi-variable and multivariable binary logistic regression analyses were performed. Adjusted odds ratio with 95% confidence interval was estimated to measure the strength of the association. The level of statistical significance was declared at a p value of less than 0.05. Overall utilization of reproductive health services was 45.50%. Being married [adjusted odds ratio (AOR) = 5.76, 95% CI (2.94, 11.25)], near distance of sexual and reproductive health (SRH) facility to home [AOR = 2.57, 95% CI (1.60, 4.14)], having good knowledge [AOR = 9.23 95%CI (4.88, 17.44)], and good attitude about SRH [AOR = 2.06 95% CI (1.29, 3.28)] were significantly associated with youth SRHs utilization. Youth sexual and reproductive health service utilization among youth workers of Kombolcha Industry Park was low. Ensuring SRHs availability and accessibility, empowering youth with knowledge of SRHs, and advocating sexual and reproductive health services to develop a good attitude might be important in improving reproductive health service utilization. Future researchers should address segments of the population other than Kombolcha Industry Park.

New evidence on adolescent sexual and reproductive health and rights from the West and Central African region.

The African Journal of Reproductive Health is pleased to publish these compendiums of original research in this special edition that document new findings in adolescent sexual and reproductive health and rights from the West and Central African region (WCA). While sub-Saharan Africa has some of the worst indicators of sexual and reproductive health and rights (SRHR) in the world, the indicators are more daunting in the WCA region. To date, the WCA is recognized to have the highest rates of unwanted pregnancy, unsafe abortion, and human immunodeficiency virus (HIV) and other sexually transmissible infections, as well as the lowest contraceptive prevalence rates among adolescents worldwide.1 Despite the high rate of adverse adolescent reproductive health outcomes in WCA, there has been limited documentations of the socio-cultural and economic circumstances that perpetuate these adverse consequences. There have also been no purposefully designed interventions that provide strong scientific evidence for developing strategies to reverse the trend.

Association between exposure to perfluoroalkyl substances (PFAS) and endometriosis in the ENDEA case-control study

BackgroundPerfluoroalkyl substances (PFAS) are environmental contaminants present in a wide range of consumer products and frequently detected in drinking water. They have been linked to adverse reproductive health outcomes in women, but there is limited human evidence on the association of PFAS exposure with endometriosis. Objective/AimTo explore the association between plasma concentrations of several PFAS, considered individually and as a mixture, and the risk of endometriosis in women of childbearing age. MethodsBetween 2018 and 2020, 42 patients with endometriosis and 90 controls undergoing abdominal surgery were recruited at two public hospitals in Granada, Spain. The presence or absence of endometriosis was ascertained by laparoscopic inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Concentrations of 10 PFAS were quantified in plasma samples from participants. Unconditional logistic regression was employed to examine associations of individual PFAS and summed concentrations of short (∑SC) and long-chain (∑LC) PFAS with odds of endometriosis, and quantile g-computation was used to assess their mixture effect. ResultsIn models adjusted for age, schooling, and parity, perfluorotridecanoic acid (PFTrDA) was associated with higher odds of endometriosis (odds ratio [OR] = 1.74; 95 % CI = 1.11–2.73 per 2-fold increase in plasma concentrations), while marginally significant associations were found for perfluorohexane sulfonate (PFHxS) (OR = 1.45, 95 % CI = 0.94–2.21) and ∑SC PFAS (OR = 1.48; 95 % CI = 0.96–2.30). No associations were found for the remaining PFAS. The PFAS mixture was non-significantly associated with 1.7-fold higher odds of endometriosis (95 % CI = 0.73–3.80), with perfluorononanoic acid (PFNA), PFHxS, and PFTrDA being the major contributors to this effect. ConclusionsThese findings suggest that exposure to certain PFAS may increase the odds of endometriosis. However, given the modest sample size, further studies are warranted to verify these results.

Association between semen microbiome disorder and sperm DNA damage.

DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of Lactobacillus species was altered: Lactobacillus iners was enriched in HDFI patients, shedding light on the potential influence of L. iners on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.IMPORTANCEThe DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular, Lactobacillus iners was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.

Impact of a 12-Week Dietary Intervention on Adipose Tissue Metabolic Markers in Overweight Women of Reproductive Age.

The prevalence of overweight and obesity in women of reproductive age leads to significant health risks, including adverse metabolic and reproductive outcomes. Effective dietary interventions are critical to improving health outcomes in this population. This study investigates the impact of a 12-week diet intervention on metabolic markers of adipose tissue in overweight women of reproductive age, determining whether calorie restriction or low-starch diets are more effective, while also accounting for salivary amylase activity. A total of 67 overweight women of reproductive age were enrolled in a randomized controlled trial (RCT). Participants were divided into high-salivary-amylase (HSA) and low-salivary-amylase (LSA) groups based on baseline salivary amylase activity measured using a spectrophotometric method. Each group was further subdivided into two dietary intervention groups: calorie restriction (CR) and low starch (LS), resulting in four subgroups (HSA-CR, HSA-LS, LSA-CR, LSA-LS), along with a control group (CTR) of normal-weight individuals (no intervention). Participants were assigned to a calorie-restricted diet or a low-starch diet for 12 weeks. Key metabolic markers of adipose tissue, including insulin sensitivity, adipokines, cytokines, and lipid profiles, were measured at baseline (T0), 30 min after consuming starch-containing muesli (T1), and 12 weeks after intervention (T2). Active GLP-1, glucagon, and C-peptide levels were assessed to clarify the hormonal mechanisms underlying the dietary effects. Salivary amylase activity was also measured to examine its role in modulating glucose and GLP-1 responses. Both diet interventions led to significant improvements in metabolic markers of adipose tissue, though different ones. Calorie restriction improved insulin sensitivity by effectively reducing visceral fat mass and enhancing insulin signaling pathways. In contrast, the low-starch diet was linked to a reduction in the coefficient of glucose variation influenced partly by changes in GLP-1 levels. Our findings highlight the importance of personalized diet strategies to optimize metabolic health in this demographic.

Navigating the Microbial Landscape: Understanding Dysbiosis in Human Genital Tracts and Its Impact on Fertility.

Dysbiosis, an imbalance in microbial communities, significantly impacts the health and functionality of the human genital tract, with profound implications for fertility and reproductive health. This review explores the intricate relationship between genital tract microbiota and reproductive outcomes, highlighting the composition and dynamics of these microbial communities in both females and males. In females, the vaginal microbiota, primarily dominated by Lactobacillus species, is essential for maintaining a healthy vaginal environment, preventing infections, and supporting reproductive functions. In males, the genital microbiota influences sperm quality and reproductive health. Dysbiosis in the genital tract, manifesting as bacterial vaginosis, yeast infections, urethritis, or prostatitis, disrupts these microbial communities, leading to adverse reproductive outcomes such as infertility, pregnancy, and increased susceptibility to sexually transmitted infections. This review delves into the mechanisms through which dysbiosis affects fertility, including alterations in vaginal pH, mucosal immunity, inflammation, sperm viability, and motility. It also evaluates diagnostic methods, clinical implications, and management strategies, including probiotics, prebiotics, antibiotics, antifungal treatments, lifestyle interventions, and emerging therapeutic approaches. By understanding the microbial landscape of the genital tract and its impact on fertility, this review aims to inform targeted interventions that restore microbial balance and enhance reproductive health, ultimately improving fertility outcomes and the potential for healthy pregnancies.

Pre-pregnancy shift work’s influence on postpartum weight retention: Body mass index’s role

ABSTRACT Shift work is a prevalent workplace exposure, which increases the possibility of unhealthy behaviours and circadian rhythm disruptions and elevates the risk of metabolic diseases and adverse reproductive outcomes. But its potential of increasing the risk of postpartum weight retention remains uncertain. This study aimed to investigate the association between maternal shift work prior to conception and postpartum weight retention, and to identify modifiable factors during pregnancy for prevention. We analysed data from the Taiwan Birth Cohort Study, a prospective cohort of Taiwanese women who gave birth in 2005. We examined the pre-conceptional shift work status of 13,575 mothers and their body weight before pregnancy, before delivery, six and eighteen months after delivery. We used multivariable linear models to examine associations and effect modifications. Maternal shift work before pregnancy was significantly associated with increased postpartum weight retention at six and eighteen months (β-estimate for six months: 0.19-kilogram, 95% CI: 0.03–0.34; eighteen months: 0.23-kilogram, 95% CI: 0.04–0.40). The association between shift work and weight retention at six months postpartum was stronger among mothers who were overweight or obese before pregnancy than mothers with normal weight. This study showed the impact of shift work on postpartum weight retention and suggested a stronger association among mothers with overweight or obesity before pregnancy.

P-210 A new insight into the effects of systemic lupus erythematosus on oocyte and embryo development and female fertility

Abstract Study question Does SLE affect oocyte and embryo development and female fertility in female patients? Summary answer Patients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. What is known already Systemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. However, it’s currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it’s controversial whether SLE hurts fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE. Study design, size, duration This study retrospectively investigated oocyte and embryo development, ovarian reserve, and clinical outcomes in SLE patients who underwent in vitro fertilization (IVF) treatment from January 2013 to September 2022 at the University Hospital. Participants/materials, setting, methods In this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups. Main results and the role of chance After PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 68.6%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both) Limitations, reasons for caution It’s a retrospective and single-center study, which is relevant to an inevitable risk of bias. Due to its special population selection, the sample size of this study is quite small. Wider implications of the findings This study provides data support to explore further the impact of SLE or other autoimmune diseases on female fertility, and it also calls for more attention to be given to these special patients by reproductive physicians. Comprehensive fertility assessment and individualized fertility guidance are recommended for patients with SLE. Trial registration number TJ-IRB20211280

O-075 Particulate matter (PM2.5 and PM10) exposure prior to oocyte collection is associated with decreased live birth rates in subsequent frozen embryo transfers

Abstract Study question Does exposure to particulate matter air pollution prior to oocyte collection (OPU) or frozen embryo transfer (FET) impact FET live birth rates? Summary answer Increasing PM10 and PM2.5 exposure prior to OPU is associated with decreased odds of live birth in subsequent FET, independent of the conditions at FET. What is known already Ambient air pollution is increasing, and exposure is associated with adverse reproductive health outcomes, including infertility, miscarriage, preterm birth and low birth weight. Animal studies have shown that air pollutants can impair spermatogenesis, oogenesis, ovarian reserve and embryogenesis. These findings are corroborated by human epidemiological studies. The impact of ambient air pollution on IVF outcomes is uncertain. Additionally, whether pollutants exert a greater impact during oocyte development or early pregnancy is uncertain. Therefore, studies of FETs offer an opportunity to delineate different phases of reproduction that may be adversely affected by pollution. Study design, size, duration A retrospective analysis of 3,657 FETs in a single Australian centre from January 2013 – December 2021. All FETs during the study period were included; data were collected from the clinic database. Air pollutant concentrations for each day during the study were obtained from the Governmental monitoring body, including SO2, CO, O3, NO2, PM10 and PM2.5. Evaluation of FETs allowed separation of environmental effects during oocyte development and during early pregnancy. Participants/materials, setting, methods Quartiles were created for pollutants averaged over 24 hours, 2 weeks, 4 weeks and 3 months prior to OPU and prior to FET. Multi-pollutant models were created to account for co-exposures and were adjusted for variables at the time of OPU and FET. Bonferroni correction was made to account for the 4 timepoints tested on each outcome. Linear trends were assessed for each model, and pairwise comparisons against the first quartile were performed. Main results and the role of chance Overall, air quality was excellent, with pollutant levels within published safe limits on &amp;gt; 99% of days during the study period. Increasing PM10 exposure in the 2 weeks prior to OPU was associated with decreased odds of livebirth (linear trend p = 0.009); the odds of livebirth decreased by 38% when PM10 concentrations were in the highest quartile compared with the lowest (OR 0.62, p = 0.010). Increasing PM2.5 exposure in the 3 months prior to OPU was also associated with decreased odds of livebirth (linear trend p = 0.011). No significant linear trends were observed between livebirths and other pollutants. The summer seasonal association with livebirth that we have previously demonstrated consistently held in the multi-pollutant models. No significant linear trends were observed between air pollutants and biochemical pregnancy, clinical pregnancy, miscarriage, gestation at birth or embryological outcomes. Limitations, reasons for caution The retrospective design is a limitation. Whilst corrections were made for multiple pollutant co-exposures, other environmental conditions, patient factors and repeated cycles, we were unable to account for all potential covariates. To reduce the risk of type 1 error due to the multiple timeframes, we utilised a Bonferroni correction. Wider implications of the findings Even when PM2.5 and PM10 exposures are within so-called “safe” ranges, increasing exposure in the weeks and months prior to OPU are associated with decreasing livebirth rates, independent of the conditions at the time of FET. Trial registration number 2022/ET000980

Racial and ethnic disparities in reproductive medicine in the United States: a narrative review of contemporary high-quality evidence

There has been increasing debate around how or if race and ethnicity should be used in medical research-including the conceptualization of race as a biological entity, a social construct, or a proxy for racism. The objectives of this narrative review are to identify and synthesize reported racial and ethnic inequalities in obstetrics and gynecology (ob/gyn) and develop informed recommendations for racial and ethnic inequity research in ob/gyn. A reproducible search of the eight highest impact ob/gyn journals was conducted. Articles published between January 1, 2010, and June 30, 2023 containing keywords related to racial and ethnic disparities, bias, prejudice, inequalities, and inequities were included (n=318). Data were abstracted and summarized into four themes: 1) access to care, 2) adherence to national guidelines, 3) clinical outcomes, and 4) clinical trial diversity. Research related to each theme was organized topically under the headings i) obstetrics, ii) reproductive medicine, iii) gynecologic cancer, and iv) other. Additionally, interactive tables were developed. These include data on study timeline, population, location, and results for every article. The tables enable readers to filter by journal, publication year, race and ethnicity, and topic. Numerous studies identified adverse reproductive outcomes among racial and ethnic minorities as compared to white patients, that persist despite adjusting for differential access to care, socioeconomic or lifestyle factors, and clinical characteristics. These include higher maternal morbidity and mortality among Black and Hispanic/Latinx patients; reduced success during fertility treatments for Black, Hispanic/Latinx, and Asian patients; and lower survival rates and lower likelihood of receiving guideline concordant care for gynecological cancers for non-white patients. We conclude that many racial and ethnic inequities in ob/gyn cannot be fully attributed to patient characteristics or access to care. Research focused on explaining these disparities based on biological differences incorrectly reinforces the notion of race as a biological trait. More research that deconstructs race and assesses efficacy of interventions to reduce these disparities is needed.

Vaginal fungi are associated with treatment-induced shifts in the vaginal microbiota and with a distinct genital immune profile.

Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted by both human and bacterial cells. Human and bacterial EVs (BEVs) propagate and transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues by bacterial cells is not required for immunogenic stimulation. This phenomenon is important in the feto-maternal interface, where optimum tolerance between the mother and fetus is required for a successful pregnancy. Though the intrauterine cavity is widely considered sterile, BEVs from diverse sources have been identified in the placenta and amniotic cavity. These BEVs can be internalized by human cells, which may help them evade host immune surveillance. Though it appears logical, whether bacterial cells internalize human EVs or human EV cargo is yet to be determined. However, the presence of BEVs in placental tissues or amniotic cavity is believed to trigger a low-grade immune response that primes the fetal immune system for ex-utero survival, but is insufficient to disrupt the progression of pregnancy or cause immune intolerance required for adverse pregnancy events. Nevertheless, the exchange of bioactive cargos between human and BEVs, and the mechanical underpinnings and health implications of such interactions, especially during pregnancy, are still understudied. Therefore, while focusing on the feto-maternal interface, we discussed how human cells take up BEVs and whether bacterial cells take up human EVs or their cargo, the exchange of cargos between human and BEVs, host cell (feto-maternal) inflammatory responses to BEV immunogenic stimulation, and associations of these interactions with fetal immune priming and adverse reproductive outcomes such as preeclampsia and preterm birth.

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose–response meta-analysis

BackgroundTo inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. MethodsWe conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults’ preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers’ data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose–response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. ResultsWe identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces).General public studies.From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97–1.34, 95% prediction interval (PI): 0.83–1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96–1.36, 95% PI: 0.84–1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02–1.24, 95% PI: 0.99–1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth.Occupational studies.In occupational studies, based on dose–response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94–1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DiscussionMost of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes.Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

Reproductive toxicology of environmental endocrine-disrupting chemicals in women: a cohort study protocol.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. Discussion: All of these results reveal EDCs may disrupt female reproduction.