International attitudes towards medical and planned oocyte cryopreservation.

PURPOSE: This study aims to better understand the knowledge and attitudes of men and women internationally towards oocyte cryopreservation (OC). METHODS: An online 25-question survey was distributed internationally via email and social media. Knowledge and attitudes towards OC among different regions and genders were assessed. The study population consisted of adults from North America (NA, 15.7%), Southeastern and Eastern Europe (SE, 34.7%), Central and Western Europe (CWE, 12.7%), Asia (12.7%), and Middle East (ME, 8.9%). RESULTS: A total of 496 respondents initiated the survey and the completion rate was 80.2%. The mean (SD) age was 35.2 (12.1) years. Over 70% were aware of OC, but only 4.8% had previously undergone the procedure. Most considered ages 26-31 as optimal for OC and correctly identified conditions that could impact the chance of spontaneous conception. Significant differences were observed regarding etiologies that would render OC acceptable. Only in NA and ME did solid majorities strongly agree that it is acceptable to proceed with OC to allow more time to find the right partner or for professional opportunities. More similar opinions were observed between genders. When medical conditions existed, large majorities across all nationalities and genders strongly agreed that OC is acceptable. In NA, SE, and ME most respondents would consider or recommend OC for any reason, whereas most respondents in CWE and Asia would do that only for certain social reasons or medical necessity. CONCLUSION: A good understanding of OC was observed. Nationality appeared to impact opinions on appropriate indications for this procedure, though overall positive attitudes were documented.

The impact of cryopreserved sperm on intrauterine insemination outcomes: is frozen as good as fresh?

Introduction: Frozen sperm utilization might negatively impact cycle outcomes in animals, implicating cryopreservation-induced sperm damage. However, in vitro fertilization and intrauterine insemination (IUI) in human studies are inconclusive. Methods: This study is a retrospective review of 5,335 IUI [± ovarian stimulation (OS)] cycles from a large academic fertility center. Cycles were stratified based on the utilization of frozen (FROZEN, n = 1,871) instead of fresh ejaculated sperm (FRESH, n = 3,464). Main outcomes included human chorionic gonadotropin (HCG) positivity, clinical pregnancy (CP), and spontaneous abortion (SAB) rates. Secondary outcome was live birth (LB) rate. Odds ratios (OR) for all outcomes were calculated utilizing logistic regression and adjusted (adjOR) for maternal age, day-3 FSH, and OS regimen. Stratified analysis was performed based on OS subtype [gonadotropins; oral medications (OM): clomiphene citrate and letrozole; and unstimulated/natural]. Time to pregnancy and cumulative pregnancy rates were also calculated. Further subanalyses were performed limited to either the first cycle only or to the partner's sperm only, after excluding female factor infertility, and after stratification by female age (<30, 30-35, and >35 years old). Results: Overall, HCG positivity and CP were lower in the FROZEN compared to the FRESH group (12.2% vs. 15.6%, p < 0.001; 9.4% vs. 13.0%, p < 0.001, respectively), which persisted only among OM cycles after stratification (9.9% vs. 14.2% HCG positivity, p = 0.030; 8.1% vs. 11.8% CP, p = 0.041). Among all cycles, adjOR (95% CI) for HCG positivity and CP were 0.75 (0.56-1.02) and 0.77 (0.57-1.03), respectively, ref: FRESH. In OM cycles, adjOR (95% CI) for HCG positivity [0.55 (0.30-0.99)] and CP [0.49 (0.25-0.95), ref.: FRESH] favored the FRESH group but showed no differences among gonadotropin and natural cycles. SAB odds did not differ between groups among OM and natural cycles but were lower in the FROZEN group among gonadotropin cycles [adjOR (95% CI): 0.13 (0.02-0.98), ref.: FRESH]. There were no differences in CP and SAB in the performed subanalyses (limited to first cycles or partner's sperm only, after excluding female factors, or after stratification according to female age). Nevertheless, time to conception was slightly longer in the FROZEN compared to the FRESH group (3.84 vs. 2.58 cycles, p < 0.001). No significant differences were present in LB and cumulative pregnancy results, other than in the subgroup of natural cycles, where higher LB odds [adjOR (95% CI): 1.08 (1.05-1.12)] and higher cumulative pregnancy rate (34% vs. 15%, p = 0.002) were noted in the FROZEN compared to the FRESH group. Conclusion: Overall, clinical outcomes did not differ significantly between frozen and fresh sperm IUI cycles, although specific subgroups might benefit from fresh sperm utilization.

The impact of different sperm preparation methods on clinical pregnancy and live birth rates in intrauterine insemination cycles: a retrospective single-center cohort study.

OBJECTIVE: To assess the impact of 2 different sperm preparation methods, density gradient centrifugation and simple wash, on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles with and without ovulation induction. DESIGN: Retrospective single-center cohort study. SETTING: Academic fertility center. PATIENTS: In total, 1,503 women of all diagnoses sought IUI with fresh-ejaculated sperm. EXPOSURE: Cycles were divided into 2 groups on the basis of sperm preparation technique: density gradient centrifugation (n = 1,687, unexposed group) and simple wash (n = 1,691, exposed group). MAIN OUTCOME MEASURES: Primary outcome measures consisted of clinical pregnancy and live birth rates. Furthermore, adjusted odds ratios and 95% confidence intervals for each outcome were calculated and compared between the 2 sperm preparation groups. RESULTS: Odds ratios did not differ between density gradient centrifugation and simple wash groups for clinical pregnancy and live birth (1.10 [0.67-1.83] and 1.08 [0.85-1.37], respectively). Additionally, when cycles were stratified using ovulation induction rather than adjusted for, no differences in clinical pregnancy and live birth odds were noted between sperm preparation groups (gonadotropins: 0.93 [0.49-1.77] and 1.03 [0.75-1.41]; oral agents: 1.78 [0.68-4.61] and 1.05 [0.72-1.53]; unassisted: 0.08 [0.001-6.84] and 2.52 [0.63-10.00], respectively). Furthermore, no difference was seen in clinical pregnancy or live birth when cycles were stratified using sperm score or when the analysis was limited to first cycles only. CONCLUSION: Overall, no difference was noted in clinical pregnancy or live birth rates between patients who received simple wash vs. density gradient-prepared sperm, suggesting similar clinical efficacy between the 2 techniques for IUI. Because the simple wash technique is more time-efficient and cost-effective compared with the density gradient, adoption of this technique could lead to comparable clinical pregnancy and live birth rates for IUI cycles, although optimizing teamwork flow and coordination of care.

The impact of anti-Müllerian hormone on endometrial thickness in gonadotropin stimulation/intrauterine insemination cycles: is there an effect on pregnancy outcomes?

PURPOSE: To study the association, if any, between anti-Müllerian hormone (AMH) and pre-ovulatory endometrial thickness (ET) in gonadotropin/intrauterine insemination (IUI) cycles. METHODS: This retrospective cohort study included a total of 964 patients undergoing 1926 gonadotropin/IUI cycles at an academic fertility center. Primary outcome measure was the association between serum AMH and measured ET on the day of and the day before human chorionic gonadotropin hormone (hCG) ovulation trigger. The effect of a model combining AMH and ET on early pregnancy outcomes was a secondary measure. RESULTS: In 52.8% of cycles, ET was last assessed and recorded on the day of hCG administration, while in the remaining 47.2% on the day prior to trigger. In unadjusted regression models, AMH was weakly correlated with ET on hCG trigger day [bAMH (95%CI) = 0.032 (- 0.008, 0.070), p = 0.015]. When adjusting for potential confounders, the positive correlation became significant [0.051 (0.006, 0.102), p = 0.047]. Similar findings were observed when assessing the correlation between AMH and ET on the day prior to hCG trigger. ET was non-significantly associated with the odds of clinical pregnancy, when adjusting for potential confounders, except for when restricting the analysis to couples with idiopathic infertility [OR (95%CI), p-value: 0.787 (0.623, 0.993), 0.044]. CONCLUSION: Our findings support an effect of serum AMH on endometrial development in gonadotropin induced cycles, even when adjusting for the diagnosis of PCOS. ET was not associated with the odds of achieving a clinical pregnancy, except for couples with idiopathic infertility.

Optimizing pregnancy outcomes in intrauterine insemination cycles by stratifying pre-wash total motile count and patient-specific factors: a patient counseling tool.

PURPOSE: The purpose of this study is to clarify which pre-wash total motile count are associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) based on maternal age, AMH level, stimulation regimen, and infertility diagnosis. METHODS: This was a retrospective cohort study of first completed IUI cycles at two academic fertility centers from 5/2015 to 9/2019. Cycles were stratified by pre-wash TMC, maternal age, AMH level, stimulation regimen, and infertility diagnosis. The primary outcome was CPR and secondary outcomes were live birth and miscarriage. RESULTS: One thousand one hundred fifty-four cycles were analyzed. Of the 162 cycles that resulted in a CPR (14.0%), most had an insemination TMC > 20 million. Compared to TMC > 20 million, there was no difference in CPR or LBR for lower TMC categories, excluding the TMC < 2 million group, in which there were no pregnancies. When TMC was stratified by deciles, there was also no difference in CPR and LBR, including within the lowest decile (TMC 0.09-8.6 million). Younger age and higher ovarian reserve parameters were associated with higher pregnancy and LBR when stratified by TMC. There was no difference in pregnancy and LBR when considering different stimulation protocols. CONCLUSIONS: Our data suggest that pregnancy and LBR are equivalent above a TMC of 2 million. Data stratified by TMC and patient parameters can be used to counsel patients pursuing ART.

Association of preconception mixtures of phenol and phthalate metabolites with birthweight among subfertile couples.

Although parental preconception exposure to some phenols and phthalates have been associated with reduced birthweight, few studies have examined these chemicals as complex mixtures. Methods: We included 384 mothers and 211 fathers (203 couples) who gave birth to 384 singletons from a prospective cohort of couples seeking fertility evaluation. Urinary concentrations of bisphenol A (BPA), parabens, and 11 phthalate metabolites including those of di(2-ethylhexyl) phthalate (DEHP) were examined. Birthweight was abstracted from delivery records. We used principal component analysis and Bayesian Kernel Machine Regression (BKMR) to examine maternal and paternal preconception mixtures in relation to singleton birthweight. We also fit couple-based BKMR with hierarchical variable selection to assess couples' joint mixtures in relation to birthweight. Results: PC scores of maternal and paternal preconception low molecular weight phthalates factor, and paternal preconception DEHP-BPA factor were associated with reduced birthweight. In BKMR models, we found that maternal preconception monoethyl phthalate and BPA concentrations, and paternal preconception mono-n-butyl phthalate concentrations were inversely associated with birthweight when the remaining mixture components were held at their median concentrations. In couple-based BKMR models, paternal preconception biomarkers contributed more to couples' joint effect on birthweight compared with maternal preconception biomarkers. A decreasing trend of birthweight was observed across quantiles of maternal, paternal, and couples' total preconception mixture concentrations, respectively. Conclusions: Results from this preconception cohort of subfertile couples suggest a complex interplay between paternal and maternal preconception exposure to mixtures of nonpersistent chemicals, with both parental windows of exposure jointly contributing to reduced birthweight.

The effect of semen collection at home on intrauterine insemination outcomes.

BACKGROUND: The WHO 2010 guidelines recognize at-home semen collection as an acceptable alternative to standard collection at the clinic in "exceptional circumstances." There is lack of sufficient data to determine the need for revisiting these recommendations for treatment purposes. OBJECTIVES: To determine whether at-home semen collection has any effect on intrauterine insemination (IUI) cycle outcomes. MATERIALS AND METHODS: This is a retrospective cohort study of 729 IUI treatment cycles (382 patients) performed at an academic fertility center from September 19, 2019 to December 31, 2020. Semen collected at the "clinic" was used for 343 cycles before the Coronavirus Disease 2019 (COVID-19) pandemic (September 19, 2019 to March 21, 2020), and "at-home" collected specimens were used for 386 cycles following revised protocols with COVID-19-driven changes (May 30, 2020 to December 31, 2020). Logistic regression models were performed to evaluate the effect of "at-home" semen collection on achieving a positive pregnancy test (PPT) and a clinical pregnancy (CP). RESULTS: Male and female partners' age, ovarian reserve biomarkers, and stimulation regimens used were similar in the "clinic" and "at-home" groups. In unadjusted models, "at-home" collection had no significant effect on the odds for a PPT [OR (95%CI): 0.733 (0.503-1.069)] or CP [0.816 (0.543-1.226)]. These results persisted even when adjusting for maternal age and anti-Müllerian hormone: PPT [0.739 (0.505-1.081)] and CP [0.826 (0.547-1.248)]. Of the semen analysis parameters under evaluation, only motility appeared to significantly impact the odds of achieving a PPT [1.014 (1.004-1.025)] and a CP [1.017 (1.006-1.029)]. This effect was slightly attenuated for samples collected "at-home" [1.012 (0.997-1.027) and 1.015 (0.999-1.031), respectively, for PPT and CP]. DISCUSSION: This study adds important information to the limited literature regarding the effect of at-home semen collection on IUI outcomes. Under adequate protocols, at-home semen collection should be considered a safe alternative. Additional research is needed to optimize such protocols. CONCLUSION: Our data suggest that at-home semen collection does not negatively impact IUI pregnancy outcomes.

Phthalate and DINCH urinary concentrations across pregnancy and risk of preterm birth.

Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of ∑DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean ∑DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation.

Mutual Preservation: A Review of Interactions Between Cervicovaginal Mucus and Microbiota.

At mucosal surfaces throughout the body mucus and mucins regulate interactions between epithelia and both commensal and pathogenic bacteria. Although the microbes in the female genital tract have been linked to multiple reproductive health outcomes, the role of cervicovaginal mucus in regulating genital tract microbes is largely unexplored. Mucus-microbe interactions could support the predominance of specific bacterial species and, conversely, commensal bacteria can influence mucus properties and its influence on reproductive health. Herein, we discuss the current evidence for both synergistic and antagonistic interactions between cervicovaginal mucus and the female genital tract microbiome, and how an improved understanding of these relationships could significantly improve women's health.

Response to ovulation induction treatments in women with polycystic ovary syndrome as a function of serum anti-Müllerian hormone levels.

PURPOSE: To assess whether anti-Müllerian hormone (AMH) can predict response to ovulation induction (OI) with clomiphene citrate (CC), letrozole (LET), or follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS) undergoing OI/intrauterine inseminations (IUI). METHODS: A total of 738 OI/IUI cycles from 242 patients at an academic center were stratified in three groups by medication: CC (n = 295), LET (n = 180), and FSH (n = 263), in a retrospective fashion. Ovarian response to treatment (RT, development of at least one dominant follicle) was assessed using mixed effects logistic regression models. RESULTS: Overall, RT cycles had lower AMH levels compared to no-RT cycles (p < 0.001). This finding persisted when analysis was limited to oral agents but attenuated in FSH cycles. For CC and LET cycles, the predicted probability (PProb) for RT decreased as AMH levels increased (PProb (95%CI): 97% (93-100), 79% (70-88), and 75% (61-89); 85% (78-93), 75% (67-83), and 73% (63-86) for AMH pct.: ≤ 25th, ≥ 50th, and ≥ 75th, for CC and LET, respectively)). However, RT was noted in 98.5% of FSH/IUI cycles regardless of AMH. For CC cycles, those with AMH ≥ 75th pct. had lower odds for RT over cycles with AMH < 75th pct. (OR 0.2, 95%CI 0.04-0.8, p = 0.02). Similarly, lower odds for RT were observed in LET cycles with AMH ≥ 75th pct. (0.6, 0.3-1.4, p = 0.25). CONCLUSION: In PCOS, increasing serum AMH levels are associated with lower probability of RT to oral agents. Our findings constitute a valuable tool for the clinician when counseling PCOS patients and designing a personalized ovulation induction treatment strategy.

Pretreatment antimüllerian hormone levels and outcomes of ovarian stimulation with gonadotropins/intrauterine insemination cycles.

OBJECTIVE: To evaluate the association, if any, between serum antimüllerian hormone (AMH) levels and probability of clinical pregnancy and spontaneous abortion (SAB) in the infertility setting. DESIGN: Retrospective cohort study. SETTING: Academic fertility center. PATIENT(S): A total of 1,861 gonadotropin stimulation/intrauterine insemination cycles stratified by AMH levels into 3 groups: Low, <25th percentile (<0.7 ng/mL); Middle, ≥25th and <75th percentile (0.7-4.4 ng/mL); and High, ≥75th percentile (≥4.5 ng/mL). INTERVENTION(S): Intrauterine insemination after stimulation with gonadotropins. MAIN OUTCOME MEASURE(S): Cumulative probability of clinical pregnancy over a maximum of 3 and/or 6 cycles and SAB incidence risk rate (IRR). The Kaplan-Meier failure function (log rank test), Cox proportional hazards models, and multilevel mixed-effects Poisson regression models were performed to compare outcomes among the AMH groups. RESULT(S): Overall, in both unadjusted and adjusted models, the probability of achieving a clinical pregnancy was higher in the Middle and High AMH groups compared with that in the Low AMH group, both over 3 (hazard ratios [95% confidence interval], 1.55 [1.05-2.29] and 1.85 [1.22-2.81], respectively) and 6 (1.71 [1.17-2.48] and 2.12 [1.42-3.16], respectively) cycles. In the unadjusted models, the SAB IRR was higher among the Low AMH group (IRR [95% confidence interval], 2.17 (1.11-4.24]), with the relationship persisting after adjusting for age (1.83 [0.93-3.60]). When the SAB IRR were calculated separately for the subpopulations with and without polycystic ovary syndrome, a similar relationship was noted among the latter in the unadjusted (1.94 [0.97-3.88]) and adjusted (1.74 [0.86-3.49]) analyses. CONCLUSION(S): In women undergoing gonadotropin stimulation/intrauterine insemination, AMH appears to affect the probability of achieving a clinical pregnancy. A possible negative impact, independent of age, on the risk of SAB was also suggested.

The effect of semen collection location and time to processing on sperm parameters and early IVF/ICSI outcomes.

PURPOSE: We aimed to assess whether home collection and increased time to semen processing are associated with altered sperm parameters, fertilization rates (FR), day 5 usable quality blastocyst development rates (D5-UQBR), or pregnancy rates (PR) in patients undergoing IVF/ICSI. METHODS: This was a retrospective cohort study of patients undergoing IVF/ICSI before the coronavirus disease 2019 (COVID-19) pandemic ("clinic" collection, n = 119) and after COVID-19 ("home" collection, n = 125) at an academic fertility practice. Home collection occurred within 2 h of semen processing. Patient sperm parameters, FR (#2PN/MII), D5-UQBR (# transferable and freezable quality blastocysts/# 2PN), and PR in fresh transfer cycles were compared between clinic and home groups with t-tests. The association between time to processing on outcomes was assessed with regression modeling, controlling for potential confounders. RESULTS: Mean male age was 37.9 years in the clinic group and 37.2 years in the home group (p = 0.380). On average, men were abstinent for 3.0 days (SD 1.7) in the clinic group and 4.1 days (SD 5.4) in the home group (p = 0.028). Mean time to semen processing was 35.7 min (SD 9.4) in the clinic group and 82.6 min (SD 33.8) in the home group (p < 0.001). There was no association between collection location and increased time to processing on sperm motility, total motile count, FR, D5-UQBR, or PR. CONCLUSIONS: Our data suggest that increased time to processing up to 2 h with home semen collection does not negatively impact sperm parameters or early IVF/ICSI outcomes.

Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birth.

BACKGROUND: Parental preconception exposure to select phenols and phthalates was previously associated with increased risk of preterm birth in single chemical analyses. However, the joint effect of phenol and phthalate mixtures on preterm birth is unknown. METHODS: We included 384 female and 211 male (203 couples) participants seeking infertility treatment in the Environment and Reproductive Health (EARTH) Study who gave birth to 384 singleton infants between 2005 and 2018. Mean preconception urinary concentrations of bisphenol A (BPA), parabens, and eleven phthalate biomarkers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal component analysis (PCA) with log-Poisson regression and Probit Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection to examine maternal and paternal phenol and phthalate mixtures in relation to preterm birth. Couple-based BKMR model was fit to assess couples' joint mixtures in relation to preterm birth. RESULTS: PCA identified the same four factors for maternal and paternal preconception mixtures. Each unit increase in PCA scores of maternal (adjusted Risk Ratio (aRR): 1.36, 95%CI: 1.00, 1.84) and paternal (aRR: 1.47, 95%CI: 0.90, 2.42) preconception DEHP-BPA factor was positively associated with preterm birth. Maternal and paternal BKMR models consistently presented the DEHP-BPA factor with the highest group Posterior Inclusion Probability (PIP). BKMR models further showed that maternal preconception BPA and mono(2-ethyl-5-hydroxyhexyl) phthalate, and paternal preconception mono(2-ethylhexyl) phthalate were positively associated with preterm birth when the remaining mixture components were held at their median concentrations. Couple-based BKMR models showed a similar relative contribution of paternal (PIP: 61%) and maternal (PIP: 77%) preconception mixtures on preterm birth. We found a positive joint effect on preterm birth across increasing quantiles of couples' total mixture concentrations. CONCLUSION: In this prospective cohort of subfertile couples, maternal BPA and DEHP, and paternal DEHP exposure before conception were positively associated with preterm birth. Both parental windows jointly contributed to the outcome. These results suggest that preterm birth may be a couple-based pregnancy outcome.

A patient-specific model combining antimüllerian hormone and body mass index as a predictor of polycystic ovary syndrome and other oligo-anovulation disorders.

OBJECTIVE: To determine whether a patient-specific predictive model combining antimüllerian hormone (AMH) levels and body mass index (BMI) can aid in the diagnosis of polycystic ovary syndrome (PCOS) and other ovulatory dysfunction disorders (OVDYS) among infertile women. DESIGN: Retrospective cohort study. SETTING: Academic fertility center. PATIENT(S): One thousand and ten infertile women undergoing 3,160 intrauterine insemination (IUI) cycles, stratified by diagnosis in three groups: PCOS, OVDYS, and other etiologies. INTERVENTION(S): Ovulation induction followed by IUI or ultrasound-monitored natural cycles. MAIN OUTCOME MEASURE(S): The probability of either PCOS or OVDYS diagnosis based on AMH levels alone and a patient-specific predictive model that combines serum AMH and patient's BMI. RESULT(S): Median and interquartile range (IQR) for the serum AMH levels (ng/mL) were the highest in women with PCOS, and lowest in those with other infertility causes. Overall, for every 1 ng/mL increase in AMH, the odds of PCOS and OVDYS versus other causes increased by 55% and 24%, respectively. Postestimation from multivariate logistic regression models showed that PCOS diagnosis can be predicted with lower AMH values in women with a higher BMI compared with the AMH values predicting PCOS in normal-weight or underweight patients. The receiver operating characteristic curves reinforced these findings, and the best cutoffs for PCOS diagnosis were 7.5, 4.4, and 4.1 ng/mL for women belonging to the BMI groups 18.5-24.9, 25.0-29.9, and ≥30.0 kg/m2, respectively. CONCLUSION(S): Taking into account AMH and BMI, we developed a model that predicts the probability of an oligo-anovulation diagnosis, thus facilitating patient-specific counseling in the infertility setting.

Understanding the potential of lactobacilli in recurrent UTI prevention.

Urinary tract infections (UTIs) are one of the most common infections in women. The only proven preventive strategy for recurrent UTIs is prophylactic antibiotics. Given growing antibiotic resistance, the use of probiotics has been proposed as an alternative to antibiotics. Herein, we discuss the current evidence to support the possibility that exogenous lactobacilli may limit the pathogenicity of uropathogens such as E. coli. Probiotics appear to have a significant potential in prevention of recurrent UTI, however, additional data are needed to understand how they can be effectively used in clinical practice.

Could Mismatch Repair Status Serve as a Biomarker for Immunotherapy in Endometrial Carcinoma?

AIM: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas. MATERIALS AND METHODS: The expression of MMR protein PD-L1 and CD8+ cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters. RESULTS: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8+ cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas non-endometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1+/CD8high status (p=0.006), whilst MMR proficiency was associated with PD-L1-/CD8low status. In MMR-proficient tumors, high CD8+ cell infiltration alone and combined with PD-L1- status was associated with better progression-free survival (p=0.013 and p=0.04, respectively). CONCLUSION: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.

Toll-Like Receptors -2, -3, -4 and -7 Expression Patterns in the Liver of a CLP-Induced Sepsis Mouse Model.

Objective: To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. Materials and methods: For this study seventy-two C57BL/6J mice were utilized. Sepsis was induced by cecal ligation and puncture (CLP) in the mice of the three septic (S) groups (euthanized at 24 hours, 48 hours and 72 hours). Sham (laparotomy)- operated mice constituted the control (C) groups (euthanized at 24, 48 and 72 hours). Blood samples were drawn and liver tissues were extracted and examined histologically. The expression of TLRs 2, 3, 4 and 7 was assessed via immunohistochemistry (IHC) and qrt-PCR (quantitative- Polymerase Chain Reaction). Results: Liver function tests were elevated in all S-groups in contrast to their time-equivalent control groups (S24 versus C24, S48 versus C48 and S72 versus C72) (p < 0.05). Liver histology displayed progressive deterioration in the septic groups. IHC and qrt-PCR both showed an increased expression of all TLRs in the septic mice in comparison to their analogous control ones (p < 0.05). Analysis of livers and intestines of the septic animals proved that all TLRs were significantly expressed in higher levels in the intestinal tissues at 24h and 48h (p < 0.05) except for TLR 3 in S48 (p > 0.05); whereas at 72 hours only TLR 4 levels were significantly elevated in the intestine (p < 0.05). Conclusion: TLRs seem to be expressed in significant levels in the livers of septic rodents, indicating that they have a possible role in the pathophysiology of liver damage in septic conditions.

Mismatch repair status in high-grade endometrial carcinomas of endometrioid and non-endometrioid type.

PURPOSE: To evaluate mismatch repair (MMR) status in a series of high-grade endometrial carcinomas and correlate it with several clinicopathological characteristics and with survival. METHODS: One hundred and one patients with high-grade endometrial carcinoma, both of endometrioid and of non-endometrioid type were included in the study. The expression of MLH1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. RESULTS: In our cohort, 41 women had an endometrioid and 60 women a non-endometrioid carcinoma. Endometrioid histotype was statistically more frequent in deficient MMR (dMMR) tumors (73.3%), while non-endometrioid carcinomas in proficient (pMMR) cases (73.8%) (p<0.001). When analyzing the group of endometrioid and non-endometrioid carcinomas separately, only dMMR endometrioid cancers were found to be statistically related to deep myometrial invasion, lymph-node metastases and advanced stage (p=0.035, p=0.011 and p=0.028, respectively). Univariate and multivariate analysis revealed no relation between MMR status and progression-free survival (PFS) or overall survival (OS). Adjuvant treatment was not found to influence the course of the disease. When MMR proteins were studied separately, MLH1/PMS2 loss was related to deep myometrial invasion (p=0.019 and p=0.036, respectively) and MSH6 loss to lymph-node metastases (p=0.04). CONCLUSIONS: In our group of high-grade endometrial carcinomas, MMR deficiency was statistically more frequent in endometrioid than in non-endometrioid cancers. Furthermore, only dMMR endometrioid type grade 3 carcinomas were found to be related with features indicative of aggressive behavior. Considering some unique relation of each MMR protein with distinct clinicopathological features, the assessment of all four proteins is proposed.

The impact of programmed cell death-ligand 1 (PD-L1) and CD8 expression in grade 3 endometrial carcinomas.

BACKGROUND: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) and CD8 in high-grade endometrial carcinomas and relate it to several clinicopathological parameters. METHODS: One hundred and one (101) patients with high-grade endometrial carcinomas who were completely surgically staged were included in this study. PD-L1 and CD8 + expression was evaluated by immunohistochemistry. RESULTS: In our cohort, 47 women (46.5%) had endometrioid carcinomas and 54 patients (53.5%) were diagnosed with non-endometrioid cancers. In endometrioid carcinomas, there was a significantly higher rate of positivity for PD-L1 expression (p = 0.042) and of intraepithelial CD8 + cell counts (p = 0.004) as opposed to non-endometrioid cancers. There were no significant relationships with any of the other clinicopathological features under study. Univariate and multivariate analysis revealed that only high intraepithelial CD8 + counts (p = 0.01) was associated with longer progression-free survival. Tumors positive for PD-L1 and high intraepithelial CD8 expression were mainly of endometrioid histology, whilst PD-L1-positive/CD8 low and PD-L1-negative/CD8 low tumors were mostly non-endometrioid carcinomas (p = 0.01). PD-L1 negative/CD8 high tumors had the longest progression-free survival (p = 0.032). CONCLUSIONS: In grade 3 endometrial carcinomas, both of endometrioid and non-endometrioid type, high intraepithelial CD8 + counts represent an independent favorable prognostic factor and when related to PD-L1-negative tumors, a longer progression-free survival can be predicted. Immunotherapy could probably be considered for PD-L1-positive/CD8 + high tumors, which were mostly of endometrioid histology.

Increased expression of Toll-like receptors 2, 3, 4 and 7 mRNA in the kidney and intestine of a septic mouse model.

Toll-like receptors (TLRs) are the key regulators of innate and adaptive immunity and are highly expressed during sepsis. Thus, studying the expression of TLRs in an animal septic model might indicate their possible association with acute kidney injury in sepsis. Seventy-two male C57BL/6J mice were used for this study. Randomly, these animals were divided into 6 groups (N = 12/group): 3 control and 3 septic groups depending on the euthanasia time (24 h, 48 h, 72 h). Septic groups underwent cecal ligation and puncture (CLP) to induce peritonitis, while control groups had a sham operation. Hematological tests were performed in serum for immune biomarkers; immunohistochemistry, morphometry and qRT-PCR analysis were used on both kidney and intestine tissues to evaluate the expression of TLR 2, 3, 4 and 7 in a septic process. At the end of each experimental period, we found that TLRs 2, 3, 4 and 7 were expressed in both tissues but there were differences between those at various time points. Also, we found that mRNA levels were significantly higher in qRT-PCR evaluation in septic groups than control groups in both kidney and intestinal tissues (p < 0.05); showing a steady increase in the septic groups as the time to euthanasia was prolonged (p < 0.05). Overall, our study provides a suggestion that TLRs 2, 3, 4 and 7 are highly expressed in the kidneys of septic mice and especially that these TLRs are sensitive and specific markers for sepsis. Finally, our study supports the diagnostic importance of TLRs in AKI and provides an insight on the contribution of septic mice models in the study of multi organ dysfunction syndrome in general.