Impact of daily breakfast intake on the outcomes of assisted reproductive technology procedures.

OBJECTIVE: To assess the relationship between meal consumption frequency and assisted reproductive technology (ART) outcomes among female patients with infertility. RESEARCH METHODS & PROCEDURES: This cohort study was conducted from February 2022 to January 2024 at Tokyo Medical University Hospital. Overall, 101 female patients with infertility issues and without a history of stroke, heart disease, cancer, or type 1 or type 2 diabetes were enrolled in this study. The factors extracted from the questionnaire included demographic information, meal consumption frequency before ART and at 20 years of age, smoking status, and alcohol consumption status. Data on other factors, including age, body mass index, anti-Müllerian hormone level, and parity history, were collected from medical records. The assessed clinical outcomes included number of transplanted embryos, clinical pregnancies, ongoing pregnancies, live births, and miscarriages. RESULTS: After adjusting for potential confounding factors, including age, smoking status, alcohol consumption status, body mass index, anti-Müllerian hormone level, and parity history, a multivariate analysis of ART outcomes was performed. Patients were categorized into groups based on the frequency of weekly consumption of breakfast, lunch, and dinner. Patients who consumed breakfast 6-7 times a week were significantly more likely to have higher rates of live birth and lower rates of miscarriage in pregnancies conceived through ART. CONCLUSIONS: Consumption of breakfast 6-7 times a week before ART was associated with increased success rates following ART. This highlights the potential importance of regular breakfast consumption for optimizing ART outcomes.

Out-of-pocket fertility preservation expenses: data from a Japanese nationwide multicenter survey.

BACKGROUND: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs. METHODS: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%). RESULTS: Our findings show that approximately one-third of the costs was borne by the patients. CONCLUSION: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.

Case report: Rare heterozygous variant in the NR5A1 gene causing 46,XY complete gonadal dysgenesis with a non-communicating rudimentary uterus.

The nuclear receptor subfamily 5 group A member 1 (NR5A1) gene encodes NR5A1, also known as steroidogenic factor 1, a crucial transcriptional factor regulating adrenal and gonadal development and function. Although pathogenic variants in NR5A1 are known to cause a spectrum of disorders of sex development (DSD), individuals with 46,XY DSD with fully female internal and external genitalia are relatively rare. Herein, we present the case of a patient with 46,XY complete gonadal dysgenesis (CGD) who had a non-communicating rudimentary uterus due to a c.132_134del (p.Asn44del) heterozygous in-frame-deletion in NR5A1 that was diagnosed while treating a pelvic mass in which gynecological malignancy could not be disregarded. Unlike two previous cases with the p.Asn44del variant, this case presented with CGD, a severe DSD phenotype, and we found that the oligogenic inheritance of DSD-causative genes such as SRY, DHX37, SLC26A8, and CFTR may have affected the severity of the clinical phenotype.

A case of Herlyn-Werner-Wunderlich syndrome with exacerbation of hematometra after adnexectomy.

A 27-year-old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn-Werner-Wunderlich syndrome. Treatment must permit the outflow of menstrual blood.

MR Relaxometry for Discriminating Malignant Ovarian Cystic Tumors: A Prospective Multicenter Cohort Study.

BACKGROUND: Endometriosis-associated ovarian cancer (EAOC) is a well-known type of cancer that arises from ovarian endometrioma (OE). OE contains iron-rich fluid in its cysts due to repeated hemorrhages in the ovaries. However, distinguishing between benign and malignant tumors can be challenging. We conducted a retrospective study on magnetic resonance (MR) relaxometry of cyst fluid to distinguish EAOC from OE and reported that this method showed good accuracy. The purpose of this study is to evaluate the accuracy of a non-invasive method in re-evaluating pre-surgical diagnosis of malignancy by a prospective multicenter cohort study. METHODS: After the standard diagnosis process, the R2 values were obtained using a 3T system. Data on the patients were then collected through the Case Report Form (CRF). Between December 2018 and March 2023, six hospitals enrolled 109 patients. Out of these, 81 patients met the criteria required for the study. RESULTS: The R2 values calculated using MR relaxometry showed good discriminating ability with a cut-off of 15.74 (sensitivity 80.6%, specificity 75.0%, AUC = 0.750, p < 0.001) when considering atypical or borderline tumors as EAOC. When atypical and borderline cases were grouped as OE, EAOC could be distinguished with a cut-off of 16.87 (sensitivity 87.0%, specificity 61.1%). CONCLUSIONS: MR relaxometry has proven to be an effective tool for discriminating EAOC from OE. Regular use of this method is expected to provide significant insights for clinical practice.

Boosting biodiversity monitoring using smartphone-driven, rapidly accumulating community-sourced data.

Comprehensive biodiversity data is crucial for ecosystem protection. The Biome mobile app, launched in Japan, efficiently gathers species observations from the public using species identification algorithms and gamification elements. The app has amassed >6 million observations since 2019. Nonetheless, community-sourced data may exhibit spatial and taxonomic biases. Species distribution models (SDMs) estimate species distribution while accommodating such bias. Here, we investigated the quality of Biome data and its impact on SDM performance. Species identification accuracy exceeds 95% for birds, reptiles, mammals, and amphibians, but seed plants, molluscs, and fishes scored below 90%. Our SDMs for 132 terrestrial plants and animals across Japan revealed that incorporating Biome data into traditional survey data improved accuracy. For endangered species, traditional survey data required >2000 records for accurate models (Boyce index ≥ 0.9), while blending the two data sources reduced this to around 300. The uniform coverage of urban-natural gradients by Biome data, compared to traditional data biased towards natural areas, may explain this improvement. Combining multiple data sources better estimates species distributions, aiding in protected area designation and ecosystem service assessment. Establishing a platform for accumulating community-sourced distribution data will contribute to conserving and monitoring natural ecosystems.

The internet has allowed people to share their experiences through images, videos or audio recordings. This has led to the creation of online communities around a variety of topics, including biodiversity. In 2019, a smartphone app, called Biome, was created to fuel biodiversity engagement by making wildlife surveying an easy and fun activity via gamification and assisted species identification through image recognition and ecological analyses. These types of observations are essential for understanding biological communities and species habitats, and they can indicate where and when species occur. Across Japan, Biome has gathered over 6.5 million observations of different species. For biologists, this type of data is extremely useful because it is continuous and enables advanced statistical estimations of species distributions. The fact that the approach is enjoyable to the user also means more people are willing to participate, lowering the barriers to collecting data about biodiversity loss. However, questions remain regarding whether community-sourced data is robust enough for scientific purposes. To address this, Atsumi et al. investigated the quality of occurrence data collected in Biome. The researchers found that community identification of birds, reptiles, mammals and amphibians all exceeded 95% in accuracy. However, the accuracy fell for harder-to-judge seed plants, molluscs and fish species, ranging below 90%. Atsumi et al. also compared how estimated distributions of each species changed when only scientific data was used, versus when it was combined with community data. To perform this analysis, the scientists recognized variations in observation efforts across different locations and individuals and adjusted for these biases in their estimations. They found that adding community-sourced data significantly improved the accuracy of species distribution estimations, including endangered species. Atsumi et al. demonstrate that Biome data is useful when deciding which areas to designate as protected in terms of biodiversity. Additionally, these data can provide guidance for stakeholder-informed ecosystem service assessments. The element of rapid and reliable data collection can contribute to growing positive attitudes towards nature and biodiversity, The platform's community-driven nature also indicates an increase in biodiversity awareness and may link to crafting informative socio-environmental policy commitments.

Toward the Establishment of a Harmonized Physicochemical Profiling Platform for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order Structure Influences Physical Properties.

Oligonucleotides are short nucleic acids that serve as one of the most promising classes of drug modality. However, attempts to establish a physicochemical evaluation platform of oligonucleotides for acquiring a comprehensive view of their properties have been limited. As the chemical stability and the efficacy as well as the solution properties at a high concentration should be related to their higher-order structure and intra-/intermolecular interactions, their detailed understanding enables effective formulation development. Here, the higher-order structure and the thermodynamic stability of the thrombin-binding aptamer (TBA) and four modified TBAs, which have similar sequences but were expected to have different higher-order structures, were evaluated using ultraviolet spectroscopy (UV), circular dichroism (CD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). Then, the relationship between the higher-order structure and the solution properties including solubility, viscosity, and stability was investigated. The impact of the higher-order structure on the antithrombin activity was also confirmed. The higher-order structure and intra-/intermolecular interactions of the oligonucleotides were affected by types of buffers because of different potassium concentrations, which are crucial for the formation of the G-quadruplex structure. Consequently, solution properties, such as solubility and viscosity, chemical stability, and antithrombin activity, were also influenced. Each instrumental analysis had a complemental role in investigating the higher-order structure of TBA and modified TBAs. The utility of each physicochemical characterization method during the preclinical developmental stages is also discussed.

Robot-assisted Surgery with Para-aortic Lymphadenectomy for Endometrial Cancer: A Preliminary Report.

Objectives: There are few reported cases of robot-assisted surgery for endometrial cancer with para-aortic lymphadenectomy (PAL) in Japan. Therefore, this study aimed to examine the clinical outcomes of robot-assisted surgery with PAL for endometrial cancer. Materials and Methods: This retrospective cohort study was analyzed 13 endometrial cancer patients who underwent robotic surgery with PAL between January 2011 and October 2018 at our hospital. We examined their perioperative complications and oncological outcomes. Results: The median follow-up period, median overall survival, and disease-free interval were 80 months, 79 months (61-120), and 79 months (5-120), respectively. There were two (15.3%) cases of perioperative complications of Clavien-Dindo Class II or higher and three (23.0%) cases of recurrence. Conclusion: Our results showed that the surgical and oncological outcomes of robot-assisted surgery for endometrial cancer with PAL were comparable with those of other developed countries.

Miscarriage-Related Acute Kidney Injury: A Case Report.

Background: Pregnancy-related acute kidney injury (Pr-AKI) is associated with significant maternal and fetal morbidity and mortality, with a three- to four-fold increase in perinatal mortality. Pr-AKI can arise from various obstetric complications, such as hyperemesis gravidarum, septic abortion, hypertensive disorders of pregnancy, pyelonephritis, and antiphospholipid antibody syndrome. Therefore, early diagnosis and appropriate intervention, including the identification of the underlying etiology, are important to effectively manage Pr-AKI. Therefore, we report a case of Pr-AKI after early miscarriage in a patient without hyperemesis gravidarum or septic abortion whose renal function gradually improved postoperatively for miscarriage. Case Presentation: A 34-year-old primigravid woman was referred to us for perinatal management at 6 weeks of gestation. Unfortunately, she was diagnosed with miscarriage 1 week later. The patient had no history of hyperemesis gravidarum or septic abortion; however, she developed oliguria, and her serum creatinine and blood urea nitrogen levels were abnormally increased. Consequently, she underwent a renal biopsy to evaluate renal dysfunction, which indicated tubulointerstitial damage. The patient also underwent manual vacuum aspiration for a miscarriage. Postoperatively, her urine output increased, and her renal function improved. She was determined to have experienced Pr-AKI due to her miscarriage. Conclusion: Our patient had Pr-AKI after a miscarriage in the absence of other causes. This case report highlights the presence of unknown causes of Pr-AKI, warranting further research for the development of preventive interventions.

Pregnancy and delivery in an advanced cancer survivor with immune checkpoint inhibitor-induced type 1 diabetes: a case report.

PURPOSE: Given the rarity and elderly onset of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (ICI-T1DM), cases leading to delivery are rare. METHOD: To our knowledge, this is the first case report of childbirth in a patient with ICI-T1DM after cancer survival. A 32-year-old woman was started on Nivolumab for metastatic parotid cancers one year after total parotidectomy. RESULT: The patient developed ICI-T1DM after 43 cycles and started multiple daily insulin therapy and self-monitoring of blood glucose. Complete response was maintained for 2 years by nivolumab, and she finished nivolumab in 77 cycles to attempt pregnancy. During the follow-up period, she began using a sensor-augmented pump (SAP). She had undetectable serum and urinary C-peptide when she started SAP. Her HbA1c level decreased from 7.8 to 6.6% without increasing hypoglycemia in one year. The patient remained in complete response after ICI discontinuation, and embryo transfer was initiated. Pregnancy was confirmed after a second embryo transfer (21 months after ICI discontinuation). At 36 weeks and 6 days, an emergency cesarean section was performed due to the onset of preeclampsia. The baby had hypospadias and bifid scrotum but no other complications or neonatal intensive care unit admission. CONCLUSION: Because ICI discontinuation and ICI-T1DM carry risks for the patient and child, the decision regarding pregnancy warrants careful consideration. Diabetologists should collaborate with patients and other clinical departments to develop a treatment plan for childbirth.

BMAL1 positively correlates with genes regulating steroidogenesis in human luteinized granulosa cells.

In brief: In this study, we examined the relationship between BMAL1 expression and the genes regulating steroid biosynthesis in human luteinized granulosa cells. BMAL1 function is crucial for steroid production and proper ovarian function, highlighting the importance of circadian clock regulation in female reproductive health. Abstract: Human luteinized granulosa cells were collected to analyze circadian clock gene expression and its effect on the genes regulating steroid biosynthesis. We used siRNA to knock down the expression of BMAL1 in KGN cells. We measured the expression levels of genes regulating steroid biosynthesis and circadian clock RT-qPCR. We demonstrated that BMAL1 expression positively correlates with genes regulating steroid biosynthesis (CYP11A1, CYP19A1, STAR, and ESR2). The knockdown of BMAL1 in KGN cells revealed a significant decrease in steroid synthase expression. In contrast, when BMAL1 was overexpressed in KGN and HGL5 cells, we observed a significant increase in the expression of steroid synthases, such as CYP11A1 and CYP19A1. These results indicated that BMAL1 positively controls 17ß-estradiol (E2) secretion in granulosa cells. We also demonstrated that dexamethasone synchronization in KGN cells enhanced the rhythmic alterations in circadian clock genes. Our study suggests that BMAL1 plays a critical role in steroid biosynthesis in human luteinized granulosa cells, thereby emphasizing the importance of BMAL1 in the regulation of reproductive physiology.

miR­146a­5p and miR­191­5p as novel diagnostic marker candidates for ovarian clear cell carcinoma.

Ovarian cancer is a malignant gynecologic disease rarely diagnosed in the early stages. Among the various types of ovarian cancer, clear cell carcinoma has a poor prognosis due to its malignant potential. MicroRNAs (miRNAs/miRs) regulate gene expression in cells by suppressing the translation of target genes or by degrading the target mRNA. miRNAs are also secreted from the cells in the blood, binding to proteins or lipids and assisting in cell-cell communication. Therefore, serum miRNAs may be considered potential diagnostic biomarkers for ovarian cancer. The present study investigated and identified specific miRNAs associated with ovarian clear cell carcinoma and compared them to those in ovarian endometrioma samples and healthy controls. CA125, an ovarian tumor marker, did not differ between patients with ovarian clear cell carcinoma, endometriosis or healthy controls. Subsequently, four miRNAs (miR-146a-5p, miR-191-5p, miR-484 and miR-574-3p) were analyzed. The expression levels of miR-146a-5p and miR-191-5p were significantly increased in the serum samples from patients with ovarian clear cell carcinoma compared with those in the healthy controls, but there was no significant difference compared with in patients with endometriosis. Furthermore, the bioinformatics analysis showed that CCND2 and NOTCH2 were the candidate target genes of miR-146a-5p and miR-191-5p. In conclusion, the results of the present study demonstrated that miR-146a-5p and miR-191-5p may be useful as early and non-invasive diagnostic tools in ovarian clear cell carcinoma. These miRNAs can help in distinguishing between ovarian clear cell carcinoma and ovarian endometrioma. To the best of our knowledge, no previous studies have screened any candidates specifically for ovarian clear cell carcinoma.

The Long-Term Outcome of Children Conceived Through Assisted Reproductive Technology.

Assisted reproductive technology (ART) led to the birth of 60,381 infants in 2020 in Japan. This number is set to increase as the future interest in ART is anticipated to rise. Couples receiving ART are monitoring the outcomes of these treatments to see whether any differences exist between babies conceived naturally and those conceived via ART. This study investigated the relationship between the long-term outcome of children born from ART with a focus on physical and psychomotor developments. A large volume of data concerning each relationship with ART was collected from various observational studies. Several findings indicate that, over time, the physical characteristics of babies born by ART, and those born naturally are comparable. However, some reports indicate that, until they reach school age, there may be a small difference in growth. ART and naturally conceived children do not vary in academic achievement or attention deficit hyperactivity disorder. Taken together, it is difficult to conclude with certainty that ART is the source of these differences since they may arise from the child's genetic factors or their environment.

Retrospective comparative study of robot-assisted surgery, laparoscopic surgery, and laparotomy for endometrial cancer in patients with a low risk of recurrence.

AIM: Minimally invasive surgeries for endometrial cancer are increasing worldwide. In Japan, some articles have examined surgical outcomes, but only a few have addressed oncological outcomes. This study aims to compare robot surgery, laparoscopic surgery, and laparotomy in terms of surgical and oncological outcomes within a low-risk group for endometrial cancer recurrence. METHODS: This study included patients with endometrial cancer deemed to be at low risk of recurrence and who underwent surgery between January 2011 and December 2020. We studied 99 patients who underwent robot surgery, 85 patients who underwent laparotomy, and 77 patients who underwent laparoscopic surgery. Surgical and oncological outcomes were compared retrospectively for these groups of patients. RESULTS: The median follow-up period was 47, 61, and 60 months in the laparotomy, laparoscopy, and robotic groups, respectively. The three groups had similar perioperative and pathological data. No significant differences in overall survival and disease-free survival were observed among the groups. Univariate and multivariate analyses conducted on the overall study population for disease-free survival and overall survival showed that the surgical approach did not have any influence. Minimally invasive surgery groups had longer operating times compared to the laparotomy group, but they had significantly less blood loss. The number of resected pelvic lymph nodes was similar, and the complication rate was not significant. CONCLUSIONS: Robot-assisted surgery and laparoscopic surgery were found to be less invasive and showed similar oncologic outcomes compared to laparotomy surgery for endometrial cancer in patients with a low risk of recurrence.

Ovarian Mesonephric-like Adenocarcinoma Recurring With a Rhabdomyosarcoma Component: A Case Report.

Mesonephric-like adenocarcinoma (MLA) has recently been described as a tumor of the endometrium or ovaries, which, morphologically and immunohistochemically, resembles mesonephric adenocarcinoma arising mostly in the uterine cervix. Herein, we report, to our knowledge, the first case of ovarian MLA that developed into an extremely rapidly growing recurrent mesonephric-like carcinosarcoma, as confirmed by a genomic profiling test. A 51-year-old woman underwent chemotherapy with complete debulking surgery for ovarian carcinoma. Pathologically, the patient was diagnosed with stage IVB ovarian MLA. Subsequent to 15 months of complete remission, an enhanced computed tomography scan revealed a solid tumor of 10 cm diameter in the abdominal cavity. Secondary surgery was terminated with a 2 cm 2 tumor biopsy specimen collection considering perioperative complications. Histologically, the tumor consisted of short spindle cells, and immunohistochemical staining revealed a rhabdomyosarcomatous profile without an epithelial component. Despite treatment for the sarcoma, she died 3 months after the detection of the tumor. The genomic profiling of the primary ovarian carcinoma and secondary resected tumor biopsy specimens revealed an identical KRAS mutation in both. Therefore, we concluded that the ovarian MLA recurred with a rhabdomyosarcoma component.

Regulatory action of PGRMC1 on cyclic AMP-mediated COX2 expression in human endometrial cells.

Human endometrial stromal cells (ESCs) undergo differentiation, known as decidualization, and endometrial epithelial cells mature around the embryo implantation stage. In the uterus, cyclooxygenase 2 (COX2), the rate-limiting enzyme that produces prostaglandin E2, is expressed in endometrial stromal and epithelial cells, and promotes decidualization of the former cells. Our recent study demonstrated that progesterone receptor membrane component 1 (PGRMC1) is downregulated during decidualization and may be involved in cellular senescence associated with decidualization via the transcription factor forkhead box protein O1 (FOXO1). Therefore, we investigated the role of PGRMC1 in COX2 expression during differentiation and maturation of endometrial stromal and epithelial cells. Inhibition or knockdown of PGRMC1 significantly enhanced differentiation stimuli-induced COX2 expression in both cell types. However, this COX2 expression was suppressed by FOXO1 knockdown or nuclear factor-kappa B (NF-κB) inhibition. Silencing of COX2 expression inhibited PGRMC1 knockdown-induced expression of decidual markers in ESCs. Thus, PGRMC1 may be linked to FOXO1- and NF-κB-mediated COX2 expression in endometrial cells. Taken together, our data suggest that downregulation of PGRMC1 expression facilitates differentiation of endometrial cells, i.e., decidualization and glandular maturation, via upregulation of COX2 expression.

Sirtuin 1 is a potential therapeutic candidate gene for fetal growth restriction via insulin-like 4.

OBJECTIVE: Insufficient placental development causes various obstetric complications, including fetal growth restriction (FGR). The Sirtuin 1 (SIRT1) and insulin-like 4 (INSL4) protein-coding genes have been demonstrated to play an important role in placental development. However, no treatment for FGR is available due to placental dysfunction. Therefore, this study aimed to examine the potential of the SIRT1-INSL4 axis as a treatment candidate for FGR caused by insufficient placental development. METHODS: Twenty patients were enrolled, including 10 with FGR and 10 full-term controls. FGR and control placental samples were collected. Quantitative real-time polymerase chain reaction, immunohistochemical analysis, and western blotting were used to analyze INSL4 and SIRT1 expression. An in-vitro loss-of-function approach with the human choriocarcinoma cell line BeWo was applied for functional analyses of SIRT1 in placental development. BeWo cells were differentiated into syncytiotrophoblasts by silencing SIRT1 using small interfering RNA. SIRT1 activator was added during differentiation of SIRT1-knockdown BeWo cells into syncytiotrophoblasts. RESULTS: The FGR samples had lower INSL4 and SIRT1 mRNA and protein expression levels than the control samples. Immunohistochemistry showed that both SIRT1 and INSL4 were expressed mainly in syncytiotrophoblasts. In-vitro analyses showed that SIRT1 knockdown decreased INSL4 expression; however, SIRT1 activator restored SIRT1 expression in SIRT1-silenced BeWo cells. CONCLUSIONS: SIRT1 and INSL4 are downregulated in the placenta of FGR, and INSL4 is regulated by SIRT1. These findings indicate that the SIRT1-INSL4 axis may be a potential therapeutic target for FGR.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma.

Uterine leiomyomas are smooth-muscle tumors originating in the myometrium and are the most common pelvic tumors in women of reproductive age. Symptomatic tumors may result in abnormal uterine bleeding, bladder dysfunction, pelvic discomfort, and reproductive issues, such as infertility and miscarriage. There are currently few non-invasive treatments for leiomyoma, but there are no practical early intervention or preventive methods. In this study, human uterine leiomyoma and myometrial tissues were used to detect the protein and mRNA expression levels of UCHL1. To explore the effects of UCHL1 knockdown and inhibition in leiomyoma and myometrial cells, we determined the mRNA expressions of COL1A1 and COL3A1. Collagen gel contraction and wound-healing assays were performed on myometrial and leiomyoma cells. We found that UCHL1 expression was considerably higher in uterine leiomyomas than in the myometrium. COL1A1 and COL3A1 expression levels were downregulated after inhibition of UCHL1 in human leiomyoma cells. Furthermore, the elimination of UCHL1 significantly decreased the migration and contractility of leiomyoma cells. In conclusion, these results indicate that UCHL1 is involved in the growth of leiomyoma in humans. For the treatment of uterine leiomyoma, targeting UCHL1 activity may be a unique and possible therapeutic strategy.