Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer.

PURPOSE OF REVIEW: In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. RECENT FINDINGS: There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.

Vigorous vs. moderate exercise to improve glucose metabolism in inactive women with polycystic ovary syndrome and insulin resistance: a pilot randomized controlled trial of two home-based exercise routines.

Objective: To study the impact of vigorous vs. moderate exercise on metabolic parameters in polycystic ovary syndrome (PCOS). Design: Randomized controlled trial. Setting: Unsupervised home-based exercise program. Patients: Patients with PCOS on the basis of the Rotterdam criteria with insulin resistance. Interventions: Participants were block randomized to a home-based exercise program of 75 minutes of vigorous exercise or 150 minutes of moderate exercise per week, for 8 weeks total. Main Outcome Measures: Changes in glucose, insulin, and insulin resistance. Results: In total, 36 participants were randomized, of whom 20 completed the study. The percentage changes from baseline at 4 and 8 weeks for fasting glucose, insulin, and homeostatic model assessment for insulin resistance did not significantly differ between the groups, except for the change in the 8-week glucose level, which was more favorable in the moderate arm (8.06% [standard deviation, 6.44%] in the vigorous group compared with -0.32% [standard deviation, 4.91%] in the moderate group). The absolute values of the main outcomes (fasting glucose, insulin, and homeostatic model assessment for insulin resistance) at baseline and 4 and 8 weeks did not significantly differ between trial arms. When assessing the change from baseline at 4 and 8 weeks, overall and within each trial arm, only the 8-week fasting glucose level was significantly greater than the baseline value in the vigorous arm (93.5 [95% confidence interval, 88.7-98.3] vs. 86.8 [95% confidence interval, 81.1-92.4]). Conclusions: Unsupervised short-term exercise programs may not achieve significant metabolic improvements in patients with PCOS, regardless of vigorous vs. moderate intensity. Future studies should investigate this question in larger sample sizes and longer or structured exercise programs. Clinical Trial Registration Number: ClinicalTrials.gov identifier, NCT02303470.

Hierarchical Style-Aware Domain Generalization for Remote Physiological Measurement.

The utilization of remote photoplethysmography (rPPG) technology has gained attention in recent years due to its ability to extract blood volume pulse (BVP) from facial videos, making it accessible for various applications such as health monitoring and emotional analysis. However, the BVP signal is susceptible to complex environmental changes or individual differences, causing existing methods to struggle in generalizing for unseen domains. This article addresses the domain shift problem in rPPG measurement and shows that most domain generalization methods fail to work well in this problem due to ambiguous instance-specific differences. To address this, the article proposes a novel approach called Hierarchical Style-aware Representation Disentangling (HSRD). HSRD improves generalization capacity by separating domain-invariant and instance-specific feature space during training, which increases the robustness of out-of-distribution samples during inference. This work presents state-of-the-art performance against several methods in both cross and intra-dataset settings.

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

Racial and ethnic differences in self-reported satisfaction with fertility clinics and doctors.

OBJECTIVE: To investigate if differences in self-reported satisfaction with fertility clinics and doctors differ by race/ethnicity. STUDY DESIGN: We used cross-sectional survey data from FertilityIQ online questionnaires completed by patients receiving US. fertility care from July 2015 to December 2020. Univariate and multivariate logistic and linear regression analyses were performed to assess association of race/ethnicity on patient-reported clinic and physician satisfaction. RESULTS: Our total sample size included 21,472 unique survey responses (15,986 Caucasian, 1856 Black, 1780 LatinX, 771 East Asian, 619 South Asian, 273 Middle Eastern, 187 Native American self-reported). When adjusting for potential confounders (demographic and patient satisfaction), we found that Black patients rated their doctors more highly (odds ratio (OR) 1.30, 95% confidence interval (CI) 1.04-1.62 p = 0.022 logistic and Coefficient 0.082, 95% CI 0.013-0.15 p = 0.02 linear), while other ethnic groups did not show significant differences compared to Caucasian patients. East Asians had borderline lower satisfaction with clinic satisfaction in logistic regression (OR 0.74 95% CI 0.55-1.00 p = 0.05), while significant differences were not found for other ethnic groups for clinic satisfaction. CONCLUSIONS: In summary, some but not all minority groups differed in their self-reported perception of satisfaction with fertility clinic and doctors compared to Caucasian patients. Cultural differences towards surveys may contribute to some of these findings, and satisfaction by racial/ethnic group may also be modified by results of care.

Serum Ribonucleotide Reductase Subunit M2 in Patients with Chronic Liver Diseases and Hepatocellular Carcinoma.

BACKGROUND: Ribonucleotide reductase subunit M2 (RRM2) plays a key role in cell and hepatitis B virus (HBV) replication. Nevertheless, its clinical implications for managing liver diseases have been inadequately studied. METHODS: A total of 412 participants were enrolled, including 60 healthy control individuals, 55 patients with chronic hepatitis B (CHB), 173 patients with cirrhosis, and 124 patients with hepatocellular carcinoma (HCC). Serum RRM2 was measured via ELISA. RESULTS: The level of serum RRM2 in patients with CHB, cirrhosis, and HCC was higher than that in healthy controls (P < .05). A large difference in serum RRM2 was found between HBV-related and non-HBV-related patients in the cirrhosis group (P < .001), compared with the difference between HBV-related HCC and non-HBV-related HCC (P = .86). In the HBV-related cirrhosis group, the serum RRM2 level showed significant positive correlations with HBV DNA, hepatitis B surface antigen, hepatitis B e antigen, Child-Pugh scores, and MELD scores and played a strong role in diagnosing HBV-related cirrhosis in CHB, compared with fibrosis-4 score and aspartate aminotransferase-to-platelet ratio index. CONCLUSIONS: Serum RRM2 is a reliable biomarker for accurate HBV-related cirrhosis diagnosis and evaluation. Also, serum RRM2 could reflect the expression state of HBV replication in patients with HBV-related cirrhosis.

Hormone concentrations of dominant follicles in the TALES randomized controlled trial comparing letrozole with tamoxifen.

BACKGROUND: In this secondary analysis of the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) trial, we aimed to investigate if concurrent administration of letrozole vs. tamoxifen vs. no added treatment affects hormonal composition and size of stimulated ovarian follicles. METHODS: TALES is a randomized controlled trial of IVF stimulation for estrogen receptor (ER)-positive breast cancer patients stimulated with gonadotropins and administered concurrent tamoxifen 20 mg or letrozole 5 mg. We analyzed estradiol (E2), testosterone (T), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH). We used ANOVA/Kruskal-Wallis, logistic, and linear regression models to examine differences in follicular hormone levels, size, and mature oocyte yield between trial arm. RESULTS: We included data from total 246 follicles (94 letrozole, 82 tamoxifen, and 70 control) from 123 unique participants. E2 was lower (letrozole 187.4, tamoxifen 1026.0, control 821.5 ng/mL, p < 0.01) and T was higher (letrozole 2489, tamoxifen 571, and control 504 ng/mL, p < 0.03) in the letrozole group compared to tamoxifen and control groups, while other hormone levels and follicle size were similar across groups. There were no significant differences in hormone concentrations within the follicle between tamoxifen and control arms. On multivariate logistic regression, there was no significant association of mature oocyte yield by follicle size, hormone levels, or trial arm. CONCLUSIONS: Concurrent administration of letrozole with gonadotropins affects follicular E2 and T concentrations compared to tamoxifen/control. Tamoxifen was not associated with any differences in hormone concentrations within the follicle. Mature oocyte yield was similar across groups.

Breast cancer grade and stage do not affect fertility preservation outcomes.

PURPOSE: To investigate if breast cancer stage and grade affect fertility preservation outcomes. METHODS: We performed a retrospective cohort study that included premenopausal women with breast cancer undergoing fertility preservation diagnosed between January 2011 and January 2019. The primary outcome measure was the number of mature oocytes (MII) per antral follicle count (AFC). Secondary outcome measures included total oocytes retrieved, total mature oocytes retrieved, and greater than 10 mature oocytes preserved. Univariate and multivariate models were used to assess the association of low vs. high stage (low stage I-II and high stage III-IV) and grade I vs. grade II/III with each outcome, with adjustment for confounders. RESULTS: A total of 267 premenopausal breast cancer patients undergoing fertility preservation were included in our study, with the majority presenting with low stage (N = 215, 80.5%), grade II/III (N = 235, 88.1%) disease. Baseline AFC, total gonadotropin dose, days of stimulation, and follicles [Formula: see text] 13 mm on the day of trigger did not differ by stage or grade. After adjusting for age, BMI, and baseline AFC, we found that the mean MII per AFC did not differ by stage (1.0 vs. 1.1, P = 0.3) or grade (1.0 vs. 1.0, P = 0.92). Similarly, total oocytes retrieved, total MII retrieved, and percentage of patients who were able to preserve greater than 10 MII did not differ by breast cancer stage or grade (all P > 0.2). CONCLUSION: Breast cancer grade and stage do not impact ovarian stimulation or fertility preservation outcome.

Cross-Regional Customized Bus Route Planning Considering Staggered Commuting During the COVID-19.

In order to solve the problem of cross-regional customized bus (CB) route planning during the COVID-19, we develop a CB route planning method based on an improved Q-learning algorithm. First, we design a sub-regional route planning approach considering commuters' time windows of pick-up stops and drop-off stops. Second, for the CB route with the optimal social total travel cost, we improve the traditional Q-learning algorithm, including state-action pair, reward function and update rule of Q value table. Then, a setup method of CB stops is designed and the path impedance function is constructed to obtain the optimal operating path between each of the two stops. Finally, we take three CB lines in Beijing as examples for numerical experiment, the theoretical and numerical results show that (i) compared with the current situation, although the actual operating cost of optimized route increases slightly, it is covered by the reduction of travel cost of passengers and the transmission risk of COVID-19 has also dropped significantly; (ii) the improved Q-learning algorithm can solve the problem of data transmission lag effectively and reduce the social total travel cost obviously.

Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial.

PURPOSE: To determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield. METHODS: Open-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18-44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER-) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes. RESULTS: Forty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =-2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups. CONCLUSIONS: Tamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group. TRIAL REGISTRATION: NCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled).

Full wafer scale electroluminescence properties of AlGaN-based deep ultraviolet LEDs with different well widths.

Deep ultraviolet (DUV) LEDs have great potential in sterilization, water, air purification, and other fields. In this work, DUV LED wafers with different quantum well (QW) widths were grown by metal-organic chemical vapor deposition. It is found that the light output power (LOP) and peak wavelength of all chips are not only related to the QW thickness but also affected by warpage. For the first time, to the best of our knowledge, a positive correlation between the LOP and peak wavelength of DUV LED chips on the same wafer was observed, which is very important for improving the yield of DUV LEDs and reducing costs. Furthermore, the influence of QW thickness on the external quantum efficiency (EQE) of DUV LED has also been investigated. As the thickness of the QW increases, the exciton localization effect decreases and the quantum confinement Stark effect increases. Consequently, DUV LED wafers with a QW thickness of 2 nm have the highest EQE and yield. These findings not only help to improve the efficiency of DUV LEDs but also provide new insights for evaluating the performance of DUV LED wafers.

Fertility Preservation and Infertility Treatment in Medical Training: An Assessment of Residency and Fellowship Program Directors' Attitudes.

Background: Given the concurrence of medical residency and fellowship training with typical childbearing years, trainees often must make difficult decisions regarding family planning, requiring the support of their residency and fellowship program directors (PDs) to guide them. Objective: Our hypothesis was that PDs have knowledge gaps and varying levels of support in terms of their trainees' fertility, and the goal of our study was to assess the knowledge and support of residency and fellowship PDs in the United States toward trainees' reproductive needs. Methods: Cross-sectional survey distributed to all residency and fellowship PDs providing contact information through the Accreditation Council for Graduate Medical Education website in August 2019. Results: Of 299 respondents, the most common lengths of leave reported were 6-8 weeks of maternity leave and under 2 weeks of paternity leave. A total of 57.2% did not know their program's insurance for infertility treatment, and 68.6% did not know fertility preservation coverage. A total of 52.2% of PDs were unaware of if their trainees faced infertility. PDs supported residents' needs through moral support (68.2%) and time off for appointments (65.2%). Similarly, most PDs (66.2%) never had a trainee express interest in fertility preservation to them but offered moral support (59.2%) and time off (48.5%). Respondents felt it was important to increase resources for trainees by increasing their awareness of needs (47.5%) and establishing reproduction-related policies (34.1%). Conclusion: The study found variations regarding PDs' knowledge and support levels for trainees' fertility needs. Most were unaware of their trainees' fertility needs, and many PDs felt it would be important to improve resources by increasing personal awareness and creating policies for support to promote reproductive health equity for trainees.

Effects of probiotic supplementation on natural killer cell function in healthy elderly individuals: a meta-analysis of randomized controlled trials.

To evaluate evidence for the role of probiotic supplementation in enhancing natural killer (NK) cell function in healthy elderly individuals. Five electronic databases were searched, and references of included articles and eligible reviews up to December 2019, with English language and human subject restrictions, were examined. Two independent reviewers identified randomized control trials (RCTs) of probiotic supplementation influencing NK cell function in healthy elderly individuals, assessed the quality of every article, and extracted data for subsequent meta-analysis. We identified six eligible trials including 364 healthy elderly subjects. Trials were heterogeneous in study design and probiotic supplementation (including genus, strain, dose, and duration). Five trials used Lactobacillus interventions alone or in combination with Bifidobacterium. Only one trial focused on Bacillus coagulans. The duration of supplementation ranged from 3 to 12 weeks, and the doses, from 1 × 109 to 4 × 1010 colony-forming units. Pooling data of eligible trials showed that probiotics significantly (P < 0.05) increased NK cell activity in healthy elderly individuals (standardized mean difference = 0.777, 95% confidence interval: 0.187‒1.366, P = 0.01, I2 = 84.6%). Although we obtained a significant outcome, the data do not provide convincing evidence for associations between probiotic supplementation and enhancement of NK cell function, given the small final number and very large heterogeneity. More RCTs with sufficient sample sizes and long-term follow-up are needed to focus on optimal probiotic dose, species, and duration of supplementation for healthy elderly individuals.

The association between gut butyrate-producing bacteria and non-small-cell lung cancer.

BACKGROUND: Recently, it has been found that the gut microbiota may affect the development of lung cancer through the "gut-lung axis." To investigate this relationship, we performed this study to determine whether the gut microbiota in non-small-cell lung cancer (NSCLC) patients is different from that in healthy adults. METHODS: Quantitative PCR (qPCR) was used to detect the expression levels of eight gut butyrate-producing bacteria in healthy adults and NSCLC patients. We enrolled 30 patients with NSCLC and 30 subjects from 100 healthy adults after matching for age and sex. RESULTS: Compared to healthy adults, most of the gut butyrate-producing bacteria in NSCLC patients were significantly decreased; these included Faecalibacterium prausnitzii, Clostridium leptum, Clostridial cluster I, Ruminococcus spp., Clostridial Cluster XIVa, and Roseburia spp. Among the gut butyrate-producing bacteria, we analyzed Clostridial cluster IV and Eubacterium rectale were not decreased in NSCLC patients. CONCLUSIONS: We conclude that NSCLC patients had gut butyrate-producing bacteria dysbiosis. Further studies should be performed to investigate the underlying mechanisms of how these specific bacteria affect lung cancer progression and prognosis.

Effects of nucleo(s)tide analogs therapy on chronic hepatitis B as evaluated by hepatosplenic radionuclide angiography.

OBJECTIVES: Hepatosplenic radionuclide angiography is a relatively noninvasive method for evaluating hepatic portal perfusion. We used hepatosplenic radionuclide angiography to assess the effects of nucleo(s)tide analogs therapy on patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent hepatosplenic radionuclide angiography from January 2012 to May 2017 at the First Affiliated Hospital, College of Medicine, Zhejiang University. The correlations between the results of routine laboratory tests and hepatic perfusion index (HPI) were evaluated. The Wilcoxon signed-rank test and one-way ANOVA of repeated measures were used to compare the HPIs of patients who received nucleo(s)tide analogs therapy. RESULTS: There is a positive correlation between HPI and cholinesterase and serum albumin (ALB) and a negative correlation between HPI and aspartate aminotransferase-to-platelet ratio index and bilirubin (TBiL). An improvement in HPI was observed in patients with an initial HPI <61% after nucleo(s)tide analogs therapy. CONCLUSIONS: Hepatosplenic radionuclide angiography can reflect the functional reserve of the liver and monitor liver fibrosis indirectly. It can also comprehensively assess the effects of antiviral therapy on patients with CHB, and antiviral therapy is critical for the treatment of hepatitis.

Anti-Müllerian hormone in association with euploid embryo transfer outcomes.

RESEARCH QUESTION: To investigate the association between anti-Müllerian hormone (AMH) concentration and maternal age with single euploid cryopreserved embryo transfer. DESIGN: Retrospective cohort study from 2014 to 2018 at an academic medical centre, including 389 cycles of IVF with 24-chromosome Day 5/6 preimplantation genetic testing for aneuploidies (PGT-A). Multivariate logistic regression was used to study AMH and age in relation to IVF outcomes (positive beta human chorionic gonadotrophin [bHCG], ongoing pregnancy and pregnancy loss rates) for patients with at least one euploid embryo for transfer, controlling for patient and cycle confounders. RESULTS: In this cohort the overall unadjusted positive bHCG rate was 69.2% and ongoing pregnancy rate was 52.7% per transfer, while the pregnancy loss rate was 23.4% per cycle with positive bHCG. Multivariate analysis found that compared with the reference group of AMH 1 to <5 ng/ml, AMH <1 and 5+ did not have any significant difference in positive bHCG (odds ratio, OR 0.65 [0.30-1.44] and 1.27 [0.61-2.65] for AMH <1 and AMH 5+, respectively) or ongoing pregnancy (OR 0.80 [0.43-1.50] and 1.41 [0.68-2.90]). However, AMH <1 had statistically significant lower euploid miscarriage rates compared with the reference group with OR 0.32 (0.12-0.85, P = 0.022); AMH 5+ did not have any statistical difference in miscarriage rate. Neither age at retrieval nor age at transfer were significantly associated with transfer outcomes. CONCLUSIONS: AMH concentration was not associated with positive bHCG or ongoing pregnancy for euploid embryo transfers after adjustment for potential confounders. Maternal age was not associated with euploid transfer outcomes. Further study is warranted in larger cohorts.

Miscarriage history association with euploid embryo transfer outcomes.

RESEARCH QUESTION: Is a history of miscarriage (including recurrent pregnancy loss) associated with euploid cryopreserved embryo transfer outcomes? DESIGN: Retrospective cohort study from 2014 to 2018 of patients at an academic medical centre, undergoing their first cycle of IVF with 24-chromosome Day 5/6 preimplantation genetic testing for aneuploidies (IVF-PGT-A). Multivariate logistic regression was used to investigate the relationship between history of miscarriage and euploid single cryopreserved embryo transfer outcomes (ongoing pregnancy, miscarriage), adjusting for an extensive list of patient and cycle confounders. RESULTS: In the study cohort of 283 patients, the overall unadjusted positive beta human chorionic gonadotrophin (bHCG) rate was 70.0%, ongoing pregnancy rate was 52.3%, and the total pregnancy loss (biochemical and clinical pregnancy loss) rate per positive bHCG cycle was 24.7%. While 35.3% of patients had a history of at least one previous miscarriage, 14.5% of patients had a history of recurrent pregnancy loss (RPL). For patients with a history of miscarriage, it was found that the adjusted odds ratios (OR) and 95% confidence intervals (CI) for positive bHCG were 1.30 (0.51-3.27), for ongoing pregnancy were 0.88 (0.38-2.03) and for total pregnancy loss were 1.41 (0.49-4.05), when compared with patients without a history of miscarriage. For RPL patients, OR for positive bHCG, ongoing pregnancy and total pregnancy loss also did not significantly differ when compared with patients with no history of miscarriage. CONCLUSIONS: In this cohort, there was no significant association between miscarriage history and euploid cryopreserved embryo transfer outcomes (ongoing pregnancy, total pregnancy loss) after adjustment for potential confounders. Further study in larger data sets is warranted.

Hormone replacement versus natural frozen embryo transfer for euploid embryos.

PURPOSE: The goal of this study is to investigate hormone replacement (HR) versus natural frozen embryo transfer outcomes for euploid embryos. METHODS: This is a retrospective cohort study at an academic medical center of patients undergoing in vitro fertilization with 24-chromosome day 5/6 preimplantation genetic testing for aneuploidies (PGT-A), from 2014 to 2018 using euploid single embryo frozen transfer. Multivariable logistic regression was used to study the association between transfer outcomes (ongoing pregnancy and miscarriage) with type of frozen euploid embryo transfer (HR versus natural) while controlling for multiple patient and cycle confounders. RESULTS: From a total of 389 cycles, 45.0% utilized HR frozen embryo transfer and 55.0% were natural cycles. We found that when compared to HR frozen embryo transfer, natural cycle frozen embryo transfer had significantly higher ongoing pregnancy rates (aOR 2.05, 1.27-3.31, p = 0.003). There was no significant difference in miscarriage rates between the two groups (aOR for natural 0.69, 95% CI 0.37-1.32, p = 0.27). When limiting the analysis to only the first transfer at our institution, findings were similar of higher ongoing pregnancy rates and no difference in miscarriage rates. CONCLUSIONS: In our multivariate analysis, we found that natural cycle single euploid frozen embryo transfer was associated with significantly higher ongoing pregnancy rates than HR transfer, with no difference in miscarriage rates.

Euploidy in relation to blastocyst sex and morphology.

PURPOSE: The objective of our study is to assess the relationship of embryo ploidy status in relation to embryo sex, morphological characteristics, and transfer parameters. METHODS: This is a retrospective cohort study at an academic medical center of patients who underwent in vitro fertilization with preimplantation genetic screening (PGS) from 2010 to 2015. Embryos were screened with 24-chromosome preimplantation genetic screening with day 5/6 trophectoderm biopsy. We investigated embryo euploidy in relation to morphology (expansion, inner cell mass, trophectoderm), embryo sex, biopsy day, and blastocyst cohort size. We used multivariate logistic regression to calculate odds ratios of euploidy in relation to these parameters. RESULTS: A total of 1559 embryos from 316 cycles and 233 patients (mean maternal age = 37.8 ± 4.2 years) were included in the analysis. Six hundred and twenty-eight blastocysts (40.3%) were found to be euploid. Expansion (p < 0.001), inner cell mass (ICM) (p < 0.01), and trophectoderm grade (p < 0.001) were significantly associated with embryo ploidy in bivariate models controlling for maternal age, while embryo sex, biopsy day, and blastocyst cohort size were not associated with embryo ploidy. In a multivariate model, we found that maternal age (p < 0.001), higher grade of expansion (p < 0.01), and better quality trophectoderm (p < 0.001 for A compared to C grade) remained significantly associated with increased embryo euploidy, but ICM grade was no longer significant. Embryo sex was not associated with ploidy status, though male embryos were found to be associated with higher trophectoderm scores (p < 0.02). CONCLUSIONS: This is the largest study to date to investigate PGS-tested embryo sex and ploidy status. While maternal age and some morphological parameters (expansion, trophectoderm grade) are associated with euploidy in our cohort, other parameters such as embryo sex, biopsy day, and cohort size are not. Though embryo sex was not associated with euploidy, male embryos were found to be associated with higher trophectoderm grades. Additional investigation in larger studies is warranted.

Use of Calcium Channel Blockers and Breast Cancer Risk in the Women's Health Initiative.

Background: Use of calcium channel blockers (CCBs) has been associated with increased risk of breast cancer in some, but not all, studies. Differences in reported associations from prior studies may be due, in part, to inadequate control of confounding factors.Methods: Participants were 28,561 postmenopausal women from the Women's Health Initiative who reported use of either CCBs or other antihypertensive medications (AHMs) at baseline; 1,402 incident breast cancer cases were diagnosed during 12 years of follow-up. Adjusted Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the associations between CCB use relative to other AHM use and breast cancer risk.Results: Use of CCBs was not associated with breast cancer risk (HR, 1.06; 95% CI, 0.94-1.20) relative to use of other AHMs. Associations approximated the null value when CCBs were considered by duration of use, length of action, or drug class.Conclusions: We provide additional evidence that CCBs do not influence breast cancer risk in postmenopausal women.Impact: The results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Cancer Epidemiol Biomarkers Prev; 26(8); 1345-8. ©2017 AACR.