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Study Objective: The association between endometriosis and congenital uterine anomalies (CUAs) has been discussed for decades, but existing evidence about this association is scarce. The aim of our study is to evaluate the prevalence of CUAs in women with endometriosis and to identify specific characteristics in women with both CUAs and endometriosis in a large cohort of patients., Design: This is a retrospective single-center observational study conducted between January 2006 and June 2021., Setting: Swiss tertiary hospital PATIENTS: Women with histologically confirmed endometriosis at laparoscopy., Interventions: All women included in this study underwent a preoperative 2D ultrasound by an experienced sonographer. In cases of suspected intrauterine pathology, bleeding disorders, or infertility, an additional hysteroscopy was performed., Measurements and Main Results: Out of 1566 women with histologically confirmed endometriosis, 93 were diagnosed with CUAs (5.9%). The most frequent malformations were U1c (arcuate uterus) (41/93, 44.1%), U2a (partial septate uterus) (19/93, 20.4%), U3b (complete bicorporeal uterus) (17/93, 18.3%) and U3a (partial bicorporeal uterus) (10/93, 10.8%). Women with both CUAs and endometriosis were more frequently diagnosed with endometriosis rASRM stage IV (p=0.017) and presence of dysmenorrhea (p=0.019) in comparison to women with endometriosis and a morphologically normal uterus., Conclusions: To the best of our knowledge, this is the largest endometriosis population examined for the prevalence of CUAs. According to our findings, the prevalence of CUAs in women with endometriosis does not appear to be higher than in the general population. However, women with CUAs and endometriosis are more likely to suffer from severe endometriosis (rASRM stage IV) and dysmenorrhea compared to endometriosis patients without CUA., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest, (Copyright © 2025. Published by Elsevier Inc.)

Objective: This study aims to evaluate the reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss (RPL) combined with intrauterine adhesions (IUA)., Design: Single-center retrospective cohort study., Setting: International referral hospital for women with IUA and RPL., Patients: Between January 2018 and June 2022, a cohort of 64 women diagnosed with RPL and IUA were studied, with a follow-up period of at least one year after hysteroscopic adhesiolysis., Interventions: All patients had a diagnosis of IUA from the diagnostic hysteroscopy and were treated with hysteroscopic adhesiolysis, utilizing intraoperative ultrasound monitoring as required., Main Measurements: Live birth rate and menstrual pattern change (subjective assessment) after hysteroscopic adhesiolysis., Results: In our cohort, 59.38% (38/64) achieved pregnancy following hysteroscopic adhesiolysis, with 92.11% (35/38) conceiving within two years of the procedure. The miscarriage rate was recorded at 17.19% (11/64), and the live birth rate stood at 42.19% (27/64). Throughout the extended follow-up period, 64.06% (41/64) of the patients reported increased menstrual blood volume and improvements in menstrual patterns posthysteroscopic adhesiolysis. Univariate analysis indicated that being aged ≥35 years (p = .026), having a history of infertility (p = .003), the presence of moderate or severe IUA (p = .023), and experiencing menstrual improvements postsurgery (p = .001) were independent predictors of live birth. Multivariate analysis further identified that women with a history of infertility had a reduced chance of live birth following hysteroscopic adhesiolysis (p = .008), while those who reported menstrual pattern improvements postoperatively had an increased probability of achieving a live birth (p = .031)., Conclusions: Our findings indicate that RPL and IUA patients without prior infertility and showing menstrual pattern improvement after hysteroscopic adhesiolysis, are more likely to achieve live births. Standardized hysteroscopic treatment, postoperative anti-adhesion care, and early pregnancy planning are key to improving fertility outcomes in these patients., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate prophylactic uterotonics, antifibrinolytic medications, and vasoconstrictive agents in the prevention of hemorrhage during second-trimester abortions., Data Sources: PubMed, Embase (Elsevier platform), Evidence-Based Medicine Reviews (Ovid platform), and Web of Science were searched from database creation to October 30, 2023., Study Eligibility Criteria: Randomized controlled trials, cohort studies, case-control studies, and case series evaluating pregnant individuals (between 13 0/7 and 27 6/7 weeks of gestation) who underwent dilation and evacuation and received prophylactic uterotonics (methylergonovine, carboprost, oxytocin, or misoprostol), antifibrinolytic medications (tranexamic acid), or vasoconstrictive agents (vasopressin, lidocaine with epinephrine) were included in the study. The outcomes of interest included postprocedural bleeding, rate of medications to treat bleeding, blood transfusion, reoperation, and transfer to a higher level of care for hemorrhage., Methods: Of note, 2 authors independently screened the abstracts using the Systematic Review Data Repository. A third reviewer resolved discrepancies. The full text of accepted abstracts was retrieved and assessed for eligibility by 2 independent authors. Eligible studies were independently assessed for quality and bias by 3 authors. A consensus review resolved discrepancies., Results: Among 5834 abstracts screened, 11 studies met the inclusion criteria: 5 randomized controlled trials, 3 retrospective cohort studies, and 3 case series, totaling 3857 individuals. The paucity of studies combined with the heterogeneity of included trials precluded the performance of the meta-analysis. Of note, 4 studies evaluating misoprostol were of overall low-quality evidence and primarily assessed misoprostol's use for cervical dilation. Thus, its efficacy in bleeding prophylaxis remains unclear. Moreover, 2 high-quality trials evaluating oxytocin concluded that oxytocin use resulted in decreased blood loss, without a difference in interventions to control bleeding. Furthermore, 2 studies provided moderate-quality evidence that paracervical vasopressin use decreased blood loss, particularly at advanced gestational ages, but subsequent intervention outcomes were not assessed. High-quality evidence evaluating methylergonovine found that this medication increased blood loss at the time of the procedure., Conclusion: Current evidence on hemorrhage prophylaxis at the time of dilation and evacuation supports the use of intravenous oxytocin or paracervical vasopressin to decrease procedural blood loss, without an associated decrease in transfusion rate or use of other interventions. Future research on outcomes by gestational age can identify subgroups with the potential to derive the most benefit., (Published by Elsevier Inc.)

Maternal exposure to per- and polyfluoroalkyl substances (PFASs) has been linked to adverse pregnancy outcomes (APOs). Nonetheless, the genetic causality underlying this association remains unknown. This research employed a bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal associations between PFASs exposure and APOs risk. PFASs data were sourced from the GWAS Catalog, and APOs data were retrieved from the FinnGen consortium. Causal estimation primarily employed inverse variance weighting, with Cochran's Q test for instrumental variable heterogeneity, and MR-Egger, MR-PRESSO, and leave-one-out tests for sensitivity analyses. The possibility of reverse causality was investigated through reverse MR. MR evidence revealed a notable correlation between perfluorooctanoic acid (PFOA) and abruptio placentae (OR=1.498, P=0.026), as well as short gestation and low birth weight (OR=1.720, P=0.013). Exposure to perfluorooctanesulfonic acid (PFOS) increased the risk of preeclampsia or eclampsia (OR=1.128, P=0.030) and gestational hypertension (OR=1.076, P=0.049), but decreased the risk of premature rupture of membranes (OR=0.916, P=0.033). The results obtained were consistent across various sensitivity analyses. Reverse MR results was negative. These findings may provide a reference for prevention strategies and intervention measures for PFASs exposure and APOs, and provide a framework for studying the causal effects of environmental pollutant exposure and human diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22-1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Cervical cytology remains a critical screening tool for cervical cancer. While various factors can influence cytology quality, the effect of lubricant type used during specimen collection has been previously studied with inconclusive results. This study aimed to evaluate the impact of surgical lubricant on cervical cytology results and elucidate risk factors associated with unsatisfactory results. We hypothesized that switching from a carbomer-containing lubricant to a noncarbomer, water-soluble lubricant would improve specimen adequacy in cervical cytology., Materials and Methods: A retrospective chart review was performed examining patient cytologic results from January to December 2017 at a single academic institution. After historical rates of unsatisfactory cytology were higher than acceptable standards, the practice changed lubricant formulation from a carbomer containing lubricant to a noncarbomer, water soluble lubricant. Demographic data and treatment characteristics were collected for eligible patients. Matched analysis was performed to examine factors associated with an unsatisfactory cytology result., Results: After the change in lubricant, there was a significant decline in the rates of unsatisfactory cytology from 9.6% to 5.7%, P = 0.01. This decline was also observed when patients were matched based on menopausal status, personal history of gynecologic malignancy, pregnancy status, and cytology specimen type (10.0% to 4.8%, P = 0.001)., Conclusions: Change in lubricant from a carbomer containing to noncarbomer, water soluble product was associated with a statistically significant decline in the rates of unsatisfactory cytology. Although prior data have had mixed results as to the etiology of unsatisfactory cytology, we feel that this directly contributed to the high rates observed at our institution., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Stress urinary incontinence (SUI) is a common disease that seriously affects the quality of life of patients. In recent years, studies have shown that apolipoprotein E (ApoE) plays a role in neuroprotection and repair, but its specific role in SUI remains unclear. The aim of this study was to investigate the effect of macromolecular protein ApoE related markers on the prognosis of rats with SUI treated by modified Buzhong Yiqi Decoction (MBZYQD), in order to provide a new target for the treatment of SUI. Healthy rats were selected to establish a SUI model and divided into groups. The levels of ApoE related metabolites in blood of rats were detected by Metabolomics analysis and Lipidomics analysis. The urine leakage point pressure (LPP) were compared in each group, and the therapeutic effect of MBZYQD was evaluated. Compared with the model group, the LPP of rats in MBZYQD supplemented group was significantly higher. Compared with the control group, the LPP of MBZYQD was not statistically significant before and after treatment. The macromolecular protein ApoE may plays a key role in the treatment of SUI by MBZYQD, which can improve symptoms by regulating lipid metabolism repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Research Question: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring?, Design: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors., Results: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544)., Conclusion: This study suggests that children born through FET have increased risk of developing food allergy in early childhood., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: We analyze the characteristics and related factors of human chorionic gonadotropin (hCG) of pituitary origin to establish the reference interval to resolve clinical confusion and avoid harmful therapy to Chinese postmenopausal women with "positive" hCG., Materials and Methods: This retrospective cohort study identified individuals who underwent hCG measurements at an academic hospital. Three gonadotropins (hCG, follicle stimulating hormone (FSH), and luteinizing hormone (LH)) was drawn from medical records. The age-stratified analyses were performed first. Then the correlations of hCG and FSH, LH as well as age were analysed. Finally, characteristics and associations of hCG, LH, and FSH were evaluated to identify pituitary hCG in postmenopausal women in clinical settings., Results: In total, 9796 cases from 11172 records met inclusion criteria and contributed 9796 hCG, 7541 FSH, and 7536 LH values. The upper reference interval for our cohorts was 5.3 IU/L. HCG, FSH, and LH concentration had no significant correlations with age. HCG moderately correlated with FSH (r = 0.47) and LH level (r = 0.53). However, it was FSH but not LH that manifested good clinical applicability., Conclusion: The prevalence of hCG≥5.0 IU/L and 5.3 IU/L in women ≥55 years is 2.8% and 2.3% in the study population from China. The level of hCG 5.3 IU/L was suggested to be the positive threshold for postmenopausal women. FSH≥40IU/L helps to distinguish the pituitary source of hCG in postmenopausal women whose serum hCG concentrations were between 5.3 and 16 IU/L., Competing Interests: Conflicts of interest None reported., (Copyright © 2024. Published by Elsevier B.V.)

Research Question: To what extent do legislative measures impact standard reproductive outcome parameters?, Design: Retrospective cohort study using data from the Swiss national IVF registry analysing the outcomes of 13,908 women undergoing embryo transfers resulting from their first lifetime oocyte retrieval before (2014-2016) or after (2020-2022) revision of the legislation, allowing extended culture for 12 zygotes. Live birth rates (LBR) and cumulative LBR (cLBR) were compared in fresh and frozen embryo transfer strategies in both periods. Adjusted multivariable mixed model analyses were performed to determine OR and incidence rate ratios (IRR)., Results: Before revision of the legislation, LBR was higher for fresh embryo transfers compared with frozen embryo transfers (27.2% versus 22.7%; P = 0.006). After revision of the legislation, LBR was lower for fresh embryo transfers (29.3% versus 36.3%; P < 0.001), and cLBR was higher for the freeze-all embryo transfer strategy (59.0% versus 39.8%; P < 0.001). However, in a multivariable analysis, no difference in the odds of live birth was found between fresh and frozen embryo transfers (OR = 1.08, 95% CI 0.95-1.22), and the freeze-all embryo transfer strategy was not found to be more effective than the fresh embryo transfer strategy (IRR = 1.12, 95% CI 0.98-1.27). In a subgroup analysis, fresh blastocyst embryo transfers showed higher LBR than cleavage stage embryo transfers (OR = 2.01, 95% CI 1.62-2.49)., Conclusion: The change in national legislation provided the unique opportunity to evaluate the legal impact on reproductive outcomes. Besides a reduction in the number of multiple births, LBR in frozen embryo transfers improved, resulting in comparable success of fresh and frozen embryo transfer strategies. In addition to technological improvement, the legal framework influences the evolution of clinical practice, thereby contributing to enhanced reproductive outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester., Methods: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses., Results: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted β=0.026, 95 % CI: 0.003-0.050)., Conclusion: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester., Competing Interests: Declaration of Competing Interest The authors of this article declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy., Objective: To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes., Study Design: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes., Results: Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group., Conclusion: This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Syncytins are endogenous retroviral envelope proteins which induce the fusion of membranes. A human representative of this group, endogenous retrovirus group W member 1 envelope (ERVW-1) or syncytin-1 is present in trophoblast-derived extracellular vesicles and supports the incorporation of these extracellular vesicles into recipient cells. During pregnancy, placenta-derived extracellular vesicles participate in feto-maternal communication. Bovine fetal binucleate trophoblast cells express the syncytin, bovine endogenous retroviral envelope protein K1 (BERV-K1). These cells release extracellular vesicles into the maternal stroma, but it is unclear whether BERV-K1 is included in these extracellular vesicles. Here, extracellular vesicles were isolated from bovine placental tissue using collagenase digestion, ultracentrifugation, and size exclusion chromatography. They were characterized with transmission electron microscopy, nanoparticle tracking analysis, immunoblotting and mass spectrometry. Immunohistochemistry and immunoelectron microscopy were used to localize BERV-K1 within the bovine placental tissue. The isolated extracellular vesicles range between 50 and 300 nm, carrying multiple extracellular vesicle biomarkers. Proteomic analysis and immunoelectron microscopy confirmed BERV-K1 presence on the isolated extracellular vesicles. Further, BERV-K1 was localized on intraluminal vesicles in secretory granules of binucleate trophoblast cells. The presence of BERV-K1 on bovine placental extracellular vesicles suggests their role in feto-maternal communication and potential involvement of BERV-K1 in uptake of extracellular vesicles by target cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal interests influencing the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. And several gene loci and transporter proteins that associated with uric acid transport functions have been identified. Retinol Dehydrogenase 12 (RDH12), recognized for its role in safeguarding photoreceptors, and our study investigated the potential impact of Rdh12 mutations on other organs and diseases, particularly hyperuricemia. We assessed Rdh12 mRNA expression levels in various tissues and conducted serum biochemical analyses in Rdh12 -/- mice. Compared with the wild type, significant alterations in serum uric acid levels and kidney-related biochemical indicators have been revealed. Then further analysis, including quantitative RT-PCR of gene expression in the liver and kidney, highlighted variations in the expression levels of specific genes linked to hyperuricemia. And renal histology assessment exposed mild pathological lesions in the kidneys of Rdh12 -/- mice. In summary, our study suggests that Rdh12 mutations impact not only retinal function but also contribute to hyperuricemia and renal disease phenotypes in mice. Our finding implies that individuals with Rdh12 mutations may be prone to hyperuricemia and gout, emphasizing the significance of preventive measures and regular examinations in daily life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

It has been reported that N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), a derivative of the tire antioxidant, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), exhibits acute toxicity towards organisms. However, the possible reproductive toxicity of 6PPD-Q in mammals has rarely been reported. In this study, the effects of 6PPD-Q on the reproductive toxicity of C57Bl/6 male mice were assessed after exposure to 6PPD-Q for 40 days at 4 mg/kg body weight (bw). Exposure to 6PPD-Q not only led to a decrease in testosterone levels but also adversely affected semen quality and in vitro fertilization (IVF) outcomes, thereby indicating impaired male fertility resulting from 6PPD-Q exposure. Additionally, transcriptomic and metabolomic analyses revealed that 6PPD-Q elicited differential expression of genes and metabolites primarily enriched in spermatogenesis, apoptosis, arginine biosynthesis, and sphingolipid metabolism in the testes of mice. In conclusion, our study reveals the toxicity of 6PPD-Q on the reproductive capacity concerning baseline endocrine disorders, sperm quality, germ cell apoptosis, and the sphingolipid signaling pathway in mice. These findings contribute to an enhanced understanding of the health hazards posed by 6PPD-Q to mammals, thereby facilitating the development of more robust safety regulations governing the utilization and disposal of rubber products., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals known for their adverse effects on humans. Growing concern has risen regarding the reproductive toxicity of PFAS, but whether PFAS affect endometriosis remains to be explored. This hospital-based case-control study included 240 laparoscopic-confirmed endometriosis cases and 334 normal controls in China from 2014 to 2018. Concentrations of thirty-three legacy and emerging PFAS were measured in the plasma samples. Associations between single PFAS and endometriosis were estimated by binary logistic regression. The elastic net regression (ENR) model was used to identify dominant PFAS related to endometriosis. The joint effect of the PFAS mixture on endometriosis was assessed by principal component analysis (PCA), Bayesian kernel machine regression (BKMR), and quantile-based g-computation (q-gcomp). In the single-PFAS model, significant positive associations of PFOA [adjusted odds ratio (95 % CI): 1.22 (1.00, 1.51)], total PFOS [1.19 (1.05, 1.34)] and two branched PFOS isomers [1.16 (1.09, 1.22) for 1m-PFOS; 1.18 (1.04, 1.34) for 6m-PFOS] with increased endometriosis odds were observed. Mixture models showed that the joint effect of PFAS mixture on endometriosis was significant [1.24 (1.05, 1.48)], mainly driven by 1m-PFOS. The PFOS isomers profile suggested a PFOS precursor biotransformation source of 1m-PFOS in our population. Our study suggests that branched isomers of PFOS may be associated with endometriosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Follicle dysplasia can cause polycystic ovary syndrome, which can lead to anovulatory infertility. This study explored gene(s) that may contribute to polycystic ovary syndrome., Methods: Three animal models of polycystic ovary syndrome were created by treating 3-week-old rats respectively with estradiol valerate, testosterone propionate, or constant illumination for 8 weeks. Granulosa cells from the three disease groups and from healthy controls were transcriptionally profiled to identify differentially expressed genes. The phosphodiesterase-4d (Pde4d) was screened as the most promising candidate pathogenic gene. The Pde4d was overexpressed in rats via intrabursal infection with recombinant lentivirus to see the effect of Pde4d on ovarian morphology. The potential roles of the candidate gene and interactors of the encoded protein were explored using polymerase chain reaction, western blotting, transfection and co-immunoprecipitation., Results: All three rat models of polycystic ovary syndrome showed polycystic ovary phenotype. Seven promising candidate genes were obtained by transcriptomics and verifications. Pde4d was further investigated because it could trigger downstream signaling pathways. The Pde4d overexpression in rat ovary induced cystic follicles. It inhibited follicle maturation through a mechanism involving inhibition of cAMP-PKA-CREB signaling. The Pde4d also inhibited phosphorylation of c-Jun N-terminal kinase to reduce apoptosis in the ovary, through a mechanism involving interaction of its poly-proline domain with the protein POSH., Conclusion: Upregulation of Pde4d may contribute to polycystic ovary syndrome by impeding follicle maturation and preventing apoptotic atresia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshop's objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity. The attendees agreed that environmental obesogens are real, significant, and a contributor at some degree to weight gain at the individual level and to the global obesity and metabolic disease pandemic at a societal level; moreover, it is at least, in theory, remediable., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Doping in elite or amateur athletes with testosterone, androgens and anabolic steroids (A/AS) has as a main objective to develop muscle strength and mass to improve sports performance. Massive doping is a worldwide public health issue insufficiently known by physicians in general and by endocrinologists in particular. Yet, its prevalence, probably underestimated, would be between 1 and 5% at the international level. Numerous deleterious effects associated with A/AS abuse have been identified: inhibition of the gonadotropic axis responsible for hypogonadotropic hypogonadism and infertility in men, and masculinization (defeminization), hirsutism and anovulation in women. Metabolic (very low HDL cholesterol), hematological (polycythemia), psychiatric, cardiovascular and hepatic complications have also been documented. As a result, anti-doping agencies have developed increasingly effective techniques for detecting A/AS, both to identify and punish cheating athletes and to protect the health of the greatest number of them. These techniques use a combination of liquid and gas chromatographic methods coupled with mass spectrometry, known respectively by the acronyms LC-MS and GC-MS. These detection tools have a remarkable sensitivity and specificity to detect natural steroids and synthetic A/AS of known structure. Furthermore, by distinguishing isotopes, it is also possible to distinguish natural endogenous hormones, testosterone and androgenic precursors from those administered for doping purposes. For elite athletes, a "biological passport" has also been introduced. It consists of monitoring the evolution of steroids and their metabolites, as well as other biological parameters in the blood and urine over time after having established a basal state athlete signature, established, a priori, without doping. Better training of health professionals, general practitioners and specialists should be a priority for academic institutions and medical societies. It would provide them with better knowledge of the populations at risk and the clinical and biological semiology of male and female doping, including withdrawal syndrome associated with anxiety and depression following cessation of chronic A/AS use. The ultimate goal is to provide these physicians with the keys to treating these patients while combining medical rigor and empathy. These points will be addressed in this short manuscript., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring., Objective: This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age., Study Design: This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women's Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured the offspring's height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes., Results: A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09-0.90; beta, 0.22; 95% confidence interval, 0.09-0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P=.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P=.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis., Conclusion: At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Infertility affects about 10-15% couples over the world, among which a large number of cases the underlying causes are still unclear. Recent studies suggest that environmental factors may play an important role in these idiopathic infertilities. Arsenic is a heavy metal found in drinking water over the world. Its effect on the development of female reproductive system at the environmental-relevant levels is still largely unknown. To test the hypothesis that arsenic exposure during juvenile and puberty may affect sex maturation and female reproductive system development, SD rats of 3 weeks of age were exposed to arsenic with environmental-relevant levels (0, 0.02, 0.2, or 2 mg/L, n = 16/group) through drinking water for about 44 days until the rats reached adulthood (65 days of age). Arsenic exposure significantly reduced the weights of both ovary and uterus without affecting the body weight. Also, arsenic exposure disturbed estrus cycles and reduced the numbers of primordial follicles and corpora lutea while increased atretic follicles. In addition, arsenic reduced serum levels of estradiol, progesterone and testosterone but increased LH and FSH levels in dose-dependent manners. QPCR and Western blot experiments indicated arsenic selectively down-regulated ovarian steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK-JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, arsenic-exposed dams had smaller pups, reduced litter size and lower number of male pups without a change in female pups. In conclusion, juvenile and pubertal arsenic exposures at environmental-relevant levels significantly reduced reproductive functions and capacity by adult. Since the lowest effective dose is very close to the government safety standards, the relevancy of arsenic over exposure to reproductive defects in human deserves further study., (Copyright © 2022. Published by Elsevier Inc.)

Background: Non-Hispanic Asians (NHA) in USA have been reported with higher arsenic (As), lead (Pb), cadmium (Cd), mercury (Hg) and their specific species levels, comparing with non-NHA. This study aimed to investigate the associations of these metal/metalloid levels with blood pressure levels and prevalence of hypertension among general NHA using the 2011-2018 National Health and Nutrition and Examination Survey (NHANES) data., Methods: The study included participants aged 20 years and older with determinations of As, Dimethylarsinic acid (DMA), Pb, Cd, Hg and methyl-Hg (MeHg) in blood (n = 10, 177) and urine (n = 5, 175). These metals/metalloid levels were measured by inductively coupled plasma mass spectrometry. Systolic (SBP) and diastolic blood pressure (DBP) levels were examined through a standardized protocol. Censored normal regression model and logistic regression model were employed to explore the associations of As, DMA, Pb, Cd, Hg and MeHg levels with blood pressure levels and prevalence of hypertension respectively, and potential confounders were adjusted in these regression models. Quantile-based g-computation approach was used to analysis joint effect of metals mixture on blood pressure level and hypertension., Results: For NHA, urinary As and Hg levels were associated with increased DBP level; Higher blood Hg and MeHg levels were related to increased blood pressure levels and hypertension; However, negative association was observed between urinary Cd and SBP level; Blood metals mixture (including blood Pb, Cd and Hg) was associated with increased DBP level, but not for hypertension. For non-NHA, urinary As and DMA levels were associated with increased SBP level, but not DBP level and prevalence of hypertension; Urinary Pb level was associated with decreased DBP level; Nevertheless, positive associations were observed between blood Pb levels and SBP and prevalence of hypertension; Blood Hg level was associated with decreased DBP level and prevalence of hypertension; Furthermore, blood MeHg level was associated with decreased DBP level; Positive association was observed between blood metals mixture and increased SBP level among non-NHA., Conclusions: Highly exposed to Hg level among NHA was associated with increased blood pressure levels and prevalence of hypertension. Urinary As level was associated with increased DBP level among NHA. Furthermore, blood metals mixture was related to increased DBP level among NHA. Further prospective studies with larger sample size should be performed to warrant the results., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Emerging per- and polyfluoroalkyl substances (PFAS) alternatives are increasingly used in daily life. Although legacy PFAS have been associated with miscarriage in previous studies, it remains unknown whether exposure to emerging and legacy PFAS has any impact on the risk of unexplained recurrent spontaneous abortion (URSA). We conducted a case-control study with 464 URSA cases who had at least 2 unexplained miscarriages and 440 normal controls who had at least one normal livebirth. Concentrations of 21 PFAS in plasma, including three emerging PFAS alternatives, eight linear and branched PFAS isomers, four short-chain PFAS, and six legacy PFAS, were measured by ultra-performance liquid chromatography coupled with a tandem mass spectrometry (UPLC-MS/MS). Multiple logistic regression was applied to evaluate the relationship between PFAS and URSA risk. Perfluorooctanoic acid (PFOA, median: 6.18 ng/mL), perfluorooctane sulfonate (PFOS, median: 4.10 ng/mL), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, median: 2.27 ng/mL) were the predominant PFAS in the controls. Exposure to 6:2 Cl-PFESA [adjusted odds ratio (aOR) = 1.18 (95% CI: 1.00, 1.39)] and hexafluoropropylene oxide dimer acid (HFPO-DA) [aOR = 1.35 (95% CI: 1.15, 1.59)] were significantly associated with increased risks of URSA. Women with older age (>30 years old) had a stronger association between PFAS and URSA. Our results suggest that emerging PFAS alternatives may be an important risk factor for URSA., (Copyright © 2022. Published by Elsevier Inc.)

Occupational and environmental Sb exposure has been associated with increased risk of respiratory diseases and lung cancer, but the toxicities and molecular mechanisms of Sb have been less investigated. In the present study, we first analyzed the Sb toxicity profile of lung adenocarcinoma A549 cells, and found that Sb dose-dependently decreased the cell viability and arrested cell cycle at G2/M but did not induce apoptosis. We next investigated the role of reactive oxygen species (ROS) involved in Sb-induced cytotoxicity. The results showed that Sb did not significantly induce cytosolic ROS production by NADPH oxidase (NOX) and the NOX inhibitors did not ameliorate the Sb-induced cell viability loss in A549 cells. However, the level of mitochondrial ROS (mtROS) was significantly increased in Sb-exposed cells and the mitochondria-targeted antioxidant significantly improved cell viability. These results suggested that mitochondria but not NOX is the major source of ROS production and mtROS plays a critical role in Sb-induced cytotoxicity. Furthermore, we found that Sb induced mitochondria dysfunction including the significant decrease of ATP level and mitochondrial membrane potential. Finally, Sb exposure decreased the activity of complex I and complex III, the level of -SH and GSH in mitochondria, and the activity of mitochondrial GR, GPx and TrxR, but increased the mitochondrial SOD activity, suggesting the disruption of mitochondrial redox homeostasis. Taken together, these findings suggested that Sb impaired mitochondrial redox homeostasis, resulting in formation of mtROS, thereby inhibited mitochondrial function and led to cytotoxicity., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The conversion of neuraxial anesthesia (NA) to general anesthesia (GA) during a cesarean section (CS) may be associated with a higher risk of neonatal morbidity by adding the undesirable effects of both these anesthesia techniques. We aimed to compare the neonatal morbidity of non-elective CS performed after conversion from NA to GA (secondary GA) vs. that after GA from the outset (primary GA)., Methods: We performed a monocentric retrospective study at the Angers University Hospital (France). All non-elective CSs performed under GA between January 2015 and December 2019 were included. The CSs were classified using a three-color coding system (green for non-urgent delivery, orange for urgent CS, and red for very urgent CS). The primary neonatal outcome was a composite of umbilical artery pH <7.10 or 5-min Apgar score <7. The crude and adjusted odds ratios (OR) for the risk of neonatal morbidity associated with secondary GA were estimated., Results: We included 247 patients, of whom 101 (41.3%) had a secondary GA and 146 (58.7%) had primary GA. In the secondary GA group, 86.1% (87/101) had epidural anesthesia and 13.9% (14/101) had spinal anesthesia. Multivariate analysis showed no difference in neonatal morbidity between the two groups (adjusted odds ratio 1.18, 95% CI 0.56 to 2.51)., Conclusions: Our study found insufficient evidence to identify a difference in neonatal outcomes between secondary compared with primary GA for CS, regardless of the level of emergency. However, our study is underpowered and additional studies are needed to confirm these data., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The use of bisphenol A (BPA) has been substantially limited since 2010 due to its toxicity to human health. A group of bisphenol analogues that are structurally similar to BPA have been developed as the alternatives and used widely. The reproductive toxicity of these emerging chemicals has caused substantial concerns in recent years. Whether bisphenol analogues affect miscarriage, especially unexplained recurrent miscarriage (URM), remains to be explored. We conducted a hospital-based, case-control study with 1180 URM cases and 571 controls in China from 2014 to 2016. Concentrations of six bisphenol analogues (BPA, BPAF, BPAP, BPB, BPP and BPS) were measured in the urine samples collected at median intervals of 7.6 months after last miscarriage (interquartile ranges: 4.8, 14.7 months). Multiple logistic regression, Bayesian kernel machine regression (BKMR) and quantile g-computation (q-gcomp) were used to assess the relationship of bisphenol analogues with URM risk. We observed significantly higher levels of all urinary bisphenols in the cases than the controls. After controlling for potential confounders, bisphenol analogues were significantly associated with increased odds of URM in varying degrees. A dose-response pattern was observed for the associations of BPAF, BPAP and BPB quartiles with URM. The mixed exposure of six bisphenol analogues was positively associated with the risk of URM (adjusted odds ratio (aOR) = 1.25; 1.11-1.42), which was mainly driven by BPAP (60.1%), BPAF (25.1%) and BPA (14.8%). After age stratification, the risks tended to be higher in women aged 30 years or older, compared to women <30 years. Our large case-control study indicates that environmental exposure to bisphenol analogues is associated with an increased risk of URM. Older women may be more vulnerable to the insult., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Regulatory B cells (Bregs) play an important role in maintaining immune homeostasis and have the potential to induce tolerance. Previous work has found that Breg cells are involved in heart transplantation tolerance. However, the effect of Breg on the transplantation tolerance and the underlying mechanisms remain to be clarified., Methods: Using a within-species heart transplantation model, we aimed to investigate the role of CD19 + CD5 + CD1d high Bregs isolated from transplanted mice in preventing transplant rejection in vivo. We also explored the effects of CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitin ligase on Breg-mediated prolongation of survival in heart transplant (HT) mice, and the regulatory effects of downstream Cdk4 and Cdk6 proteins on dendritic cells (DCs), which clarified the function and molecular mechanism of Breg cells in HT mice., Results: Our data suggest that adoptive transfer of the transplanted Bregs served as an effective tolerance-inducing mechanism in HT mice and was involved in the CD40-TRAF6 signaling pathway in DCs. Moreover, DCs collected from the Breg treated HT mice also prolonged the survival of HT mice. Furthermore, DC-specific knockout of TRAF6 diminished Breg-mediated prolongation of survival in HT mice. Interestingly, gut microbes from donors increased the survival of cardiac allografts both in both the absence and presence of Bregs but were not implicated in CD40-TRAF6 signaling., Conclusions: These findings reveal a role of Breg cells in the induction of transplantation tolerance through the blockade of the CD40-TRAF6 signaling pathway, which might be used in the treatment of HT in the clinic., Competing Interests: Disclosure Statement The authors declare that there are no competing interests. This work was supported by grants from the National Natural Science Foundation of China (No. 81670350), the National Natural Science Foundation of China (No. 81802887), the National Natural Science Foundation of China (No. 81603340), the Natural Science Foundation of Zhejiang Province, Zhejiang, China (No. LQ19H070002), the Natural Science Foundation of Zhejiang Province, Zhejiang, China (No. LGF18H020006) and the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No. 2019RC228)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Research Question: Does late-follicular phase progesterone elevation have a deleterious effect on embryo euploidy, blastocyst formation rate and cumulative live birth rates (CLBR)?, Design: A multicentre retrospective cross-sectional study including infertile patients aged 18-40 years who underwent ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol and preimplantation genetic testing for aneuploidies (PGT-A) followed by a freeze-all strategy and euploid embryo transfer between August 2017 and December 2019. The sample was stratified according to the progesterone concentrations on the day of trigger: normal (≤1.50 ng/ml) and high (>1.50 ng/ml). Moreover, sensitivity analyses were performed to determine whether different conclusions would have been drawn if different cut-offs had been adopted. The primary outcome was the embryo euploidy rate. Secondary outcomes were the blastocyst formation rate, the number of euploid blastocysts and CLBR., Results: Overall 1495 intracytoplasmic sperm injection PGT-A cycles were analysed. Late-follicular phase progesterone elevation was associated with significantly higher late-follicular oestradiol concentrations (2847.56 ± 1091.10 versus 2240.94 ± 996.37 pg/ml, P < 0.001) and significantly more oocytes retrieved (17.67 ± 8.86 versus 12.70 ± 7.00, P < 0.001). The number of euploid embryos was significantly higher in the progesterone elevation group (2.32 ± 1.74 versus 1.86 ± 1.42, P = 0.001), whereas the blastocyst formation rate (47.1% [43.7-50.5%] versus 51.0% [49.7-52.4%]), the embryo euploidy rate (48.3% [44.9-51.7%] versus 49.1% [47.7-50.6%], the live birth rate in the first frozen embryo transfer (34.1% versus 31.1%, P = 0.427) and CLBR (38.9% versus 37.0%, P = 0.637) were not significantly different between the two groups., Conclusions: Euploidy rate and CLBR do not significantly differ among PGT-A cycles with and without late-follicular progesterone elevation in a freeze-all approach., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To report our experiences with an extraction technique using a prebent, curved needle placed under deeply located single-rod implants to aid in removal., Study Design: We conducted a retrospective case series of all patients who were referred for removal of a deeply located or nonpalpable implant to one single specialized center between 2002 and 2019 by screening the database of the private office for "complex implants removals" or "nonpalpable implant" as a result for consultation. After implant-localization via high-resolution ultrasound, we performed a standard incision along the axis of the rod under local anesthesia. We fixed the rod by insertion of a curved needle directly beneath it piercing it through the tissue to the opposite side of the skin. After dissection of the subcutaneous tissue, we palpated the rod above the needle, grasped and removed it. In case of subfascial or intramuscular locations, we applied retractors and opened the fascia along the axis of the device to attempt removal., Results: Of 117 referrals, medical records of 95 patients provided sufficient information to be included in our analysis. We could not palpate 81 (85%) devices and questionably palpate 14 (15%) implants. We successfully extracted all implants using this technique with an average removal duration of 30 minutes (SD +/- 6.8). Five (5.3%) patients noted intraoperative discomfort with 3 of them describing transient dysesthesia in the fingers innervated by the median nerve, which disappeared within a maximum of 48 hours., Conclusion: Following the described protocol, this novel technique reliably facilitates removal of nonpalpable or deeply located etonogestrel implants., Implications: This series of nonpalpable implants, all of which have been removed with the same standardized technique provides evidence that the given protocol permits successful extraction., (Copyright © 2021. Published by Elsevier Inc.)

Research Question: Can cumulus cells be used as a non-invasive target for the study of determinants of preimplantation embryo quality?, Design: Cumulus cells were collected from monosomy 21, trisomy 21 and euploid embryos and subjected to RNA sequencing analysis and real-time polymerase chain reaction assays. The differential gene expression was analysed for different comparisons., Results: A total of 3122 genes in monosomy 21 cumulus cells and 19 genes in trisomy 21 cumulus cells were differentially expressed compared with euploid cumulus cells. Thirteen of these genes were differentially expressed in both monosomy and trisomy 21, compared with euploid, including disheveled segment polarity protein 2 (DVL2), cellular communication network factor 1 (CCN1/CYR61) and serum response factor (SRF), which have been previously implicated in embryo developmental competence. In addition, ingenuity pathway analysis revealed cell-cell contact function to be affected in both monosomy and trisomy 21 cumulus cells., Conclusions: These findings support the use of cumulus cell gene expression analysis for the development of biomarkers evaluating oocyte quality for patients undergoing fertility preservation of oocytes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research Question: Does endometrial thickness (EMT) predict adverse neonatal outcomes in singleton pregnancies after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) frozen embryo transfer (FET)?, Design: This retrospective study involved 13,383 women undergoing IVF/ICSI FET cycles between January 2010 and December 2018 in Women's Hospital of Zhejiang University. The primary outcome was preterm delivery (PTD). The secondary outcomes were small for gestational age (SGA), large for gestational age (LGA) and low birthweight (LBW)., Results: A total of 13,383 FET cycles resulting in 5220 singleton live births and 8163 failed cycles were included. Multiple spline regression visualization showed an increasing risk of PTD and LBW for a thin EMT. By comparing multiple cut-off points using area under the curve, a cut-off point of 8 mm was identified, which was used to categorize EMT. A reference point of EMT greater than 8 mm was used; after adjusting for covariates, individuals with EMT less than 8 mm had an adjusted odds ratio of 1.75 (95% CI 1.30 to 2.34) for PTD, 1.57 (95% CI 1.09 to 2.26) for LBW, 0.97 (95% CI 0.63 to 1.50) for SGA and 1.04 (95% CI 0.79 to 1.37) for LGA. Additional analyses showed similar increasing risk with a thin endometrium for both PTD with and without caesarean section, and PTD with low and normal birthweight percentiles., Conclusion: A clinical cut-off point of 8 mm has been identified, below which risk of PTD and LBW increases in women undergoing IVF/ICSI., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality., Methods: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders., Result(s): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM 2.5 and PM 10 ), O 3 and NO 2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO 2 appeared to influence semen quality throughout spermatogenesis., Conclusion(s): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The human placenta is vulnerable to environmental pollutants, but the associations between exposure to multiple, correlated metals and placental characteristics have not been studied., Methods: The current study population was derived from the Hangzhou Birth Cohort Study. Whole blood and urine samples were collected from mothers during 20-28 gestational week. The concentrations of 11 metals in blood and 11 metals in urine were evaluated by inductively coupled plasma mass spectrometry. The data on placental characteristics and birth weight were retrieved from medical records. The elastic net (ENET) model combined with unpenalized regression model was employed to estimate the relationship between levels of metals and placental characteristics (placental weight, chorionic disc area, chorionic disc eccentricity, placental thickness, placental-fetal birth weight ratio) and birth weight. Mediation analysis was performed to explore the mediated effect of placenta on the association of prenatal metals exposure with birth weight., Results: Among 512 participants with urine metal levels, the ENET model retained Cadmium (Cd) and Selenium (Se) for placental weight. Further unpenalized regression model including Cd and Se simultaneously showed that one-unite increased natural-logarithm (ln)-transformed urine creatinine corrected (CC) Cd levels was associated with reductions in placental weight of -7.2 g (95% confidence interval (CI): -14.0, -0.4). Among 483 participants with blood metal levels, similarly, blood Cd levels were negatively associated with placental weight (β = -7.5, 95% CI: -17.0, 1.9). Furthermore, mediation analysis demonstrated that urine CC-Cd level was associated with a 21.3 g decrease (95% CI: -42.0, -2.5, p = 0.024) in birth weight through a reduction in placental weight, while blood Cd levels presented a negative association at borderline significance., Conclusion: Our findings suggest a mediation effect of the placenta in the relationship between prenatal Cd exposure and lower birth weight. Additional studies with repeated assessment of exposure and more placental parameters are warranted to confirm this relationship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Embryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET)., Materials and Methods: This retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis., Results: Top-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33-1.89) and pregnancy complications (95% CI 0.12-7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05-1.22) and pregnancy complication (95% CI 1.01-1.29), respectively., Conclusion: Clinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder resulting in absent puberty and infertility. The genetic architecture is complex with multiple loci involved, variable expressivity, and incomplete penetrance. The majority of cases are sporadic, consistent with a disease affecting fertility. The current study aims to investigate mosaicism as a genetic mechanism for CHH, focusing on de novo rare variants in CHH genes., Methods: We evaluated 60 trios for de novo rare sequencing variants (RSV) in known CHH genes using exome sequencing. Potential mosaicism was suspected among RSVs with altered allelic ratios and confirmed using customized ultradeep sequencing (UDS) in multiple tissues., Results: Among the 60 trios, 10 probands harbored de novo pathogenic variants in CHH genes. Custom UDS demonstrated that three of these de novo variants were in fact postzygotic mosaicism-two in FGFR1 (p.Leu630Pro and p.Gly348Arg), and one in CHD7 (p.Arg2428*). Statistically significant variation across multiple tissues (DNA from blood, buccal, hair follicle, urine) confirmed their mosaic nature., Conclusions: We identified a significant number of de novo pathogenic variants in CHH of which a notable number (3/10) exhibited mosaicism. This report of postzygotic mosaicism in CHH patients provides valuable information for accurate genetic counseling.

Study Objective: To evaluate the levonorgestrel-releasing intrauterine system (LNG-IUS) to prevent the recurrence of endometrial polyps (EPs) after hysteroscopic polypectomies in premenopausal female patients., Design: A retrospective cohort study., Setting: A tertiary-care women's hospital., Patients: A total of 451 premenopausal female patients underwent hysteroscopic polypectomies between January 1, 2016, and December 31, 2017., Interventions: Treatment with LNG-IUS after hysteroscopic polypectomies., Measurements and Main Results: After the hysteroscopic polypectomies and placement of LNG-IUS, transvaginal ultrasounds were performed every 6 months to measure the recurrence of EPs. Overall, 5 (3.47%) of 144 patients in the LNG-IUS cohort and 49 (15.96%) of 307 patients in the control cohort experienced EP recurrence within the follow-up period of up to 3 years. The recurrence exhibited a strongly negative correlation when LNG-IUS was inserted (relative risk, 0.218; 95% confidence interval, 0.089-0.535; p <.05), but this did not significantly correlate with age, polyp size, number of polyps, previous history of polypectomy, and abnormal uterine bleeding. For the LNG-IUS and control cohorts, the recurrence in the first postoperative year was 1.39% and 6.19%, respectively, and 5.41% and 19.23% in the second postoperative year, respectively., Conclusion: LNG-IUS reduces the recurrence of postoperative EPs in premenopausal patients., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for assisted reproductive technologies. Combining these trends, it makes sense that clinicians are eager to understand and exploit the microbiome of their patients, i.e. the reproductive microbiome, in order to help them achieve their goal of becoming parents. This paper aims to provide an overview of the current and future research into the reproductive microbiome in relation to fertility and also share clinical practice recommendations for physicians who are new to this field or unsure about how they can utilise what is known to help their patients., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Sex education programs need to modify their focus in light of changing societal norms and increasing exposure to pornography. This study investigates what adolescents want to know about the sexuality of the opposite sex. This will allow practitioners to adjust sex education curricula to the needs of adolescents, thereby supporting the establishment of healthy, respectful, and sexually fulfilling relationships., Methods: Two thousand three hundred forty-three adolescents from the age of 11-19 years (123 classes) were asked to formulate questions addressed to the opposite sex as part of peer-led sex education classes, where girls and boys were divided into separate groups. Groups of 10-12 individuals each formulated about 11 questions, resulting in a total of 2,625 questions. The questions were categorized using content analysis., Results: The largest portion of questions addressed sexual interaction (35.8%), with many questions further addressing sexual preference (e.g., oral sex, sex positions) and the logistics and qualitative aspects of first-time sexual intercourse. Adolescents were also interested in questions about the body (e.g., anatomy, body hair, 15.2%), relationships (e.g., love, dating, 13.9%), ideal characteristics of men/women (10.5%), masturbation (10.1%), and pornography (7.3%)., Conclusion: Adolescents show a high degree of interest in understanding the feelings and perceptions of the opposite sex. Acquiring this knowledge could be beneficial in building emotionally and physically fulfilling relationships. To increase adolescents' sexual and relationship competence, sexual education curricula should encompass pleasure and desire aspects of sexuality, initiating and managing relationships, societal ideals, and addressing pornography, in addition to sexual and reproductive health knowledge., (Copyright © 2020. Published by Elsevier Inc.)

Objective: The purpose of this study was to define the pregnancy and oncologic outcomes after fertility-sparing treatment of atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and early-stage endometrioid endometrial cancer (EEC)., Materials and Methods: The retrospective cohort study included patients who had applied to Başkent University's Ankara Hospital between January 2007 and October 2018 with either AH/EIN (n: 27; Group A) or EEC (n: 30; Group B), and who had the desire to preserve their fertility. The medical records of all patients included in the study were reviewed retrospectively from the hospital records., Results: There were 2 (7.4%) and 5 (16.7%) recurrences, whereby one patient from Group A and two patients from Group B underwent staging surgery. In Group A, 8 patients attempted pregnancy after their treatment and 4 of them (50%) became pregnant, while 3 of them (37.5%) had a live birth. In Group B, there were 17 patients who wanted to become pregnant following treatment of the disease; 8 of them (47%) became pregnant after treatment, 5 of them (16.6%) had a live birth, 1 experienced intrauterine exitus (at 21st gestational week, 350 g), and 2 currently have ongoing pregnancies., Conclusion: Hysteroscopic resection of visible lesions and full endometrial curettage prior to hormonal therapy as a fertility-preserving approach for women of reproductive age with endometrial malignancies can achieve promising oncologic and obstetric responses., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Published by Elsevier B.V.)

Epidemiological studies have shown associations between exposure to environmental extremely low frequency magnetic fields (ELF-MF) and health effects, but the mechanisms of ELF-MF induced biological effects remain unclear. We hypothesized that ELF-MF may regulate functions of tissues or cells via its effects on surrounding environment, e.g., culture medium. To test this hypothesis, we investigated the effects of 50 Hz MF on the relative permittivity of zebrafish embryos culture medium as well as of MF-exposed medium on zebrafish embryos development. The responses of medium to 50 Hz MF exposure were evaluated by a phase-sensitive surface plasmon resonance (SPR) system. The results demonstrated that MF treatment decreased relative permittivity of zebrafish embryos medium in a dose and time-dependent way. Interestingly, the decreased permittivity induced by MF exposure gradually recovered and approached to the base level when the exposure was removed off. However, MF-exposed medium did not trigger adverse consequences of embryos during zebrafish embryonic development, including mortality, malformation, hatching and heart rate when the MF pre-exposed medium was subjected to one cell-stage embryos. Moreover, the MF-exposed medium did not induce apoptosis of zebrafish embryos at 48 and 72 h post fertilization. Our data demonstrated that the relative permittivity of zebrafish embryos medium was decreased by MF exposure, whereas this decrease failed to result in abnormal development of zebrafish embryos., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Research Question: Does calcium ionophore treatment of oocytes improve fertilization rate, embryo development and outcomes in specific groups of infertile couples?, Design: This retrospective cohort study involved 796 couples undergoing oocyte activation with calcium ionophore (A23187) after intracytoplasmic sperm injection (ICSI) between 2016 and 2018. All metaphase II oocytes were exposed to 5 μmol/l ionophore for 15 min immediately after ICSI, cultured in vitro to the blastocyst stage, and transferred to the uteri of recipients on day 5 or cryopreserved for transfer in the next cycle. The previous cycles of the same patients formed the control group., Results: Among 1261 ICSI cycles and 796 ICSI-artificial oocyte activation (ICSI-AOA) cycles, implantation, positive beta-HCG, clinical pregnancy and live birth rates were significantly (P < 0.05 to P < 0.001) improved for all groups, compared with previous cycles, except live birth rate in women with primary ovarian insufficiency (POI). Compared with previous cycles, rates of blastulation (all P < 0.001) and high-quality blastocysts (P < 0.05 to P < 0.001) were increased significantly for couples with male factor (oligoasthenoteratozoospermia [OAT]), unexplained infertility and couples with both factors in the ICSI-AOA cycles. High-quality blastocyst rate was increased in couples with polycystic ovary syndrome (PCOS) (P = 0.0453). Miscarriage rates were decreased significantly (P < 0.05 to P < 0.001) in couples with OAT, PCOS and unexplained infertility in the treatment cycles. No significant differences were found for fertilization rate, embryo development or live birth rate in patients with POI between both groups., Conclusions: Artificial oocyte activation was able to 'rescue' the poor reproductive outcomes in certain types of infertile couples with history of failure to achieve pregnancy., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the specific characteristics of sexual activity in women with endometriosis compared with women without endometriosis?, Design: Multicentre case control study. Participants were recruited from university hospitals, district hospitals and doctor's offices in Germany, Switzerland and Austria. A total of 565 women with endometriosis were pair-matched to 565 control women by age and ethnic background. Diagnosis of endometriosis was confirmed by histology, and disease stage was classified according to American Society for Reproductive Medicine criteria. Data on sexuality were collected using selected questions from the Brief Index of Sexual Function and the Sexual History Form., Results: Altogether, 69.1% of women with endometriosis and 77.8% of control women engaged in sexual activity during the month before the study period (P < 0.001). Overall, 42.3% of endometriosis-affected women and 30.5% of the control women desired a higher frequency of sexual activity (P < 0.001). Petting, foreplay and vaginal sexual intercourse were reported to be practised less often by women with endometriosis. Frequencies for masturbation, reciprocal masturbation, oral and anal sex were similar in both groups. Dyspareunia was negatively associated with sexual activity (OR 2.42, 95% CI 1.26 to 4.63), whereas chronic pain showed no association with sexual activity (OR 1.35, 95% CI 0.93, 1.96)., Conclusions: Women with endometriosis have lower frequencies of petting, foreplay and vaginal sexual intercourse than control women; this difference has to be attributed, at least in part, to dyspareunia. Potentially pain-free sexual options are used to a limited degree. As endometriosis-affected women desire higher levels of sexual activity, sexual counselling should be included in medical support., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: To evaluate in vitro fertilization (IVF) outcomes of proximal fallopian tube embolization by interventional radiology compared with laparoscopic salpingectomy before embryo transfer (ET) in patients with hydrosalpinx., Design: A single-center, off-label, nonrandomized prospective study., Setting: Academic university hospital., Patients: One hundred fifty-five patients with hydrosalpinx were identified on ultrasound or hysterosalpingography desiring IVF between April 2016 and December 2017., Interventions: Radiologically guided tubal occlusion with embolization microcoils (RTO-EM) and laparoscopic salpingectomy., Measurements and Main Results: Of the 155 analyzed patients, 42 were treated with RTO-EM and 113 with laparoscopic salpingectomy. The subsequent IVF outcomes, including implantation, clinical pregnancy, miscarriage, ectopic pregnancy, and ongoing pregnancy (i.e., a fetal heartbeat on ultrasound beyond 10 weeks) were compared between the 2 groups. Implantation and clinical pregnancy per ET cycle in the RTO-EM group were similar to that of the salpingectomy group (26.7% vs 30.2% [p = .51] and 39.0% vs 45.3% [p = .40], respectively), with a similar miscarriage rate. There was no statistically significant difference in ectopic pregnancies between the 2 groups. Moreover, no difference was detected in ongoing pregnancy per cycle between the 2 groups (33.9% vs 41.2%; p = .32). The ongoing-pregnancy rate per patient following RTO-EM was 47.6% (20 of 42) compared with 61.9% (70 of 113) following salpingectomy (odds ratio, 0.56; 95% confidence interval, 0.27-1.14; p = .11)., Conclusion: Pregnancy in the RTO-EM group was comparable to the salpingectomy group in patients with hydrosalpinx before ET treatment. RTO-EMs may be an alternative to salpingectomy for patients with hydrosalpinx planning for IVF-ET., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Research Question: There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF., Design: This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-α and interleukin-10 (IL-10) was analysed., Results: A comparison was made of the percentage and gene expression of CD56 bright CD16 - uterine natural killer (uNK), CD56 dim CD16 + natural killer cells, CD56 - CD16 + natural killer cells and TregCD25 + CD4 + FoxP3 + cells, uNK binding to the HLA-C tetramer, and TNF-α and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles., Conclusions: Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the prevalence of female sexual dysfunction (FSD) and depression in primary infertile women with 25-Hydroxyvitamin D3 (25-OH VD) deficiency undergoing in-vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) treatment., Materials and Methods: A total of 80 women with 25-OH VD3 deficiency (<20 ng/mL = group 1), 80 women with 25-OH VD3 insufficiency (20-29.9 ng/mL = group 2), and 80 women with a normal 25-OH VD3 level (30-60 ng/mL = group 3) were included the study. Female sexual function and depression were measured using the Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI)., Results: No statistically significant differences were found among the groups in terms of demographic characteristics, baseline and laboratory parameters. Statistically significant differences were observed among the groups with regard to FSD and depression. The FSFI (group 1 = 22.46 ± 2.13, group 2 = 25.82 ± 2.13 and group 3 = 28.66 ± 2.13, respectively) and sexual domain scores were low in women with 25-OH VD deficiency, and the number of women with depression (BDI score ≥ 17) was high (p < 0.05). Correlation analysis showed that the sexual domain scores were positively correlated with the 25-OH VD level, and the BDI score showed a significant negative correlation with the total FSFI score and 25-OH VD levels., Conclusion: The 25-OH VD status was associated with FSD and depression and that the degree of sexual dysfunction could depend on the severity of 25-OH VD levels. Further studies are needed to elucidate this issue., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)