Polychlorinated biphenyls and the risk of endometriosis: Systematic review and meta-analysis.

OBJECTIVE: We aimed to collect recent findings for a deeper understanding of the association between human exposure to polychlorinated biphenyls (PCBs) and endometriosis development. METHODS: Web of Science, PubMed, Scopus, Google Scholar, and Embase were searched based on inclusion criteria from 2000 to the end of 2020. No filter was exerted to limit the language of publications and geographical restriction. Odds ratios (OR) using the random-effects model and the corresponding 95% confidence interval (CI) were calculated for each included study. RESULTS: Fourteen studies were included in our analyses. The pooled OR and 95% CI for PCB was 1.96 (1.31 to 2.93). Despite being statistically significant, there was evidence of moderate heterogeneity (I2 = 63%, P = 0.001, τ2 = 0.32). Findings from our subgroup analyses showed a significant association between PCB exposure and endometriosis among European population (OR = 3.66, 95% CI: 2.08-6.44). Also a positive association was detected between PCB exposure and an increased odds of endometriosis in studies with laparoscopy (OR = 2.32, 95% CI: 1.16-4.63) or surgery confirm of controls (OR = 1.39, 95% CI: 1.02-1.89). Moreover, according to matched-pairs design, a significant association between PCB exposure and endometriosis development was detected (OR = 1.51, 95% CI: 1.04-2.18), also heterogeneity decreased in studies with matched-pairs design (I2 = 30.4%). CONCLUSIONS: Findings of this study confirm an association between endometriosis and exposure to PCB. However, more primary studies using proper methodology are needed to confirm this association.

Stages of endometriosis: Does it affect oocyte quality, embryo development and fertilization rate?

OBJECTIVE: To investigate the effect of endometriosis and its different stages over Intracytoplasmic Sperm Injection (ICSI) outcomes among infertile women without previous history of ovarian surgery. METHODS: A total of 440 women enrolled in ICSI cycles were recruited and divided into two groups: endometriosis (n=220) and control group (n=220). Endometriosis patients without previous surgical treatment and with diagnostic laparoscopy were further stratified based on disease stage. Clinical and laboratory parameters, ovarian reserve markers, the number and quality of oocytes and embryos and fertilization rate were analyzed and compared among the various severity grades of endometriosis and the control group. RESULTS: Patients with advanced endometriosis had significantly fewer retrieved oocytes with small effect size (p<0.001, η2=0.04), lower metaphase II oocytes (p<0.001, η2=0.09) and fewer total numbers of embryos (p<0.001, η2=0.11) compared with less severe disease or women with tubal factor infertility. The fertilization rate in women with severe endometriosis was similar to that of the control group and in those with minimal/mild endometriosis (p=0.187). CONCLUSIONS: Severe endometriosis negatively affects ovarian response, oocyte quality and embryos. However, fertilization rate is not different among the various stages of endometriosis.

Resistin and chemerin levels in follicular fluid of infertile women with endometriosis undergoing ICSI.

Chemerin and resistin are two adipocytokines involved in inflammatory processes that may paly a role in the development of endometriosis. The purpose of the current study was to examine the levels of chemerin and resistin in the follicular fluid (FF) of endometriosis patients and additionally, assess the association of FF chemerin and resistin with the severity of endometriosis and the number of mature oocyte and embryos. A total of 80 reproductive-aged women who underwent intracytoplasmic sperm injection and embryo transfer were evaluated in this study. FF samples were obtained from subjects with (n = 40) and without endometriosis (n = 40). The concentrations of chemerin and resistin were examined using ELISA. The Resistin FF level was significantly (p-value=.03) higher in women with endometriosis than women without endometriosis, while the effect size was medium (d = 0.47). There was no significant difference in Chemerin concentration between the two groups of this study. Results also showed a tendency towards the increase of FF values of resistin and chemerin in endometriosis patients with stage III-IV than stage I-II; however, this difference was not significant. No significant correlations were found between FF levels of resistin and chemerin with the number of mature oocyte and embryos. Thus, elevated FF resistin levels may be associated with endometriosis.IMPACT STATEMENTWhat is already known on this subject? To our knowledge, no studies have investigated chemerin levels in follicular fluid of infertile women with endometriosis undergoing ICSI. Although follicular fluid levels of resistin have been previously studied in endometriosis, it has not been studied yet whether its level is associated with the number of oocyte and embryos.What do the results of this study add? Our results indicate that significantly increased resistin levels in follicular fluid may be associated with the presence of endometriosis.What are the implications of these findings for clinical practice and/or further research? The findings are promising in that significantly increased resistin levels may add to the knowledge of the pathophysiology of endometriosis.

Receptivity markers in endometrial mesenchymal stem cells of recurrent implantation failure and non-recurrent implantation failure women: A pilot study.

AIM: Endometrial mesenchymal stem cells (eMSC) have a vital role in regeneration of endometrium during menstrual cycles. Since it has been suggested that (eMSC) likely play a role in uterine receptivity and establishment of pregnancy, we aimed to evaluate the expression levels of five most known receptivity markers-Integrin (ITG) ß1, Rac1, HoxA11, ITGß3 and Noggin-in eMSC of recurrent implantation failure (RIF) and non-RIF women. METHODS: Human eMSC were isolated from menstrual blood (MB) of RIF and non-RIF women. The isolated eMSC characterized based on their morphological and behavioral characteristics, expression of MSC-specific surface CD markers and their capacity of differentiation into osteocytes and adipocytes. The expression levels of the five mentioned receptivity markers were analyzed with real time reverse transcription polymerase chain reaction. RESULTS: Our findings revealed that RIF and non-RIF eMSC expressed all tested genes at different levels. ITGb1 expression in RIF eMSC was lower than its expression in non-RIF cells. On the other hand, all the other markers were expressed at higher levels in RIF eMSC than in non-RIF cells although only HOXA11 and ITG ß3 showed statistically significant (P < 0.05) higher expression levels. CONCLUSION: This pilot study on determination of the expression levels of uterine receptivity markers in eMSC interestingly indicated that RIF and non-RIF eMSC were different regarding the expression of these markers. Future studies using these findings can brighten up more the role of eMSC in the endometrium receptivity and establishment of pregnancy.

Elevated expression of IL-18 but not IL-1ß gene is associated with NALP3 and AIM2 inflammasome in Polycystic Ovary Syndrome.

Inflammasome complex mediated interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) production may be involved in immunopathogenesis of polycystic ovary syndrome (PCOS). Therefore, this study was conducted to investigate involved inflammasome pathways in PCOS. Therefore, inflammasome genes expression and serum level of IL-1ß were evaluated in 30 patients with confirmed PCOS and 30 women without PCOS. A remarkable increase in expression of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NALP3), absent in melanoma 2 (AIM2), IL-18 and associated speck-like protein containing a caspase recruitment domain (CARD); (ASC) genes in PCOS were observed (p < 0.05). In contrast, expression level of NALP1, NALP12, NLR family apoptosis inhibitory proteins (NAIP), NLR family caspase recruitment domain (CARD) domain containing 4 (NLRC4) and IL-1ß genes was not significant. Although the IL-1ß protein level in serum of COS patients with BMI ≥ 25 was significantly higher than PCOS patient with BMI < 25, but there was no significant difference in non-PCOS individuals with BMI < 25 or ≥25. Furthermore, significant correlation between expression of AIM2 (r = 0.83, p = 0.032) and NALP3 (r = 0.59, p = 0.0001) was observed with IL-18, while a positive correlation (r = 0.84, p = 0.0001) was revealed between NAIP and IL-1ß. Based on the obtained results on inflammasome components along with increased expression of IL-1ß especially in overweight patients, it can be concluded that IL-18 expression as well as IL-1ß is probably due to activation of AIM2, NALP3 or NAIP inflammasome, which may play a critical role in immunopathology of PCOS.

Infertility as a risk factor for breast cancer: Results from a hospital-based case-control study.

CONTEXT: Breast cancer is the most common cancer in women worldwide and its prevalence is increasing. AIMS: The aim of this study was to investigate the extent to which a history of infertility can present as risk factors for breast cancer. SETTINGS AND DESIGN: This was a hospital-based case-control study. SUBJECTS AND METHODS: In this study, 1177 women with breast cancer were participated for assessing the risk for this cancer. The control was 1204 women with self-reported free-cancer history who were matched in terms of age and residence. STATISTICAL ANALYSIS USED: Using logistic regression, it was examined whether infertility is a risk factor of case-control status in addition to marriage age, menarche age, body mass index, number of pregnancies, family history of breast cancer, and previous oral contraceptive use. The data were considered significant at P ≤ 0.05. RESULTS: Infertility history was reported in 12.5% (n = 147) of the cases and 5.8% (n = 70) of the controls. Infertility history was a relevant risk for case-control study in addition to other risk factors (odds ratio: 2.43; 95% confidence interval, 3.34-1.77). CONCLUSIONS: This study found that infertility may be as the main risk factor for breast cancer in Iranian women, therefore, doing breast screening in women who have one or more risk factors, must receive more emphasis.

Cytochrome P-450 1B1 Leu432Val Polymorphism Does Not Show Association With Breast Cancer in Northern Iranian Women With a History of Infertility.

The Cytochrome P-4501B1 (CYP1B1) Leu432Val polymorphism has been previously shown to be associated with some types of cancer and affects CYP1B1-mediated metabolism of various infertility drugs. To establish the frequency of CYP1B1 Leu432Val polymorphism among women with a history of infertility drug use, we studied the genotypes of 147 patients with breast cancer with a history of infertility and 150 cancer-free, infertile women (control group) in Northern Iran. A polymerase chain reaction-based restriction fragment length polymorphism assay was used to detect GG (Val/Val), CG (Leu/Val), and CC (Leu/Leu) genotype frequencies, which did not vary significantly between the 2 patient groups (P = .847). We established for the first time that the incidence of CYP1B1 Leu432Val polymorphism is 46.6% among women with infertility history and breast cancer in Northern Iran. Finally, our results do not show any significant association between CYP1B1 Leu432Val polymorphism and breast cancer in infertile women in this region, who have also received infertility treatment.

Risk Factors for Endometrial Cancer: Results from a Hospital-Based Case-Control Study

Objectives: The purpose of this investigation was to examine the association between endometrial cancer and possible etiological agents. Methods: A case-control study was conducted in Iran between March 2012 and May 2016. The demographic and reproductive factors of 205 women with endometrial cancer were compared, and 590 healthy cases were participated in the control group. For each endometrial cancer case, there were three controls, who were matched in terms of age and residence. The data were considered significant at p ≤0.05. Results: After adjusting the variables, the nulliparity (OR 6.23, 95% CI 2.86-13.59), the nulligravidity (OR 5.94, 95% CI 2.51-14.06), the positive family history of reproductive cancer (OR 4.97, 95% CI 2.33-10.59), the infertility history (OR 2.38, 95%CI 1.32-4.31), the obesity (BMI ≥25) (OR 1.71, 95% CI 1.16-2.52), the early menarche age (<12 years) (OR 2.10, 95% CI 1.17-3.75), and the hormonal contraception use (OR 1.69, 95% CI 1.15-2.49) were found to be associated with an increased risk of endometrial cancer. Nevertheless, the education level, the job of women, the marital age, the leisure activities, and the breast feeding were not found to be associated with the endometrial cancer after adjusting the variables. Conclusion: Scheduling of the screening program is vitally indispensable to identify endometrial cancer in women with nulliparity, nulligravidity and the positive family history of cancer. In addition, women with early menarche, those with the history of infertility, the obese ones, and those who use contraception pills need to be particularly aware of the potential risks.