Association of organophosphate flame retardant metabolite concentrations in follicular fluid with in vitro fertilization outcomes among infertile women.

Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a case[sbnd]control study

Perfluoroalkyl acids (PFAA) have been measured in ovarian follicular fluid from women using in vitro fertilization (IVF), although associations between follicular fluid PFAA and IVF outcomes have been inconsistent. We investigated the association between follicular fluid PFAA and embryo quality in women undergoing IVF. We prospectively enrolled 729 women undergoing IVF treatment in Guangxi province, China, from July 2018 to December 2018. We measured 32 PFAA, including branched isomers, in follicular fluid using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We applied restricted cubic splines, linear regression, and log-binominal regression models to investigate associations between follicular fluid PFAA and embryo quality, adjusting for confounding variables and investigated oocyte maturity as an intervening variable using causal mediation analysis. We further estimated the overall effect of the PFAA mixture on outcomes using Bayesian kernel machine regression (BKMR). We detected 8 of 32 measured PFAA in of follicular fluid samples. Higher PFAA concentrations were associated with fewer high-quality embryos from IVF. The high-quality embryo rates at the 50th percentile of linear perfluoro-1-octanesulfonate acid (n-PFOS), all branched PFOS isomers (Br-PFOS) and linear perfluoro--octanoic acid (n-PFOA) were [95% confidence interval (CI): , ], (95% CI: , ) and (95% CI: , ) lower, respectively, than the high quality embryo rates at the reference 10th percentile of PFAA. Oocyte maturity mediated 11.76% (95% CI: 3.18, 31.80%) and 14.28% (95% CI: 2.95, 31.27%) of the n-PFOS and n-PFOA associations, respectively. The results of the BKMR models showed a negative association between the PFAA mixture and the probability of high-quality embryos, with branched PFOS isomers having posterior inclusion probabilities of 1 and accounting for the majority of the association. Exposure to higher PFAA concentrations in follicular fluid was associated with poorer embryo quality during IVF. Branched PFOS isomers may have a stronger effect than linear PFOS isomers. More studies are needed to confirm these findings and to directly estimate the effects on pregnancy and live-birth outcomes. https://doi.org/10.1289/EHP10857.

Predictors of phthalate metabolites in urine and follicular fluid and correlations between urine and follicular fluid phthalate metabolite concentrations among women undergoing in vitro fertilization

Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called 'endocrine-disrupting chemicals' (EDCs) or 'endocrine disruptors', can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum. Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination. Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even when the analysis is adjusted for age, estradiol concentration, BMI, fertilization procedure and male subfertility as explanatory variables. The strong correlations between the EDC concentrations in serum and follicular fluid (r ≥ 0.93) allowed us to build regression models, which accurately predict EDC concentrations in the follicular fluid based on serum samples. An overall higher EDC contamination in the follicular micro-environment was associated with a decreased fertilization rate and consequently with a lower chance of an oocyte to develop into a high-quality embryo. In addition, EDC concentrations in serum were reliable predictors of the contamination status of the follicular micro-environment.

Ovarian follicular fluid levels of phthalates and benzophenones in relation to fertility outcomes

MTHFR gene polymorphisms (C677T, A1298C and G1793A) in infertile women with endometriosis and its correlation with follicular fluid and serum homocysteine: pilot study

Prenatal exposure to organophosphorus flame retardants and birth outcomes: A cross-sectional study in an e-waste area in China.

PurposeTo compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters.MethodsFifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol.ResultsThere was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels.ConclusionBeta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

Per- and polyfluoroalkyl substances (PFAS) have been associated with polycystic ovarian syndrome (PCOS), however, the evidence is limited. This study aimed to explore the associations between PFAS in the follicular fluid and PCOS, as well as the mediating role of steroid hormones. Forty women with PCOS undergoing treatment for infertility and 56 control participants were included in this study. The levels of 24 PFAS in the follicular fluid and sex hormones in serum were measured. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS were estimated by multivariable logistic regression. Correlation analysis and multiple linear regression revealed the associations between PFAS and steroid hormones. Bayesian kernel machine regression (BKMR) model was utilized to evaluate the associations between joint and individual PFAS exposure and PCOS. Additionally, in-vitro experiment with human ovarian granulosa cell line (KGN cells) was conducted. The study showed that perfluoro-n-octanoic acid (PFOA) and potassium perfluoro-1-octanesulfonate (PFOS) were the dominant PFAS in the follicular fluid samples, with the median concentration of 4.35 ng/mL and 5.22 ng/mL, respectively. Perfluoro-n-hexanoic acid (PFHxA) were correlated with increased incidences of PCOS (medium vs. low tertile: OR = 1.78, 95% CI: 0.18, 17.19). In the cases, a negative relationship was found between PFHxA and luteinizing hormone (LH; β = -0.44, 95% CI: -8.25, -0.03), while a positive relationship was observed between perfluoro-n-heptanoic acid (PFHpA) and LH (β = 0.504, 95% CI: 0.71, 21.31). PFOA was positively associated with estradiol (E2; β = 0.76, 95% CI: 1.52, 19.57). The BKMR model indicated that there might be a joint effect between PFAS mixtures and PCOS, with the posterior inclusion probabilities (PIP) of PFHxA was 0.983. In the cell experiments, PFOA, PFOS, and PFHpA exposure decreased the concentration of E2 (p < 0.05). PFHxA in follicular fluids was associated with the elevated odds of PCOS, and steroid hormones may play a role in the etiologic connection.

In assisted reproductive technology (ART), researchers have tried to predict in vitro fertilization (IVF) outcomes depending on follicular cells apoptosis. Previous reports suggested the B-cell lymphoma-extra-large (BCL-XL) as an apoptosis inhibitor in mammalian ovaries. Therefore, the present research aimed to correlate BCL-XL expression in blood and concentration in follicular fluid (FF) with some outcomes of IVF. A prospective case-control study on infertile women (n=80, mean age= 31.18± 6.04 years) who underwent an IVF program at Kamal Al-Samarai Hospital (Baghdad/Iraq), July 2021- January 2022. All women were split based on pregnancy outcome into two groups: the non-pregnant group (n=40) and the pregnant group (n=40). Samples of FF and blood were assembled at oocyte retrieval time. The BCL-XL mRNA expression was assessed with the Real-Time Quantitative Reverse Transcription-polymerase chain reaction (Real-Time qRT-PCR) technique, whereas the BCL-XL concentration in FF was investigated by sandwich enzyme-linked immunosorbent assay (ELISA). The BCL-XL concentration in FF from pregnant group (3.90 ng/ml ±1.16) raised significantly (P = 0.00) compared with non-pregnant group (1.90 ng/ml ± 0.63). Similarly, the BCL-XL mRNA expression in blood from pregnant group (0.73 ±0.31) raised significantly (P = 0.00) compared with non-pregnant group (0.34± 0.12). In addition, FF BCL-XL concentration associated significantly with fertilization rate (r= 0.399, P=0.048). The research proposed that the elevation of anti-apoptotic BCL-XL might assist in diminished apoptosis in pregnant women who underwent IVF treatment.

P-423: High BMP-15 levels in follicular fluid is associated with good oocyte and embryo quality

Association between exposure to perfluoroalkyl substances (PFASs) and risk of hyperemesis gravidarum.

Study question Is whether there is a metabolomic signature in the follicular fluid depending on oocyte quality and whether infertility may impact on this quality? Summary answer 46 metabolites were quantified via nuclear magnetic resonance spectroscopy in the follicular fluid, and each metabolite that was a biomarker of oocyte quality was pathology-specific. What is known already Literature confirmed that metabolomics had been valuable for exploring follicular fluid and the search for nutritive and non-nutritive biomarkers. There are currently no data in the literature concerning the homeostasis of this follicular fluid, and two options are possible: this fluid is a continuum of blood plasma, or it has its own homeostasis. Studies have highlighted follicular fluid qualitative and quantitative alterations in the metabolome due to one specific infertility pathology footprint and correlated in some instances to outcome measures of in vitro fertilization success but samples are pooled and there are no information concerning quality and competence oocyte assessment. Study design, size, duration 61 infertile patients who underwent in vitro fertilization (IVF) treatment with intracytoplasmic sperm injection (ICSI) from Femme Mère Enfant hospital (Bron, France) between 6th april 2022 and 12th may 2022 were included. Participants/materials, setting, methods 61 follicular fluids were collected individually and used for metabolomic profiling by nuclear magnetic resonance spectroscopy. A total of 46 metabolites were quantified. Metabolite concentrations in follicular fluid were compared with serum concentrations.Oocyte was considered mature if it has its first polar body and competent if it was able to develop into a blastocyst after culturing. In vitro fertilized oocytes were cultured and monitored with time-lapses incubation technology until day 5 or 6. Main results and the role of chance For 23 metabolites out of 46, follicular fluid exhibited lower concentrations than serum. Glucose and glutamine, which are among the most abundant metabolites, decreased by 54% (not significant) and 47% (P &amp;lt; 0.05) respectively. 7 metabolites exhibited higher concentrations in the follicular fluid than in the serum. An 85%-increase in lactate and a more-than-tenfold increase in pyruvate were noted (P &amp;lt; 0.05). The reverse ratios of lower substrates such as glucose and glutamine and higher waste products like lactate and pyruvate imply that the follicular fluid functions as a homeostatic compartment, being more influenced by exchange within follicular cells than by serum equilibration. The detected metabolic signatures of oocyte maturity and competence were all specific to the patient infertility-related pathology. The follicular fluid concentrations of aspartate, glucose, methionine and methylmalonate were significantly correlated to oocyte maturity in the control group (P &amp;lt; 0.05). For patients having endometriosis, asparagine concentration was significantly decreased by oocyte maturity (P &amp;lt; 0.05). For patients with diminished ovarian reserve, acetone concentration was significantly decreased by oocyte maturity (P &amp;lt; 0.05). The concentration of aspartate, that correlated with oocyte maturity, was also slightly decreased by oocyte competence, and for the patients with endometriosis the concentration of threonine was decreased by 30% by oocyte competence (P &amp;lt; 0.05). Limitations, reasons for caution Although 46 metabolites were well quantified, each metabolite that was a biomarker of oocyte maturity or competence was pathology specific. One major reason would be the high metabolite concentration variation observed between the different infertilities. This study indicates that the diagnosis of patients according to their infertility must be prior. Wider implications of the findings This study underlines the potential of follicular fluid metabolomics as a diagnostic avenue for oocyte-related becoming in order to enhance the selection of oocytes and improve outcomes in assisted reproductive and preservation fertility techniques. Trial registration number not applicable

Background Endometriosis (EM) affects 10% women of reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Kallistatin (KS) is an endogenous protein that regulates differential signaling pathways and biological functions. However, the function and the underlying molecular mechanism in EM and its correlation with in vitro fertilization (IVF) outcome have not been determined. The purpose of this study was to evaluate KS concentrations in follicular fluid (FF) of women with EM and controls women without EM who underwent IVF with embryo transfer (IVF–ET). Methods FF KS concentrations from 40 patients with EM and 40 non-EM patients were measured by ELISA. Results Compared with the non-EM patients, patients with EM had lower KS levels in FF (281.67 ± 104.60 vs. 490.70 ± 216.33 pg/ml). The rates of fertilization (61.64 ± 22.42 vs. 71.00 ± 24.39%), available embryo (45.96 ± 19.83 vs. 50.61 ± 26.26%), and top-quality embryo (12.71 ± 21.01 vs. 16.04 ± 16.87%) were significantly lower in the EM group than in the control group. The KS concentrations in the FF of women who conceived consequent to the treatment were significantly higher than those from women who did not in the combined EM and control groups. Conclusions These results indicate that the KS concentration in FF could be used as a predictor for IVF–ET outcomes. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM.

Treatment efficiency of chronic infertility does not exceed 40% when using in vitro fertilization (IVF) programs. Therefore, sufficient attention should be given to studies of pathogenetic mechanisms, identification and correction of the factors that adversely affect onset and outcomes of pregnancy. It is known that hypersecretion of cytokines interferes with implantation, but their relationship with immunoregulatory proteins is poorly understood for various types of infertility. The aim of present study was to investigate changes in cytokine contents (IL-8, IL-6, TNFα, IFNγ), lactoferrin and α2-macroglobulin concentration in follicular fluid and venous blood of women with infertility of various genesis, and to evaluate their effects upon results of the IVF programs. The studied proteins were determined in the samples obtained on the day of transvaginal puncture of follicles in 28 infertile women with external genital endometriosis, 38 cases of chronic endometritis, 31 women with polycystic ovary syndrome, 25 patients with adenomyosis, and in 37 women with pure tubal infertility factor (comparison group). According to IVF outcomes, the patients were retrospectively divided into those who became gravid, and women with pregnancy failure. In cases of external genital endometriosis, we have found reduced contents of chemoattractant IL-8 in follicular fluid and blood, as well decreased levels of lactoferrin, which modulates its synthesis and shows antiproliferative activity. In blood of non-pregnant women with tubal infertility associated with chronic endometritis, increased concentrations of pro-inflammatory TNFα and lactoferrin were revealed, thus suggesting presence of latent inflammation. Among women with polycystic ovary syndrome, the TNFα concentration in follicular fluid and blood was reduced, along with increased content of IFNγ. In cases of adenomyosis, the IFNγ levels in follicular fluid were increased, accompanied by reduced content of regulatory-transport α2-macroglobulin in blood samples. The revealed changes in cytokine concentrations and proteins which regulate their synthesis, in biological samples from infertile women may explain the ineffectiveness of IVF programs in a number of cases. Such an imbalance has a negative impact upon development of oocytes, growth of embryos, and their ability for implantation. It is important to continue further investigations of such pathogenetic factors in order to improve approaches providing better efficiency of IVF in chronic infertility treatment.