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Aim: Endometriosis is a complex, multifactorial disease. Recent advances in molecular biology underscore that somatic mutations within the epithelial component of the normal endometrium, alongside aberrant epigenetic alterations within endometrial stromal cells, may serve as stimulators for the proliferation of endometriotic tissue within the peritoneal cavity. Nevertheless, pivotal inquiries persist: the deterministic factors driving endometriosis development in certain women while sparing others, notwithstanding comparable experiences of retrograde menstruation. Within this review, we endeavor to synopsize the current understanding of diverse pathophysiologic mechanisms underlying the initiation and progression of endometriosis and delineate avenues for future research., Methods: A literature search without time restriction was conducted utilizing PubMed and Google Scholar., Results: Given that aberrant clonal expansion stemming from cancer-associated mutations is common in normal endometrial tissue, only endometrial cells harboring mutations imparting proliferative advantages may be selected for survival outside the uterus. Endometriotic cells capable of engendering metabolic plasticity and modulating mitochondrial dynamics, thereby orchestrating responses to hypoxia, oxidative stress, inflammation, hormonal stimuli, and immune surveillance, and adeptly acclimating to their harsh surroundings, stand a chance at viability., Conclusion: The genesis of endometriosis appears to reflect the evolutionary principles of mutation, selection, clonal expansion, and adaptation to the environment., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: Artificial intelligence, especially ChatGPT, has been used in various aspects of medicine; however, whether ChatGPT can be used in case report writing is unknown. This study aimed to provoke discussion and provide a platform for it., Methods: I wrote a theoretical case report where cyst aspiration cured a twisted ovarian cyst (Manuscript 4). I tasked ChatGPT with generating case reports by inputting information at three different levels: (1) key message and case profile, (2) addition of key introduction information (including known facts and problems to be solved), and (3) further addition of main discussion points. These inputs resulted in the creation of Manuscripts 1-3, which were subjected to analysis. Manuscript 3, generated by ChatGPT with the deepest information input, was compared with Manuscript 4, the human-authored counterpart., Results: With the least information, Manuscript 1 can stand on its own, but its content is superficial. The more detailed data input, the more readable and reasonable the manuscripts become. A human-written manuscript involves personal experience and viewpoints other than obstetrics-gynecology., Conclusions: Better input produced more reasonable and readable case reports. Human-written paper, compared with ChatGPT-generated one, can involve "human touch." Whether such human touch enriches the case report awaits further discussion. Whether ChatGPT can be used in case report writing, and if it can, to what extent, should be worthy of further study. I encourage every doctor to form their own stance towards ChatGPT use in medical writing., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: ChatGPT's role in medical writing is a topic of discussion. I experimented whether ChatGPT almost automatically generates Correspondence or Letter addressed to a "translated" article, and thereby wish to arouse discussion regarding ChatGPT use in medical writing., Methods: I input an English article of mine into ChatGPT, tasking it with generating an English Disagreement Letter (Letter 1). Next, I tasked ChatGPT with translating the manuscript addressed to from English-French-Spanish-German. Then, I once again tasked ChatGPT with generating an English Disagreement Letter addressed to a German manuscript (triplicate translated manuscript) (Letter 2)., Results: Letters 1 and 2 are readable and reasonable, shooting the point that the author (myself) felt as the weakness of the article. Letters addressed to French (single translation) and to Spanish (double translation) and longer Letters (corresponding to Letters 1 and 2) are also readable, and thus stand., Conclusions: Solely based on this experiment, one may be able to write a letter even without understanding the meaning of the paper being addressed, let alone the language of the paper. Although this humble experiment does not conclude anything, I plea for a comprehensive discussion on the implications of these findings., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: The refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes frozen embryo transfer (FET) an alternative to fresh ET and has contributed to the success of assisted reproductive technology. Compared with fresh ET cycles, FET cycles were associated with better in vitro fertilization outcomes; however, the occurrence of pregnancy-induced hypertension, preeclampsia, and placenta accreta spectrum (PAS) was higher in FET cycles. PAS has been increasing steadily in incidence as a life-threatening condition along with cesarean rates worldwide. In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions., Methods: A literature search was performed in the PubMed and Google Scholar databases., Results: Risk factors associated with PAS incidence include a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling, and abnormally invasive trophoblasts, or a combination thereof. Freezing, thawing, and hormone replacement manipulations have been shown to affect multiple cellular pathways, including cell proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and mitochondrial function. Molecules involved in abnormal migration and EMT of extravillous trophoblast cells are beginning to be identified in PAS placentas. Many of these molecules were also found to be involved in mitochondrial biogenesis and dynamics., Conclusion: The etiology of PAS may be a multifactorial genesis with intrinsic predisposition (e.g., placental abnormalities) and certain environmental factors (e.g., defective decidua) as triggers for its development. A distinctive feature of this review is its focus on the potential factors linking mitochondrial function to PAS development., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: Contribution to the authorship, including that for case reports, should be appropriately evaluated. I have noticed a scarcity of case reports with clinic doctors listed as coauthors, prompting this investigation. I sought to offer suggestions on the possible reasons for this trend., Methods: I checked case reports published in the Journal of Obstetrics and Gynaecology Research, the Journal of Medical Case Reports, and the BMJ Case Reports. I identified case reports listing a clinic doctor as a coauthor. I consulted eight professors at Jichi Medical University to ascertain whether case reports from their departments included clinic doctors as coauthors and, if not, the reasons., Results: Among 65 case reports from Japanese institutes published in the Journal of Obstetrics and Gynaecology Research, only one paper lists a clinic doctor as a coauthor. Of 100 and 50 papers published in the Journal of Medical Case Reports and BMJ Case Reports, respectively, none listed a clinic doctor as a coauthor. Six out of eight professors admitted to never considering the idea of including clinic doctors as coauthors., Conclusions: The scarcity of case reports with clinic doctors as coauthors extends beyond Japanese obstetrics and gynecology, encompassing various specialties worldwide. Center doctors do not think of the idea that a clinic doctor should be a coauthor. A clinic doctor who transferred the patient should be considered as a candidate coauthor depending on his/her scientific contribution. Such an approach could foster an environment encouraging doctors to contribute to academic writing, regardless of their workplace., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its pathogenesis remains largely unknown. This review focuses on how androgen excess influences the molecular basis of energy metabolism, mitochondrial function, and mitophagy in granulosa cells and oocytes, summarizes our current understanding of the pathogenesis of PCOS, and discuss perspectives on future research directions., Methods: A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review., Results: Female offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5'-triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS., Conclusion: In conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy-apoptosis axis., (© 2024 Japan Society of Obstetrics and Gynecology.)

Aim: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan., Methods: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed. A questionnaire survey was also conducted to weigh each perinatal adverse event. For each of the nine outcomes, a restricted cubic spline model was made to estimate the association between the "expected gestational weight gain at 40 weeks" and the outcome risk., Results: Since the classes of medical facilities were generally the same, weights were assigned according to the mean of the questionnaires rather than by the class of the facility. For each pre-pregnancy BMI, the weight gains during pregnancy that minimized the predicted probability of various adverse perinatal events were 12-15, 10-13, 7-10, and upper limit of 5 kg for the underweight, normal-weight, obese 1, and obese ≥2 groups, respectively., Conclusions: The weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy BMI was established., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Aim: Endometriosis is a chronic disease of reproductive age, associated with pelvic pain and infertility. Endometriotic cells adapt to changing environments such as oxidative stress and hypoxia in order to survive. However, the underlying mechanisms remain to be fully elucidated. In this review, we summarize our current understanding of the pathogenesis of endometriosis, focusing primarily on the molecular basis of energy metabolism, redox homeostasis, and mitochondrial function, and discuss perspectives on future research directions., Methods: Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this narrative literature review., Results: Mitochondria serve as a central hub sensing a multitude of physiological processes, including energy production and cellular redox homeostasis. Under hypoxia, endometriotic cells favor glycolysis and actively produce pyruvate, nicotinamide adenine dinucleotide phosphate (NADPH), and other metabolites for cell proliferation. Mitochondrial fission and fusion dynamics may regulate the phenotypic plasticity of cellular energy metabolism, that is, aerobic glycolysis or OXPHOS. Endometriotic cells have been reported to have reduced mitochondrial numbers, increased lamellar cristae, improved energy efficiency, and enhanced cell proliferation and survival. Increased mitochondrial fission and fusion turnover by hypoxic and normoxic conditions suggests an activation of mitochondrial quality control mechanisms. Recently, candidate molecules that influence mitochondrial dynamics have begun to be identified., Conclusion: This review suggests that unique energy metabolism and redox homeostasis driven by mitochondrial dynamics may be linked to the pathophysiology of endometriosis. However, further studies are needed to elucidate the regulatory mechanisms of mitochondrial dynamics in endometriosis., (© 2023 Japan Society of Obstetrics and Gynecology.)

Aim: Tissue factor pathway inhibitor 2 (TFPI2) is a structural homolog of tissue factor pathway inhibitor 1 (TFPI1). Since TFPI2 is a placenta-derived protein, dynamic changes in TFPI2 levels may be related to pregnancy-related diseases. Furthermore, TFPI2 has been reported to be a novel serum biomarker for detecting ovarian cancer, especially clear cell carcinoma (CCC). This review aims to summarize the current knowledge on the biological function of TFPI2, highlight the major challenges that remain to be addressed, and discuss future research directions., Methods: Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this review. We also provide novel complementary information to what is known about the action of TFPI2., Results: Since TFPI2 concentrations in the blood of pregnant women, preeclampsia patients, and cancer patients vary greatly, its pathophysiological functions have attracted attention. Downregulation of TFPI2, a tumor-suppressor gene, by hypermethylation may contribute to the progression of several cancers. On the other hand, TFPI2 overexpressed in CCC is a risk factor for the development of thrombosis, possibly through inhibition of plasmin activity. However, agreement on the biological function of TFPI2 is still lacking and there are many scientific questions to be addressed. In particular, the lack of international standardization for the quantification of TFPI2 concentrations makes it difficult for researchers and clinicians to evaluate, pool, and compare data from different studies across countries., Discussion: This review summarizes current understandings and challenges in TFPI2 research and discusses future perspectives., (© 2023 Japan Society of Obstetrics and Gynecology.)

Aim: Tissue factor (TF), the primary initiator of the extrinsic coagulation pathway, contributes to the generation of a hypercoagulable and prothrombotic state in cancer patients. TF pathway inhibitor (TFPI) is a major inhibitor of TF-mediated coagulation pathway. The two proteins, TFPI1 and TFPI2, are encoded by separate genes. Indeed, various cancer patients with venous thromboembolism (VTE) had significantly lower TFPI1 levels than those without VTE. In contrast, serum TFPI2 level was found to increase in ovarian cancer patients with VTE. It remains unclear why TFPI2, unlike TFPI1, is elevated in ovarian cancer patients with VTE. The aim of this review is to explore the pathophysiological role of TFPI2 on the coagulation and fibrinolysis system., Methods: A literature search was performed from inception to April 30, 2022 in the PubMed and Google Scholar databases., Results: TFPI1 and TFPI2 are homologs with different protease inhibitory activities in the coagulation and fibrinolysis system. TFPI1 inhibits TF/factor VIIa (FVIIa) catalyzed factor X (FX) activation. On the other hand, TFPI2 is unlikely to affect TF-initiated thrombin generation, but it has strong inhibitory activity against plasmin. Plasmin is involved in fibrin degradation, clot lysis, and inactivation of several coagulation factors (such as FV, FVIII, FIX, and FX). TFPI2 may increase the risk of VTE by inhibiting plasmin-dependent fibrinolysis., Conclusion: TFPI1 and TFPI2 may have different key functions in regulating the coagulation and fibrinolytic systems., (© 2023 Japan Society of Obstetrics and Gynecology.)

Aim: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization., Methods: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization., Results: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications., Conclusion: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix., (© 2021 Japan Society of Obstetrics and Gynecology.)

Aims: The purpose of this study is to first investigate the correlation between image features and histological findings and the clinical severity of adenomyosis; second, search for imaging features to assess the type and locoregional extension of the disease; and finally, discuss the notation of image-based classification., Methods: This paper combines a review of the literature on adenomyosis with a series of cases who underwent surgery at Nara Medical University Hospital., Results: Currently, there has been a lack of clear, clinically relevant, and internationally acceptable definition and histological classification due to its diverse phenotype. A number of researchers have attempted to standardize the magnetic resonance imaging (MRI) features of adenomyosis. Some researchers have begun studies that relate the subtype classification using MRI to disease severity. There is evidence suggesting that diffuse adenomyosis and intrinsic adenomyosis are correlated with menstrual bleeding, while extrinsic adenomyosis and coexistence of deep infiltrating endometriosis (DIE) are related to pelvic pain. MRI-based classifications that are simple for use in the clinical setting are beginning to be proposed. However, the reliability and validity of these classifications have not yet been verified. A simplified notation is required to discuss the association between the classification and severity of adenomyosis. We introduce case reports using the notation of four items necessary for classification of adenomyosis., Conclusion: There is an urgent need to determine the definitions of terms used in subtype classification and to create and validate a globally unified notation that can predict the severity of adenomyosis symptoms., (© 2021 Japan Society of Obstetrics and Gynecology.)

Aim: Our aim was to examine whether serum levels of placental growth factor (PlGF) and soluble endoglin (sEng) at 19-25 and 26-31 weeks of gestation were associated with the occurrence of the 9-block categorization of placenta weight (PW) and fetal/placenta ratio (F/P ratio)., Methods: We performed a retrospective cohort study in 1391 women with singleton pregnancy. Serum levels of PlGF and sEng were measured by enzyme immunosorbent assay. A light placenta was defined as PW ZS < -1.28 SD. Based on the PW (light, normal, and heavy) and F/P ratio (relatively heavy, balanced growth, and relatively small), 9-block categorization were performed. Multivariable logistic regression analyses were performed., Results: Low PlGF at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block A (light placenta and relatively heavy infant), after adjusting for prepregnancy body mass index and serum levels of sEng. High sEng at 26-31 weeks was an independent risk factor for the birth of infants belonging to Block D (light placenta and balanced growth of infant), after adjusting for past history of either preeclampsia or gestational hypertension, high pulsatility index of uterine artery flow velocity waveforms in the second trimester, and serum level of PlGF., Conclusions: Low PlGF levels at 26-31 weeks of gestation may precede a light placenta and relatively heavy infant (Block A), and high sEng levels at 26-31 weeks of gestation may precede a light placenta and balanced growth of infant (Block D)., (© 2021 Japan Society of Obstetrics and Gynecology.)

Aim: We examined whether critical conditions, which were defined as having hemoglobin (Hb) less than 7.0 g/dL, shock index ≥1.0, or need for transfusion, were associated with the presence of extravasation (EV) on dynamic computed tomography (CT) in women with late post-partum hemorrhage (PPH)., Methods: Forty post-partum women with late PPH without evident retained products of conception performed dynamic CT. Two radiologists retrospectively evaluated dynamic CT, and determined the presence or absence of EV and a sac-like structure within the uterine cavity with enhancement., Results: Ultrasound images were available in 34/40 patients. Color Doppler flow in uterine cavity was evaluated in 33/34 (97%), and all women showed abnormal flow. Of 40 patients, dynamic CT revealed EV in 8 (20%), and a sac-like structure in 30 (75%). Thus, we diagnosed these 38 (95%) as having uterine artery pseudoaneurysm (UAP). Uterine artery embolization was performed in 36/38 diagnosed as having UAP, and in 2/2 patients with an unknown cause of hemorrhage. The incidence rates of critical conditions were significantly increased in PPH women with than without EV on dynamic CT: Hb <7.0 g/dL (62.5 vs 0%, [P < 0.001]), shock index ≥1.0 (50 vs 9.4% [P = 0.020]), and need for transfusion (37.5 vs 0% [P = 0.006]). Abnormal color Doppler flows were observed in all patients with either EV and sac on dynamic CT., Conclusion: Dynamic CT was useful for diagnosing UAP, and for evaluating critical conditions, in women with late PPH not complicated by retained products of conception., (© 2020 Japan Society of Obstetrics and Gynecology.)

Aim: To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed., Methods: Cases of uterine rupture recorded for a period of 5 years were included., Results: There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30-32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases., Conclusion: This survey revealed the current incidence of uterine rupture in Japan., (© 2019 Japan Society of Obstetrics and Gynecology.)

Aim: To compare serum levels of angiogenesis-related factors between 14 women with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome and a woman with acute fatty liver of pregnancy (AFLP)., Methods: Serum samples were collected in 2004-2008 and 2013-2016. The levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured by an automated electrochemiluminescence immunoassay using Elecsys sFlt-1 and Elecsys PlGF. After logarithmic transformation, levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio in a woman with AFLP were compared with those in women with HELLP syndrome, using the one-sample t-test., Results: At 37 weeks of gestation, a patient was diagnosed with AFLP based on Swansea criteria (showing six features including elevated transaminases), and she also showed a duodenal ulcer with active bleeding, thrombocytopenia and hypertension. Her serum levels of sFlt-1 and sFlt-1/PlGF ratio were significantly higher than in those with HELLP syndrome (273 040 pg/mL vs 15 135 [mean], P < 0.001; 4236 vs 224, P < 0.001; respectively). However, her serum level of PlGF was not significantly different from those with HELLP syndrome., Conclusion: Serum levels of sFlt-1 and the sFlt-1/PlGF ratio, but not PlGF, in a woman with AFLP were markedly higher than those in women with HELLP syndrome. AFLP may be a different clinical entity from HELLP syndrome based on angiogenesis-related factors. Clinically, the sFlt-1/PlGF ratio may be used to rapidly distinguish AFLP from HELLP syndrome., (© 2018 Japan Society of Obstetrics and Gynecology.)