Lifestyle and fertility-specific quality of life affect reproductive outcomes in couples undergoing in vitro fertilization.

Objective: A Mediterranean dietary pattern, sleeping habits, physical activity, and lifestyle appear to affect reproductive health. There are few reports about whether fertility-specific quality of life (QOL) is linked to infertility treatment outcomes. The aim of this study is to investigate when lifestyle factors and fertility-specific QOL are comprehensively considered, which factors influence assisted reproductive technology (ART) outcomes. Methods: This prospective cohort includes 291 women undergoing a first ART treatment at multiple centers in Japan and was designed to evaluate the influence of diet, physical activity, sleeping pattern, computer use duration, and fertility-specific quality of life tool (FertiQoL) score on ART treatment outcomes using a questionnaire. The primary endpoint was the good-quality blastocyst rate per oocyte retrieval and the secondary endpoints were a positive pregnancy test and gestational sac (GS) detection. Results: The good-quality blastocyst rate per oocyte retrieval tended to be negatively associated with frequent fish consumption. After all embryo transfer (ET) cycles, a positive pregnancy test tended to be positively associated with longer sleep and longer computer use (OR = 1.6, 95% CI = 0.9-2.7 and OR = 1.7, CI = 1.0-2.8, respectively) and negatively associated with a smoking partner (OR = 0.6, CI = 0.3-1.0). GS detection was positively and significantly associated with frequent olive oil intake and longer computer use (OR = 1.7, CI = 1.0-3.0 and OR = 1.7, CI = 1.0-3.0, respectively). After ET cycles with a single blastocyst, a positive pregnancy test was positively and significantly associated with longer computer use (OR = 2.0, CI = 1.1-3.7), while GS detection was significantly more likely in women with longer computer use (OR = 2.1, CI = 1.1-3.8) and tended to be more likely in women with a higher FertiQoL Total scaled treatment score (OR = 1.8, CI = 1.0-3.3). p < 0.05 was considered statistically significant and 0.05 ≤ p <0.01 as tendency. Conclusions: Olive oil may be an important factor in dietary habits. Fertility-specific QOL and smoking cessation guidance for partners are important for infertile couples.

Effects of the prenatal and postnatal nurturing environment on the phenotype and gut microbiota of mice with polycystic ovary syndrome induced by prenatal androgen exposure: a cross-fostering study.

The gut microbiome is implicated in the pathogenesis of polycystic ovary syndrome (PCOS), and prenatal androgen exposure is involved in the development of PCOS in later life. Our previous study of a mouse model of PCOS induced by prenatal dihydrotestosterone (DHT) exposure showed that the reproductive phenotype of PCOS appears from puberty, followed by the appearance of the metabolic phenotype after young adulthood, while changes in the gut microbiota was already apparent before puberty. To determine whether the prenatal or postnatal nurturing environment primarily contributes to these changes that characterize prenatally androgenized (PNA) offspring, we used a cross-fostering model to evaluate the effects of changes in the postnatal early-life environment of PNA offspring on the development of PCOS-like phenotypes and alterations in the gut microbiota in later life. Female PNA offspring fostered by normal dams (exposed to an abnormal prenatal environment only, fostered PNA) exhibited less marked PCOS-like phenotypes than PNA offspring, especially with respect to the metabolic phenotype. The gut microbiota of the fostered PNA offspring was similar to that of controls before adolescence, but differences between the fostered PNA and control groups became apparent after young adulthood. In conclusion, both prenatal androgen exposure and the postnatal early-life environment created by the DHT injection of mothers contribute to the development of PCOS-like phenotypes and the alterations in the gut microbiota that characterize PNA offspring. Thus, both the pre- and postnatal environments represent targets for the prevention of PCOS and the associated alteration in the gut microbiota in later life.

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed 'senescence-associated secretory phenotype' (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated ß-galactosidase (SA-ß-gal); and the SASP-related factor interleukin (IL)-6; were significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.

The prevalence of vulvovaginal symptoms in Japanese women of reproductive and perimenopausal ages: A cross-sectional study across generations.

AIM: This cross-sectional study evaluated vaginal health and hygiene practices among reproductive and perimenopausal women in Japan using an online-based questionnaire. METHODS: The questionnaire included 11 well-structured questions concerning vulvovaginal symptoms and hygiene care practices. Participants' responses were anonymized and analyzed descriptively. The relationships of age, family income, occupation, and childbearing with women's concerns regarding vaginal or vulvar problems were analyzed by chi-square tests. RESULTS: About 80% of women in their 20s to 50s in Japan reported experiencing vulvovaginal symptoms. Women in their 40s had significantly fewer symptoms than women in their 20s (p = 0.04), and women in their 50s had significantly fewer symptoms than all other age groups (20s, 30s, and 40s) (p < 0.001). Among symptomatic women, 77.5% did not discuss their symptoms with anyone else and only 10% visited doctors. About 12.5% of women reported taking special care of their vagina or vulva regularly, whereas 38.2% expressed a desire to try some form of care but had not yet done so. Of the women who did not take special care of their vagina or vulva, 46.2% lacked knowledge about proper care, 42.2% did not want to spend money on care, 30.5% did not want to discuss care with others, and 21.3% were psychologically reluctant. CONCLUSION: Determination of the prevalence of vulvovaginal symptoms among Japanese women can enhance understanding of this prevalent condition and its impact on women's health. These findings may help formulate effective public health interventions and promote better hygienic practices, thus improving the well-being of women in Japan.

The Association between Endometriosis and Obstructive Müllerian Anomalies.

It is unclear whether clinical background differs between endometriosis in adolescent patients with obstructive Müllerian anomalies and those without anomalies. The aim of the study is to identify the difference in clinical characteristics of endometriosis in patients with or without obstructive Müllerian anomalies. The study involved 12 patients aged under 24 years old who underwent primary surgery for obstructive Müllerian anomalies and 31 patients aged under 24 years old who underwent surgery for ovarian endometrioma. A total of 6 out of 12 cases with obstructive Müllerian anomalies developed endometriosis (4 Herlyn-Werner-Wunderlich syndrome, 2 non-communicating functional uterine horn, 2 cervical aplasia). The age at surgery was significantly younger in endometriosis with obstructive Müllerian anomalies, compared with those without obstructive Müllerian anomalies (17.8 ± 4.4 vs. 23.1 ± 1.3, p = 0.0007). The rate of endometrioma was 50.0% and the rate of hydrosalpinx was significantly higher (66.7% vs. 0%, p = 0.0002) in the group of obstructive Müllerian anomalies. The recurrence rate of endometriosis was 20.0% in the group of anomalies and 25.9% in the group of those without anomalies. Adolescent patients with obstructive Müllerian anomalies more easily developed endometriosis and co-occurred with higher rate of hematosalipinx.

Ulipristal (UPA) effects on rat ovaries: Unraveling follicle dynamics, ovulation inhibition, and safety implications for prolonged use.

Ulipristal (UPA), a selective progesterone receptor modulator, has both agonistic and antagonistic effects on progesterone receptors. UPA suppresses ovulation by inhibiting the luteinizing hormone (LH) surge from the pituitary gland; however, the direct effect of UPA on ovarian tissue remains poorly studied. In the present study, we examined the effects of UPA on the ovaries of rats. Rats were treated for 28 days with UPA, and the effects of UPA on ovarian tissue were examined histologically and the expression of antioxidant genes and cell death markers were also investigated. UPA treatment increased the number of primordial follicles at each treatment group, primordial follicles increased at all dose levels, but the size/magnitude of the effect decreased with the increasing dose. The number of primary and antral follicles tended to increase with increasing UPA levels. Furthermore, the decrease in primary follicle number could be attributed to the exhaustion of follicles, but the examination of proliferation markers, oxidative stress markers, and cell death markers revealed no remarkable toxic effects on ovarian tissues. These results suggest that UPA treatment promotes follicle development at each stage but inhibits ovulation by suppressing the LH surge, resulting in an increase in atretic follicles or unruptured luteinized cysts. These results suggest that UPA may not have both toxic effects on the ovary and a direct local effect on ovarian follicles, but we should be careful about the effects of prolonged UPA treatment in patients with uterine fibroids on their future fecundity.

Cellular senescence in the pathogenesis of ovarian dysfunction.

The follicular microenvironment is crucial for normal ovarian function, and intra-ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens the adverse environment of various tissues and plays critical roles in chronological aging and various pathological conditions. Cellular senescence involves cell-cycle arrest, a senescence-associated secretory phenotype (SASP), macromolecular damage, and dysmetabolism. In this review, I summarize the latest knowledge regarding the role of cellular senescence in pathological conditions in the ovary, in the context of reproduction. Specifically, cellular senescence is known to impair follicular and oocyte health in cisplatin- and cyclophosphamide-induced primary ovarian insufficiency and to contribute to the pathogenesis of polycystic ovary syndrome (PCOS). In addition, cellular senescence is induced during the decline in ovarian reserve that is associated with chronological aging, endometriosis, psychological stress, and obesity, but it remains unclear whether it plays a causative role in these conditions. Finally, I discuss the potential for use of cellular senescence as a novel therapeutic target. The modification of SASP using a senomorphic and/or the elimination of senescent cells using a senolytic represent promising therapeutic strategies. Further elucidation of the role of cellular senescence in the effects of various insults on ovarian reserve, including chronological aging, as well as in pathogenesis of ovarian pathologies, including PCOS, may facilitate a new era of reproductive medicine.

Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

PURPOSE: To clarify the reproductive outcomes of fertility preservation (FP) treatment. METHODS: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. RESULTS: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. CONCLUSION: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Assisted reproductive technology in Japan: A summary report for 2021 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) registry gathers comprehensive data from registered assisted reproductive technology (ART) facilities in Japan. Herein, we report 2021 ART cycle characteristics and outcomes. Methods: Descriptive statistics were used to summarize and analyze 2021 data. Results: In 2021, 625 ART facilities participated in the registry; 27 facilities did not conduct ART cycles and 598 registered treatment cycles. In total, 498 140 cycles were registered, and there were 69 797 neonates (increases of 10.7% and 15.5%, respectively, from the previous year). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles decreased in 2021; the number of neonates born was 2268 for IVF-embryo transfer (ET) cycles and 2850 for ICSI cycles. Frozen-thawed ET (FET) cycles increased markedly from 2020 (11.2% increase). In 2021, 239 428 FET cycles were conducted, resulting in 87 174 pregnancies and 64 679 neonates. For fresh transfers, the total single ET, singleton pregnancy rate, and singleton live birth rates were 82.7%, 97.0%, and 97.3%; for FET, these rates were 84.9%, 96.9%, and 97.1%. Conclusions: The 2021 Japanese ART registry analysis showed marked increases in both total treatment cycles and live births from the previous year.

Age and menstrual cycle may be important in establishing pregnancy in female athletes after retirement from competition.

BACKGROUND: Although it has been shown that amenorrhea associated with low energy availability or relative energy deficiency in sport affects body physiology in female athletes, the association between menstrual dysfunction during active sports careers and reproductive function after retirement is not clear. OBJECTIVE: To investigate the association between menstrual dysfunction during their active sports career and post-retirement infertility in female athletes. METHODS: A voluntary web-based survey was aimed at former female athletes who had become pregnant and gave birth to their first child after retirement. Nine multiple-choice questions were included, on maternal age, competition levels and menstrual cycles during active sports careers, time from retirement to pregnancy, the time of resumption of spontaneous menstruation after retirement, conception method, and mode of delivery, etc. Regarding cases of primary and secondary amenorrhea among the abnormal menstrual cycle group, only those whose spontaneous menstruation had not recovered from retirement to the time of pregnancy were included in the study. The association between the presence of abnormal menstrual cycles from active sports careers to post-retirement pregnancy and the implementation of infertility treatment was evaluated. RESULTS: The study population included 613 female athletes who became pregnant and gave birth to their first child after retiring from competitive sports. Of the 613 former athletes, the infertility treatment rate was 11.9%. The rate of infertility treatment was significantly higher in athletes with abnormal than normal menstrual cycles (17.1% vs. 10.2%, p = 0.0225). Multivariable logistic regression analysis showed that maternal age (adjusted odds ratio [OR] 1.194; 95% confidence interval [CI] 1.129, 1.262) and abnormal menstrual cycles (OR and 1.903; adjusted OR 1.105, 3.278) were the relevant factors for infertility treatment. CONCLUSION: It was suggested that menstrual dysfunction that persist from active sports careers to post-retirement may be a factor in infertility when trying to conceive after retirement.

Medical issues for female athletes returning to competition after childbirth.

BACKGROUND: In recent years, the number of athletes who aim to return to competition after childbirth has increased. However, few international reports have investigated complications during pregnancy, and changes in physical function after childbirth in many athletes. OBJECTIVE: To conduct a retrospective investigation of medical problems during pregnancy, and postpartum, in female athletes who aim to return to competition after childbirth, and to identify the barriers and facilitators for their return. METHODS: A voluntary web-based survey was aimed at former female athletes who became pregnant with their first child and gave birth during their active sports career. The survey items included respondent background, their exercise activities during and after childbirth, perinatal complications, mode of delivery, symptoms and physical function after childbirth. The participants were divided into a vaginal delivery group and a cesarean section group. RESULTS: Three hundred and twenty-eight (29.1 ± 5.1 years old) former athletes were included in the analysis, and about half reported undertaking exercise during pregnancy. The most common perinatal complication was anemia (27.4%). The appearance of any symptoms after childbirth, including low back pain (44.2%) and urinary incontinence (39.9%), was reported by 80.5%. The rate of urinary incontinence may be higher in the vaginal delivery than in the cesarean section group (p = 0.05). The most common physical decline after childbirth was in muscular strength, followed by speed and endurance. CONCLUSION: Addressing pregnancy-associated anemia and managing low back pain is critical for athletes aiming to return to competition after childbirth. Additionally, interventions to reduce the risk for and treat urinary incontinence are important. In addition, in order to return to competition after childbirth, it is important to strengthen muscles, especially the lower limbs and trunk, as well as to create a training program that takes into account the sport/events.

Differences in screening and treating relative energy deficiency in sport between the United States of America and Japan.

BACKGROUND: The diagnosis and treatment of relative energy deficiency in sport (RED-S) are challenging owing to variations in symptoms and the absence of specific guidelines. This study aimed to investigate differences in the diagnosis and follow-up of RED-S, its consequences, and related factors among sports medicine physicians with different backgrounds in Japan and the USA and examine the differences between the two countries. METHODS: An anonymous survey regarding the diagnosis and treatment processes of RED-S was distributed to sports medicine physicians via email. Respondents included 58 sports medicine physicians from the USA and 241 from Japan. RESULTS: The findings showed that 77.6% of the US physicians screened athletes for RED-S, whereas 17.5% of their Japanese counterparts did so. Moreover, 98.3% and 36.7% of the US and Japanese physicians, respectively, answered that they screened athletes for eating disorders upon suspicion of low energy availability. Logistic regression analysis revealed that the number of US sports medicine physicians who screened athletes for the female athlete triad (Triad) and RED-S (odds ratio [OR] = 12.78, P<0.001) and adhered to specific criteria for athlete suspension and return-to-play (OR=33.67, P<0.01) was higher than that of their Japanese counterparts. CONCLUSIONS: The prevalence of RED-S-related screening and treatment differed between US and Japanese sports medicine physicians. Educating sports medicine physicians about the diagnosis and treatment of athletes with possible signs of RED-S is important in treating female athletes and further investigations are required to identify why the physicians screened/not screened the athletes.

Differences of Bone Mineral Density by Characteristics of Sports in Amenorrheic Athletes.

Hypothalamic amenorrhea leads to a hypoestrogenic state, causing decreased bone mineral density (BMD), while strong impact loading on bone has been shown to increase BMD. The purpose of this study is to compare BMD in female athletes based on menstrual status and their sports/events by impact loading characteristics. BMD at the lumbar spine was measured by dual-energy X-ray absorptiometry and hormone level. The subjects were classified into four groups and BMD and hormone levels were compared among the four groups, which were divided into amenorrheic athletes (AAs) and eumenorrheic athletes (EAs). This study recruited 410 female athletes (164 in the AAs and 246 in the EAs), 55 athletes in non-impact sports, 123 in low-impact sports, 141 in multidirectional sports, and 91 in high-impact sports. In the AAs group, BMD Z-score was lowest in low-impact sports (Z-score: -1.53 [-1.76, -1.30]), and was highest in high-impact sports (Z-score: 0.02 [-0.34, 0.38]). In multidirectional and high-impact sports, BMD Z-score in the AAs group did not show results lower than the average for non-athletes. When screening female athletes for low BMD, it is important to evaluate the risk of low BMD based on the impact loading characteristics of their sports/events, in addition to the menstrual state.

The Role of Cellular Senescence in Cyclophosphamide-Induced Primary Ovarian Insufficiency.

Young female cancer patients can develop chemotherapy-induced primary ovarian insufficiency (POI). Cyclophosphamide (Cy) is one of the most widely used chemotherapies and has the highest risk of damaging the ovaries. Recent studies elucidated the pivotal roles of cellular senescence, which is characterized by permanent cell growth arrest, in the pathologies of various diseases. Moreover, several promising senolytics, including dasatinib and quercetin (DQ), which remove senescent cells, are being developed. In the present study, we investigated whether cellular senescence is involved in Cy-induced POI and whether DQ treatment rescues Cy-induced ovarian damage. Expression of the cellular senescence markers p16, p21, p53, and γH2AX was upregulated in granulosa cells of POI mice and in human granulosa cells treated with Cy, which was abrogated by DQ treatment. The administration of Cy decreased the numbers of primordial and primary follicles, with a concomitant increase in the ratio of growing to dormant follicles, which was partially rescued by DQ. Moreover, DQ treatment significantly improved the response to ovulation induction and fertility in POI mice by extending reproductive life. Thus, cellular senescence plays critical roles in Cy-induced POI, and targeting senescent cells with senolytics, such as DQ, might be a promising strategy to protect against Cy-induced ovarian damage.

Pregnancy is associated with reduced progression of symptomatic adenomyosis: a retrospective pilot study.

BACKGROUND: Adenomyosis is a common gynecological disease in women of reproductive age and causes various symptoms such as dysmenorrhea and heavy menstrual bleeding. However, the influence of pregnancy on the progression of adenomyosis remains unclear. The insight into whether the size of adenomyosis is increased, decreased, or unchanged during pregnancy is also undetermined. The current study aimed to evaluate the influence of pregnancy in patients with symptomatic adenomyosis. METHODS: This study retrospectively enrolled patients diagnosed with adenomyosis by magnetic resonance imaging between 2015 and 2022 at The University of Tokyo Hospital. Uterine size changes were evaluated by two imaging examinations. In the pregnancy group, the patients did not receive any hormonal and surgical treatments, except cesarean section, but experienced pregnancy and delivery between the first and second imaging examinations. In the control group (nonpregnancy group), the patients experienced neither hormonal and surgical treatments nor pregnancy from at least 1 year before the first imaging to the second imaging. The enlargement rate of the uterine size per year (percentage) was calculated by the uterine volume changes (cm3) divided by the interval (years) between two imaging examinations. The enlargement rate of the uterine size per year was compared between the pregnancy group and the control group. RESULTS: Thirteen and 11 patients with symptomatic adenomyosis were included in the pregnancy group and in the control group, respectively. The pregnancy group had a lower enlargement rate per year than the control group (mean ± SE: -7.4% ± 3.6% vs. 48.0% ± 18.5%, P < 0.001), indicating that the size of the uterus with adenomyosis did not change in the pregnancy group. CONCLUSIONS: Pregnancy is associated with reduced progression of symptomatic adenomyosis.

Challenges to Widespread Use of Fertility Preservation Facilities for Pediatric Cancer Patients in Japan.

Purpose: Although fertility preservation for pediatric cancer patients is becoming more widespread in Japan, some facilities do not provide sufficient information regarding fertility. This study aimed to elucidate the problems pertaining to the lack of information about fertility among patients. Methods: Based on a 2020 survey, seminars addressing fertility preservation were held from the Designated Pediatric Cancer Care Hospitals in each of the seven blocks in Japan to their partner hospital (pediatric cancer hospitals). The seminar consisted of lectures and group discussions, and a questionnaire was also administered after each seminar. Results: In the group discussions, a lack of explanations to patients and explanatory materials for children were cited as issues by many facilities. The survey results revealed a lack of material explaining fertility preservation and a lack of knowledge among health care providers. There were also many requests to use the patient explanation videos presented at the seminar. Conclusion: The results indicate that further education for health care providers by seminar and other sources and enhancement of explanatory materials are important for fertility preservation in pediatric cancer hospitals in Japan.

Fact-finding survey on assisted reproductive technology in Japan.

AIMS: In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. METHODS: ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. RESULTS: Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60-300] cycles), followed by mild ovarian simulation (60 [30-200]). Additionally, freeze-thaw embryo transfer cycles (300 [120-750]) were performed more frequently than fresh embryo transfer cycles (30 [30-60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. CONCLUSIONS: The implementation of frozen-thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

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.

Development of University of Tokyo's eating disorders inventory in female athletes.

AIMS: This study aimed to develop a scale to screen for eating disorders in female athletes. METHODS: Preliminary survey: A total of 275 female athletes (mean age: 19.4 ± 1.0 years) and 7 female athletes diagnosed with eating disorders (mean age: 20.1 ± 2.5 years) were administered screening items prepared based on an existing scale, followed by exploratory factor analysis. Main survey: Six items, relating to three factors, were extracted, and 201 female athletes (mean age: 22.3 ± 4.8 years) and 6 female athletes diagnosed with current or a history of eating disorders (mean age: 18.8 ± 2.9 years) were queried. The diagnostic validity of the scale was then evaluated. RESULTS: Preliminary survey: Questions (α = 0.71) were extracted from six items, relating to three factors, and collectively termed the University of Tokyo's eating disorders inventory in female athletes (TEDIFA). To determine the scale cut-off score, ROC analysis was performed with the total score, and the cut-off and gray zone scores were set at 13 and 11, respectively. Main survey: At the cut-off score of 13, AUC, sensitivity, and specificity were 0.83 (p < 0.05), 75%, and 90%, respectively. CONCLUSIONS: The scale that was developed, TEDIFA, consisted of six items. The cut-off scores were set at 11 for the gray zone (sensitivity: 75%; specificity: 56%; accurate diagnosis rate: 60%), and 13 for positivity (sensitivity: 75%; specificity: 90%; accurate diagnosis rate: 87%), demonstrating the reliability and validity of the scale.

Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.