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AIM: To clarify the diagnostic process of the causative disease of abnormal uterine bleeding (AUB) in Japan according to the International Federation of Gynecology and Obstetrics AUB diagnostic system. METHODS: Patients diagnosed with AUB were included in a nationwide survey of AUB conducted during any 2-week period between December 2019 and January 2020. The second survey included information on patient background, AUB symptoms, examinations for diagnosing AUB, the order in which they were performed, and the causative diseases of AUB. RESULTS: Correspondence analysis showed an association between hormonal testing, hysterosalpingography, and magnetic resonance imaging (MRI) in patients with amenorrhea, and heavy menstrual bleeding was strongly correlated with various examinations, such as coagulation tests, pelvic MRI, and endometrial cytology or biopsy. The results also indicated that each AUB causative disease can be diagnosed based on a specific examination profile. CONCLUSION: We clarified the process of diagnosing the causative disease of AUB in our country and determined that it was mainly diagnosed by imaging and pathological examination in cases of structural disease. The high rate of AUB-E and the low rate of AUB-C are possibly associated with specific examination trends in Japan. The results of this study will be useful for the development of a standard protocol for AUB diagnosis in our country.
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Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)-protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated.
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AIM: To establish cut-off values for anti-Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence-Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria. METHODS: Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut-off values for AMH and AFC. RESULTS: Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut-off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20-29 and 30-39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut-off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH. CONCLUSION: The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria.
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Hormona Antimülleriana , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/sangre , Hormona Antimülleriana/sangre , Femenino , Adulto , Japón , Adulto Joven , Folículo Ovárico , Valores de Referencia , Pueblos del Este de AsiaRESUMEN
AIM: To identify factors influencing the Trendelenburg angle required during laparoscopic gynecological surgery. METHODS: Patients who underwent laparoscopic surgery at a single university hospital between May 1, 2019, and March 31, 2021 were enrolled. Data were extracted from the medical records, while magnetic resonance imaging scans and all laparoscopic surgery videos were retrospectively reviewed to assess the presence of the small intestine in the pelvic cavity as well as the adhesions at each site. Groups with and without the small intestine in the pelvic cavity, and those requiring a Trendelenburg angle above or below 13° were compared. RESULTS: In total, 219 patients were examined. The Trendelenburg angle was significantly higher (p = 0.004), while a significant increase in ovarian adhesions was observed (p = 0.033; odds ratio [OR], 2.30; 95% confidence interval [CI], 1.05-5.01) in the group without the presence of the small intestine in the pelvic cavity. Furthermore, the group requiring a Trendelenburg angle of ≥13° had significantly thicker subcutaneous fat (p = 0.044) and more ileal adhesions (p = 0.040, OR, 1.82; 95% CI, 1.03-3.23) than the group with an angle of <13°. CONCLUSION: Cases of ileal adhesions or thick subcutaneous fat are more likely to require a Trendelenburg angle of ≥13°. Therefore, Trendelenburg complications should be considered in this group. In addition, ovarian adhesions make it more difficult to exclude the small intestine from the small pelvic cavity, and may be associated with endometriosis.
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Procedimientos Quirúrgicos Ginecológicos , Intestino Delgado , Laparoscopía , Humanos , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Adulto , Adherencias Tisulares/etiología , Persona de Mediana Edad , Estudios Retrospectivos , Intestino Delgado/cirugía , Intestino Delgado/diagnóstico por imagen , Procedimientos Quirúrgicos Ginecológicos/métodos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Pelvis/cirugía , Inclinación de Cabeza/efectos adversosRESUMEN
AIM: Exclusion of polycystic ovarian morphology (PCOM) from the diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been proposed. We analyzed the profiles of adolescent women with suspected PCOS based on the Japan Society of Obstetrics and Gynecology (JSOG) diagnostic and Rotterdam criteria, excluding those with PCOM. METHODS: Thirteen- to twenty-one-year-old women with suspected or confirmed diagnosis of PCOS according to the JSOG and Rotterdam criteria were included in this study. Patient characteristics such as hormone levels and body mass index (BMI) were compared between the groups. Correlations between BMI and testosterone, and BMI and time to diagnosis were also analyzed. RESULTS: Twenty-nine patients were diagnosed with adolescent PCOS according to the JSOG criteria, and 11 patients according to the Rotterdam criteria after excluding the patients fulfilling the PCOM criteria. Serum testosterone levels were significantly higher in adolescents diagnosed with PCOS using the Rotterdam criteria than in those diagnosed using the JSOG criteria (p < 0.001). The obese group had significantly higher testosterone levels and a longer time from menarche to PCOS diagnosis. A positive correlation was observed between BMI and testosterone levels (r = 0.318, p = 0.014). CONCLUSION: Although adolescents with PCOS diagnosed using the Rotterdam criteria exhibited higher testosterone levels, which is a typical characteristic of this condition, the JSOG criteria may be useful for the early diagnosis of adolescent PCOS, including suspected cases. The differences between the two criteria may reflect the natural history of PCOS and its different reproductive and metabolic phenotypes.
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Índice de Masa Corporal , Síndrome del Ovario Poliquístico , Testosterona , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/sangre , Femenino , Adolescente , Testosterona/sangre , Adulto Joven , Ovario/patología , Ovario/diagnóstico por imagen , AdultoRESUMEN
Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.
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Ginecología , Obstetricia , Humanos , Japón , Femenino , Ginecología/normas , Obstetricia/normas , Sociedades Médicas/normas , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/terapia , Obstetras , GinecólogosRESUMEN
BACKGROUND: Assisted reproductive technology accounts for an increasing proportion of infertility treatments, and assessments to predict clinical pregnancy outcomes are desired. Extracellular vesicles exist in follicular fluid, and small non coding RNAs in extracellular vesicles underline the possibility of reflecting pregnancy potential. METHODS: Follicular fluid samples are collected from 20 ovarian follicles of 15 infertile patients undergoing assisted reproductive technology. Extracellular vesicles are isolated by serial centrifugation and small RNA sequencing is performed to investigate the profiles of microRNAs and P-element-induced wimpy testis-interacting RNAs. RESULTS: Small extracellular vesicles with a size range of approximately 100 nm are successfully isolated, and the small non coding RNA profiles of pregnant samples (n = 8) are different from those of non-pregnant samples (n = 12). Fourteen dysregulated small non coding RNAs are selected to identify the independent candidates [mean read count >100, area under the curve >0.8]. Among them, we find that a specific combination of small non coding RNAs (miR-16-2-3p, miR-378a-3p, and miR-483-5p) can predict the pregnant samples more precisely using a receiver operating characteristics curves analysis (area under the curve: 0.96). Furthermore, even in the same patients, the three microRNAs are differentially expressed between pregnant and non-pregnant samples. CONCLUSIONS: Our results demonstrate that small non coding RNAs derived from small extracellular vesicles in follicular fluid can be potential non-invasive biomarkers for predicting pregnancy, leading to their probable application in assisted reproductive technology. Further large-scale studies are required to validate the clinical usefulness of these small non coding RNAs.
Assisted reproductive technologies (ART) are medical procedures used to address infertility. Follicular fluid (FF)is a liquid that surrounds the immature egg cells (oocytes) and provides hormones and nutrients necessary for their maturation and eventual development into embryos. We analyzed genetic components within the FF as a potential predictor of reproductive outcomes following ART. Here, we show that a specific combination of genetic elements produced by the FF in successful pregnancies did not occur in unsuccessful pregnancies. Our findings may help to provide a non-invasive approach to determining reproductive outcomes during ART procedures.
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Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.
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Hipotiroidismo , Complicaciones del Embarazo , Resultado del Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiroxina , Humanos , Embarazo , Femenino , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/sangre , Tiroxina/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Tirotropina/sangre , Fertilidad/efectos de los fármacos , Aborto Espontáneo , Nacimiento PrematuroRESUMEN
BACKGROUND: We aimed to examine the effects of endometriosis on the rate of abnormal placentation by comparing the data of pregnant women with and without endometriosis. METHODS: A case-control study was conducted to compare the perinatal outcomes between women with and without endometriosis. In the subgroup analysis, magnetic resonance imaging (MRI) scans of pregnant women with placenta previa were used to measure the cervical angle and its relationship with endometriosis. The cervical angle was measured as the angle between the cervical glands and the line perpendicular to the spinal column in each sagittal MRI section. RESULTS: We retrospectively analyzed data from 3453 cases of singleton deliveries between 2015 and 2019 at two study facilities. Among them, 159 had clinically or surgically confirmed endometriosis. The odds ratio (OR) for abnormal placental position was significantly higher in pregnant women with endometriosis (OR. 2.82; 95% confidence interval [CI], 1.58-5.04). The OR was 3.21 (95% CI, 1.57-6.55) in the endometriosis-surgery group (91 patients) and 2.32 (95% CI, 0.91-5.88) in the non-surgery group (68 patients). Furthermore, 44 women who underwent pelvic MRI after 30 weeks of gestation were included to examine the cervical angle. Then, we compared the date of pregnant women with (n = 6) and without endometriosis (n = 38). Regardless of placental attachment position, the cervical angle was significantly lower in the group with than in the group without a history of endometriosis. CONCLUSION: Pregnant women with a history of endometriosis may have stronger uterine retroversion, which could potentially contribute to abnormal placental positioning.
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Endometriosis , Placenta Previa , Femenino , Embarazo , Humanos , Endometriosis/diagnóstico por imagen , Endometriosis/patología , Placenta/diagnóstico por imagen , Placenta/patología , Estudios de Casos y Controles , Estudios Retrospectivos , Placenta Previa/diagnóstico por imagenRESUMEN
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.
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Background: Primary ovarian insufficiency (POI) is characterized by the development of hypergonadotropic hypogonadism before 40 years of age and leads to intractable infertility. Although in vitro fertilization and embryo transfer with donated eggs enables pregnancy, not a few patients desire pregnancy using their oocytes. However, follicular development is rare and unpredictable in patients with POI. Thus, there is a need for treatments that promote the development of residual follicles and methods to accurately predict infrequent ovulation. Methods: This review discusses the effects of various treatments for obtaining eggs from POI patients. Furthermore, this study focused a potential marker for predicting follicular growth in patients with POI. Main Findings: Different treatments such as hormone-replacement therapy, dehydroepiandrosterone supplementation, platelet-rich plasma injection, and in vitro activation have shown varying degrees of effectiveness in retrieving oocytes from patients with POI. To predict follicle development in the cycle, elevated serum estradiol and reduced follicle-stimulating hormone (FSH) levels are important. However, these markers are not always reliable under continuous estradiol-replacement therapy. As a novel marker for predicting follicle growth, serum anti-Müllerian hormone (AMH) levels, measured using the picoAMH enzyme-linked immunosorbent assay, were found to predict follicle growth in patients and the cycle. Conclusion: This review highlights the challenges and available interventions for achieving pregnancy using a patient's oocytes in cases of POI. We believe that a combination of currently available treatments and prediction methods is the best strategy to enable patients with POI to conceive using their own eggs. Although AMH levels may predict follicle growth, further research is necessary to improve the chances of successful follicular development and conception in patients with POI.