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Reproductive Biomedicine Online Apr 2024This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF,... (Review)
Review
This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality.
PubMed: 38943812
DOI: 10.1016/j.rbmo.2024.104075 -
Reproductive Biomedicine Online May 2024The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire...
The pathophysiology of endometriosis remains unclear. Retrograde menstruation could be a phenomenon that initiates the process, but it may not explain the entire pathophysiology of endometriosis. Current evidence suggests that endometriosis is a type of chronic inflammatory disease. Many conditions that affect the vascular endothelium, including atherosclerosis, cardiovascular disease and pre-eclampsia, have been shown to be associated with endometriosis. Evidence to date suggests a complex interaction in endometriosis between angiogenesis, hormones and immunological changes stemming from chronic inflammation, with the inflammatory cells releasing cytokines and chemokines including tumour necrosis factor-α (TNF-α). Indeed, TNF-α is considered to be one of the possible markers of endometriosis in the blood, endometrium or menstrual blood. We emphasize the importance of pursuing research for novel and safer anti-inflammatory and immunomodulatory drugs that can be used by patients with endometriosis on a long-term basis.
PubMed: 38943810
DOI: 10.1016/j.rbmo.2024.104292 -
ESMO Open Jun 2024The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone...
Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.
BACKGROUND
The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT.
METHODS
We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples.
RESULTS
The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS.
CONCLUSIONS
HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.
PubMed: 38943737
DOI: 10.1016/j.esmoop.2024.103619 -
Gynecologic Oncology Jun 2024Advanced epithelial ovarian cancer (OC) patients often present with malnutrition; however, the ideal nutritional evaluation tool is unclear. We aimed to evaluate the...
BACKGROUND
Advanced epithelial ovarian cancer (OC) patients often present with malnutrition; however, the ideal nutritional evaluation tool is unclear. We aimed to evaluate the role of preoperative albumin, Prognostic Nutritional Index [PNI], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR] as independent predictors of severe postoperative complications and 90-day mortality in OC patients who underwent primary cytoreductive surgery to identify the ideal tool.
METHODS
OC patients who underwent surgery at Mayo Clinic (2003-2018) were included; biomarkers were retrospectively retrieved and established cut-offs were utilized. Outcomes included severe complications (Accordion grade ≥ 3) and 90-day mortality. Univariate and multivariable logistic regression models were performed. Biomarkers were evaluated in separate models adjusted for age and American Society of Anesthesiologists (ASA) score for 90-day mortality, and adjusted for age, ASA score, stage, and surgical complexity for severe complications.
RESULTS
Albumin <3.5 g/dL, PNI < 45, NLR > 6 and PLR ≥ 200 were univariately associated with 90-day mortality (all p < 0.05) in 627 patients that met inclusion criteria. Each marker remained significant in adjusted models with albumin having the highest OR: 6.04 [95% CI:2.80-13.03] and AUC (0.83). Univariately, PNI <45, NLR >6, and PLR ≥200 were significant predictors of severe complications(all p < 0.05), however failed to reach significance in adjusted models. Albumin was not associated with severe complications.
CONCLUSION
All biomarkers were associated with 90-day mortality in adjusted models, with albumin being the easiest predictor to attain clinically; none with severe complications. Future research should focus less on methods of nutritional assessment and more on strategies to improve nutrition during OC tumor-directed therapy.
PubMed: 38943693
DOI: 10.1016/j.ygyno.2024.06.021 -
Gynecologic Oncology Jun 2024Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has...
INTRODUCTION
Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients.
MATERIALS & METHODS
We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression.
RESULTS
We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival.
DISCUSSION
Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.
PubMed: 38943692
DOI: 10.1016/j.ygyno.2024.06.018 -
Gynecologic Oncology Jun 2024In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance...
OBJECTIVES
In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC.
METHODS
In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors.
RESULTS
This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8 cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR.
CONCLUSIONS
Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
PubMed: 38943691
DOI: 10.1016/j.ygyno.2024.06.017 -
AIDS Care Jun 2024Cisgender women and transgender men are less likely to be assessed for PrEP eligibility, prescribed PrEP, or retained in PrEP care. Thus, this pilot PrEP educational...
A mixed-methods evaluation of an HIV pre-exposure prophylaxis educational intervention for healthcare providers in a NYC safety-net hospital-based obstetrics and gynecology clinic.
Cisgender women and transgender men are less likely to be assessed for PrEP eligibility, prescribed PrEP, or retained in PrEP care. Thus, this pilot PrEP educational intervention was tailored for healthcare providers (HCPs) in obstetrics/gynecology who provide care to cisgender women and transgender men in an academically-affiliated, public hospital women's health clinic. The three-lecture educational curriculum designed for HCPs focused on PrEP eligibility and counseling, formulations and adherence, and prescription and payment assistance programs. Pre- and post-intervention surveys assessed HCP knowledge and barriers to PrEP counseling and prescription. Among = 49 participants (mean age = 32.8 years; 85.7% cisgender women, mean years practicing = 4.2 years) pre-intervention, 8.7% had prior PrEP training and 61.2% felt very/somewhat uncomfortable prescribing PrEP. Post-intervention, knowledge of PrEP contraindications, eligibility, follow-up care, and assistance programs all increased. HCPs identified key barriers to PrEP care including lack of a dedicated PrEP navigator, culturally and linguistically appropriate patient materials on PrEP resources/costs, and PrEP-related content integrated into EHRs. Ongoing PrEP educational sessions can provide opportunities to practice PrEP counseling, including information on financial assistance. At the institutional level, incorporating PrEP screening in routine clinical practice via EMR prompts, facilitating PrEP medication monitoring, and enhancing telehealth for follow-up care could enhance PrEP prescription.
PubMed: 38943674
DOI: 10.1080/09540121.2024.2364218 -
Cancer Jun 2024Telehealth technologies offer efficient ways to deliver health-related social needs (HRSN) screening in cancer care, but these methods may not reach all populations. The...
BACKGROUND
Telehealth technologies offer efficient ways to deliver health-related social needs (HRSN) screening in cancer care, but these methods may not reach all populations. The authors examined patient characteristics associated with using an online patient portal (OPP) to complete HRSN screening as part of gynecologic cancer care.
METHODS
From June 2021 to June 2023, patients in a gynecologic oncology clinic completed validated HRSN screening questions either (1) using the OPP (independently before the visit) or (2) in person (verbally administered by clinic staff). The authors examined the prevalence of HRSN according to activated OPP status and, in a restricted subgroup, used stepwise multivariate Poisson regression to identify associations between patient and visit characteristics and using the OPP.
RESULTS
Of 1616 patients, 87.4% (n = 1413) had an activated OPP. Patients with inactive OPPs (vs. activated OPPs) more frequently reported two or more needs (10% vs 5%; p < .01). Of 986 patients in the restricted cohort, 52% used the OPP to complete screening. The final multivariable model indicated that patients were less likely to use the OPP if they were Black (vs. White; adjusted relative risk [aRR], 0.70; 95% confidence interval [CI], 0.59-0.83); not employed (vs. employed; aRR, 0.81; 95% CI, 0.68-0.97), or had low measures of OPP engagement (aRR, 0.80; 95% CI, 0.68-0.92). New versus established patients were 21% more likely to use the OPP (aRR, 1.21; 95% CI, 1.06-1.38).
CONCLUSIONS
Differential use of the OPP suggested that over-reliance on digital technologies could limit the ability to reach those populations that have social factors already associated with cancer outcome disparities. Cancer centers should consider using multiple delivery methods for HRSN screening to maximize reach to all populations.
PubMed: 38943672
DOI: 10.1002/cncr.35376 -
The Journal of Clinical Endocrinology... Jun 2024The study aimed to explore the causal effect of body mass index (BMI) on polycystic ovarian syndrome (PCOS).
OBJECTIVE
The study aimed to explore the causal effect of body mass index (BMI) on polycystic ovarian syndrome (PCOS).
METHODS
Genome-wide association data for BMI and PCOS were sourced from the Mendelian randomization (MR) base platform. Significantly associated single nucleotide polymorphisms (SNPs) for BMI served as instrumental variables in bidirectional two-sample MR analyses to investigate the causal relationship between BMI and PCOS. Analytical techniques utilized encompassed the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression.
RESULTS
We identified 427 SNPs significantly associated with BMI (P < 5 × 10-8; linkage disequilibrium r2 < 0.001). Various methods consistently revealed a positive association between BMI and PCOS (IVW: odds ratio (OR) 2.027, 95% confidence interval (CI) 1.599-2.596; weighted median estimator: OR 2.368, 95% CI 1.653-3.392; MR-Egger Method: OR 3.610, 95% CI 1.795-7.263), indicating that higher BMI correlates with an increased risk of PCOS. Additionally, we observed a causal effect of genetic predisposition to PCOS on BMI (IVW: OR 1.020, 95% CI (1.019-1.022); weighted median estimator: OR 1.017, 95% CI (1.015-1.019); MR-Egger Method: OR 1.000, 95% CI (0.995-1.005)).
CONCLUSION
The MR analysis furnished compelling evidence suggesting a causal relationship between elevated BMI and the risk of PCOS, as well as indicating that the severity of PCOS may contribute to elevated BMI levels.
PubMed: 38943662
DOI: 10.1210/clinem/dgae446 -
Journal of Evidence-based Medicine Jun 2024
Topics: Randomized Controlled Trials as Topic; Humans; Placebos
PubMed: 38943606
DOI: 10.1111/jebm.12625