Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study.

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

Melatonin enhances the developmental potential of immature oocytes from older reproductive-aged women by improving mitochondrial function.

Aims: To evaluate whether melatonin (MT) supplementation during in vitro maturation (IVM) of human oocytes can reverse the age-related decline in oocyte quality. Main methods: We enrolled 172 patients aged ≥35 years (older reproductive-aged women) and 83 patients aged <35 years (young women) who underwent in vitro fertilization between 2019 and 2022. We conducted IVM with and without 10 µM MT in immature oocytes of different ages. Oocyte fertilization and embryo development were observed using a stereomicroscope. We assessed the immunofluorescence intensity of mitochondrial function, measured the copy number of mitochondrial DNA (mtDNA), and examined the spindle and chromosome composition in in vitro mature stage II (IVM-MII) oocytes using immunofluorescence and second-generation sequencing. Key findings: MT supplementation significantly improved the redox level in the IVM medium and IVM-MII oocytes in older reproductive-aged women. It also significantly increased the proportion of circular mtDNA and the adenosine triphosphate content in IVM-MII oocytes. In addition, the IVM-MII oocytes obtained with MT supplementation showed a significant improvement in the normal composition of the spindle and chromosomes. Thus, the aged immature oocytes also showed significantly improved maturation and blastocyst formation rates owing to the role of MT. Significance: Supplementation with 10 µM MT in the IVM medium reverses the age-related decline in oocyte quality. Our findings provide a viable solution for enhancing fertility in older reproductive-aged women.

Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study : Serum Essential Trace Element Status in Women and the Risk of Endometrial Diseases: a Case-Control Study.

Endometrial diseases, including uterine fibroids, polyps, intrauterine adhesion, endometritis, etc., are the major causes of infertility among women. However, the association between essential trace element status in women and the risk of endometrial disease is limited and unclear. This study aimed to investigate this association using a case-control study design; a total of 302 women patients with endometrial diseases and 302 healthy women were included. Compared to women in the control group, serum selenium (Se) (p = 0.024) and zinc (Zn) (p = 0.017) levels were significantly lower, while copper (Cu) (p = 0.004) and molybdenum (Mo) (p = 0.005) levels were significantly higher among women with endometrial diseases. In addition, compared to women in the first quartile of the copper/zinc (Cu/Zn) ratio value group, the adjusted ORs (95% CIs) of endometrial diseases were 1.50 (1.05, 2.14), 1.68 (1.18, 2.39), and 1.47 (1.02, 2.10), respectively, in the second, third, and fourth quartile of the Cu/Zn ratio value group (p trend = 0.047). In addition, the results from restricted cubic splines showed that the dose-response relationships of serum levels of these essential elements with the risk of endometrial diseases were nonlinear for Se, Cu, and Zn and relatively linear for Mo and Cu/Zn ratio. The present study showed serum levels of Zn and Se among women with endometrial diseases were significantly lower compared to that among healthy women, while serum levels of Cu and Mo were significantly higher, in addition, the serum Cu/Zn ratio value was also significantly and positively associated with the risk of endometrial diseases.

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques.

Background: Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study. Objective: Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA. Methods: A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA. Results: Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant. Conclusion: The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

Effective treatment of ketamine-associated cystitis with botulinum toxin type a injection combined with bladder hydrodistention.

Objective Ketamine-associated cystitis (KAC) has been described in a few case reports, but its treatment in a relatively large number of patients has not been documented. This study aimed to describe our experience of treatment of 36 patients with KAC. Methods Thirty-six patients (30 males and 6 females, aged 19-38 years) with KAC, who had previously taken a muscarinic receptor blocker and/or antibiotics, but without symptomatic relief, were treated with botulinum toxin A injection combined with bladder hydrodistention. Urodynamic testing, and the O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI) were used to evaluate baseline values and improvement before and after the treatment. Results One month post-treatment, all patients achieved marked relief of symptoms. The nocturia time was markedly reduced, while bladder capacity, the interval between micturition, the void volume, and the maximum flow rate were remarkably increased at 1 month. Additionally, the ICSI and ICPI were significantly improved. Conclusion Botulinum toxin A injection along with bladder hydrodistention is effective for managing KAC.