An algorithm for the pre-operative differentiation of benign ovarian tumours based on magnetic resonance imaging interpretation in a regional core hospital: A retrospective study.

Objective: For selecting minimally invasive surgery (i.e. laparoscopic ovarian cystectomy) for treating ovarian tumours (OTs) in premenopausal patients, the pre-operative differentiation of benign ovarian tumours (Be-OTs) based on magnetic resonance imaging (MRI) interpretation is important. This paper describes the authors' 8-year experience of approximately 1000 OT cases, and provides information about a diagnostic algorithm to help other hospitals. Study design: The medical records of 901 patients aged < 50 years with OTs from 1 January 2015-31 March 31 2023 were reviewed. First, the accuracy of pre-operative differentiation between Be-OTs and borderline/malignant ovarian tumours (Bo/Ma-OTs) was compared in each type of OT. Second, to identify the factors influencing differentiation between Be-OTs and Bo/Ma-OTs in 164 serous/mucinous ovarian tumours (SM-OTs), a multi-variate logistic regression analysis was performed to assess the effect of 13 factors, including MRI findings, OT size and tumour markers. Results: In the comparison of diagnostic accuracy of pre-operative MRI for each OT type, accuracy was found to be notably high for ovarian endometrial cyst (OEC) (n = 409), ovarian mature cystic teratoma (OMCT) (n = 308), ovarian endometrioid adenocarcinoma (OEA) (n = 6) and ovarian clear cell adenocarcinoma (OCCA) (n = 14). On the other hand, discrepancies between MRI and pathological findings often occurred in SM-OTs, including ovarian serous cystadenoma (n = 86), ovarian mucinous adenocarcinoma (n = 61), ovarian serous adenocarcinoma (n = 12) and ovarian mucinous adenocarcinoma (n = 5). In the multi-variate logistic regression analysis of the latter 164 patients, in addition to MRI findings, OT size and carbohydrate antigen 125 also had an effect to some extent. The combination of MRI interpretation and OT size may enhance differentiation of Be-OTs and Bo/Ma-OTs. Conclusions: Among four types of OTs (OEC, OMCT, OEA and OCCA), MRI interpretation was able to differentiate between Be-OTs and Bo/Ma-OTs almost perfectly. Additionally, to mitigate the difficulty in differentiating SM-OTs, OT size may be useful in combination with MRI findings, although further accumulation and analysis of OT cases is needed.

Obvious advantage of vaginal natural orifice transluminal endoscopic surgery hysterectomy against total laparoscopic hysterectomy in small uterus patients and the future prospects at a regional core institution: A retrospective study.

Objective: Owing to the combination of benefits, including permanent visual guidance and no abdominal skin incision, vaginal natural orifice transluminal endoscopic surgery hysterectomy (vNOTES-H) is currently widely used. However, the introduction of vNOTES-H has been delayed in many Japanese regional core hospitals because of its specific device and skill requirements. Therefore, the characteristics and advantages should be explained for the widespread use of this technique. Study design: We reviewed the medical records of 17 patients with vNOTES-H and 94 patients with total laparoscopic hysterectomy (TLH) from January 1, 2015 to December 31, 2022. In this analysis, to compare the results of vNOTES-H to TLH, we excluded certain patients with a relatively heavy uterus (>255 g) and the presence of abdominal adhesions. In this report, first, the characteristics of the vNOTES-H procedures using a transvaginal access platform are explained by referring to one representative patient. Second, the patient characteristics of the vNOTES-H and TLH groups, including operation time and blood loss amount, were compared. Then, to detect the influence of vNOTES-H on the difficulty of operation among all 111 patients, we performed a multivariate logistic regression analysis to assess the influence of each of 9 factors, including "vNOTES-H", "Advanced age", "High BMI", "3 parity", "Gynaecological operation history", "Adenomyoma", "Large leiomyoma", "Heavy uterus" and "Large uterus", on the two indexes, including "Short time operation" and "Massive blood loss". Results: In the simple comparison between the groups with vNOTES-H and TLH, the operation time in the former group was significantly shorter than in the latter group, although other factors did not show significant differences, including blood loss amount. Moreover, in the multivariate logistic regression analysis of all 111 patients, the "vNOTES-H" factor showed a significantly high possibility of "short time operation", although no factor, including "vNOTES-H", showed a significant influence on "massive blood loss". Conclusions: vNOTES-H showed advantages in terms of operation time without increasing blood loss for patients with a relatively small uterus. However, to expand the selection for vNOTES-H, we should accumulate further patients and perform more analyses.

Transcriptomic analysis of feeder-free culture system for maintaining naïve-state pluripotency in human pluripotent stem cells.

Background: Human pluripotent stem cells (hPSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (PSCs) have the capacity of self-renewal and multilineage differentiation in vitro. Conventional hPSCs, which are in a primed state, can produce various types of differentiated cells. However, the variability in their degree of pluripotency and differentiation propensities, which is influenced by the inductive methods and culture conditions, limit their availability. Therefore, PSCs in a naïve state are a promising source of PSCs. Methods: We recently developed a culture system for naïve hPSCs using an inhibitor of the NOTCH signaling pathway and a histone H3 methyltransferase disruptor. This culture system requires feeder cells for stably maintaining the naïve hPSCs. We aimed to develop a culture system for hPSCs that could maintain pluripotency under feeder-free conditions. Results: We used two inhibitors to develop an alternative feeder-free culture system to obtain naïve hPSCs. The naïve cells underwent stable cellular proliferation and were positive for naïve stem cell markers; in addition, they could differentiate into the three germ layers. These feeder-free dome-shaped induced pluripotent stem cells (FFDS-iPSCs) have characteristics similar to that of naïve-like PSCs. Conclusions: The naive hPSCs under feeder-free conditions could ensure supply of cells for various applications in regenerative medicine and disease modeling.

Comparison of robotic-assisted laparoscopic hysterectomy to total laparoscopic hysterectomy in terms of operational complications at a regional institution: A retrospective study.

Objective: With the increased use of total laparoscopic hysterectomy (TLH), the use of robotic-assisted laparoscopic hysterectomy (RALH) has increased due to its technical advantages. On the other hand, RALH has some disadvantages, including its high cost, which includes not only the purchase price of robotic technology systems but also the running cost and long preparation time for setting assistant robots. Therefore, an overall understanding of the characteristics of RALH is needed. Study design: We reviewed the medical records of 432 patients with TLH and 93 patients with RALH from January 1, 2015, to December 31, 2022. In this analysis, we excluded certain cases with concomitant laparoscopic cystectomy (LC) and a heavy uterus (> 400 g). First, the patient characteristics of the TLH and RALH groups, including operation time and blood loss amount, were compared. Then, among these cases, we sought to predict difficult cases for TLH and RALH by identifying risk factors related to each of the following three categories of operational complications: "long operation time", "massive blood loss" and "other complications". For this purpose, multivariate logistic regression analyses were performed to assess the influence of each of 7 representative factors, namely, "advanced age", "high body mass index (BMI)", "nulliparity", "concomitant pelvic lymphadenectomy (PLA)", "heavy uterus", "abdominal adhesion", and "large leiomyoma". Results: In the simple comparison without various factors, there was an advantage of RALH in both the average operation time and blood loss amount. However, in the multivariate logistic regression analyses, a significant risk was detected in the following relationships: 1) between "long-term operation" and "abdominal adhesion" and 2) between "other complications" and "heavy uterus". Conclusions: RALH has sufficient advantages over TLH regarding at least in terms of blood loss amount; however, since RALH may have potential weaknesses in the context of complex cases, additional cases and analyses are needed.

Preventive effect of metronidazole vaginal tablets on vaginal bacteria-related postoperative complications with total laparoscopic hysterectomy.

BACKGROUND: The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis. METHODS: We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others. RESULTS: In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate. CONCLUSIONS: The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy.

The effect of temporary uterine artery ligation on laparoscopic myomectomy to reduce intraoperative blood loss: A retrospective case-control study.

Objective: To reduce intraoperative blood loss in laparoscopic myomectomy, uterine artery occlusion or temporary uterine artery clipping have been employed. Recently, in addition to these techniques, temporary uterine artery ligation has been reported as a new method that has less invasive effects on fertility and needs no special devices to be used. This study aimed to evaluate the effect of temporary uterine artery ligation to minimize intraoperative blood loss during laparoscopic myomectomy. Study Design: This was a retrospective case-control study at the department of Obstetrics and Gynaecology, University Hospital Mizonokuchi, Teikyo University School of Medicine. A total of 264 patients with uterine leiomyoma who underwent laparoscopic myomectomy were enrolled in this study. We divided the patients into two groups, those who underwent temporary uterine artery ligation (52 patients) and those who did not (212 patients) and compared the operation time, blood loss volume, and other indexes. Second, to identify influential factors, we assessed the effects of 11 representative factors on massive blood loss or a prolonged operation time using multivariate analysis. Results: The intraoperative blood loss volume was decreased by approximately half with the addition of temporary uterine artery ligation (75.1 ± 73.6 ml vs. 158.5 ± 233.2 ml, p = 0.011), but the operation time was longer (200.5 ± 46.9 min vs. 160.1 ± 51.3 min, p < 0.001). Among the 264 patients, 25 patients (9/52 in the case group and 16/212 in the control group) had a prolonged operation time (≥ 240 min), and 24 patients (1/52 in the case group and 23/212 in the control group) experienced massive blood loss (≥ 400 ml). In the multivariate analysis, high body mass index, concomitant surgery and temporary uterine artery ligation showed a positive association with a prolonged operative time, and the presence of single leiomyoma showed a negative association. Concomitant surgery and the presence of large leiomyoma showed a positive association with massive blood loss, and temporary uterine artery ligation showed a negative association. Conclusions: By performing temporary uterine artery ligation during laparoscopic myomectomy, the volume of intraoperative blood loss could be decreased, especially in patients with large leiomyomas. However, because this procedure prolongs the operation time, there is still room for improvement.

Unilateral uterine artery embolization and Bakri tamponade balloon insertion in the treatment of acute puerperal uterine inversion: a case report.

BACKGROUND: Acute puerperal uterine inversion is rare but may cause massive postpartum blood loss due to uterine atony. Therefore, these patients must be diagnosed, and uterine replacement must be performed as soon as possible. However, in some cases, active bleeding due to uterine atony becomes uncontrollable, even though the uterine inversion itself is treated. In these cases, additional treatments, including surgical procedures, are needed. CASE PRESENTATION: A 41-year-old Japanese woman, gravida 1, para 0, was hospitalized for labor induction at 40 weeks and 3 days of gestational age. She had a vacuum-assisted delivery after 3 days of oxytocin administration, but acute uterine inversion occurred. Although replacement of the inverted uterus was successful by manual repositioning and Bakri balloon tamponade insertion, massive postpartum hemorrhage caused by uterine atony became uncontrollable. In this situation, since disseminated intravascular coagulation had developed, we used uterine artery embolization to stop the bleeding. After detecting the pseudo-aneurysmal sac and tortuous vessels of the right uterine artery, transcatheter right-sided uterine artery embolization was performed. Thirteen days after uterine artery embolization, she was discharged with no complications. CONCLUSIONS: In cases of disseminated intravascular coagulation caused by massive postpartum bleeding, uterine artery embolization may often be selected. In our case, since we performed angiography to detect the main bleeding site, the hemorrhage could be stopped with unilateral uterine artery embolization alone, without hysterectomy.

Successful Management of a Noncommunicating Rudimentary Uterine Horn Pregnancy by Laparoscopic Surgery: A Case Report and Literature Review.

Pregnancy in a noncommunicating rudimentary horn is extremely rare but can cause serious clinical complications, such as uterine rupture. The standard treatment is excision of the rudimentary horn, and recently, in some cases, laparoscopic resection has been performed in the first trimester of gestation. Herein, we present a case of noncommunicating rudimentary horn pregnancy (NCRHP), which was diagnosed by magnetic resonance imaging at 6 weeks of gestation and treated by laparoscopic surgery. However, we have also found some rare cases in which patients could obtain live newborn babies. Since management is affected by the different levels of obstetric medical care and diagnostic tools, we also performed a review and analysis of NCRHP. A PubMed search yielded 103 cases reported in the English literature. Correct diagnosis and laparoscopic treatment were achieved more frequently in developed countries, especially in the first trimester of gestation. On the other hand, symptoms, including abdominal pain and hypovolemic shock, tended to occur in the second trimester of gestation. This period was also found to be a risk factor for uterine rupture. Among 18 patients at the third trimester of gestation, 13 obtained live neonatal infants. Therefore, detailed information about this disease is crucial for proper treatments.

Predictive factors of spontaneously regressed uterine endometrial polyps during the waiting period before hysteroscopic polypectomy.

BACKGROUND: The presence of uterine endometrial polyps is associated with not only abnormal uterine bleeding but also infertility, so the use of hysteroscopic polypectomy has been increasing. This operation is considered to increase cost-effectiveness when performed prior to infertility treatments. However, there are typical problems to consider, including the possibility of spontaneous regression of the polyp and the duration of complete endometrial wound healing after surgery. Meaningless interventions must be avoided, when possible. Therefore, data acquisition and analysis of various findings obtained from surgery have become important for improving treatment procedures and patient selection. To estimate the spontaneous regression rates and contributions of multiple factors to uterine endometrial polyps during the waiting period (approximately 2-3 months) before hysteroscopic polypectomy, we performed a multivariate analysis of data from the records in our hospital. METHODS: The medical records of 450 cases from September 2014 to April 2021 in our hospital were retrospectively reviewed under the approval of our Institutional Review Board. We included all cases of hysteroscopic polypectomy with postoperative pathological diagnosis. We defined cases as having a "spontaneously regressed polyp" when the target polyp was not detected by postoperative pathological examination. We extracted data on the following ten factors: "Advanced age" (≥ 42 years), "Small polyp" (< 10 mm), "High body mass index" (≥ 25 kg/m2), "Nulliparity," "Single polyp," "Infertility," "Hypermenorrhea," "Abnormal bleeding," "No symptom," and "Hormonal drug use." We also classified cases into five groups according to the size of the polyp (≤ 4.9 mm, 5.0-9.9 mm, 10.0-14.9 mm, 15.0-19.9 mm, and ≥ 20.0 mm) and determined the frequency of spontaneously regressed polyp in each group. RESULTS: After exclusion of cases with insufficient data or other diseases, such as submucosal leiomyoma, 424 cases were analyzed. Among them, 28 spontaneously regressed polyps were identified, and the highest frequency of spontaneously regressed polyp was detected among the cases with polyps measuring 5.0-9.9 mm (16.4%). On multivariate analysis of the ten factors, "Small polyp" and "Hormonal drug use" were found to significantly impact the frequency of spontaneously regressed polyp. CONCLUSIONS: On the basis of the factors identified in this analysis, the indications for observation or medical therapy adapted to small polyps might be expanded.

Utility of a minimal skin incision technique for abdominal hysterectomy at a regional core hospital: a retrospective study.

BACKGROUND: We present a minimal skin wound abdominal hysterectomy for patients with leiomyomas and describe the characteristics of this technique. The skin wound was made as small as possible, with a maximum length of 6 cm. METHODS: In addition to introducing minimal skin wound abdominal hysterectomy, we retrospectively analyzed the medical records of 82 patients treated with minimal skin wound abdominal hysterectomy exclusively by two experts at Maruyama Memorial General Hospital between January 2013 and December 2016. Relationships between the leiomyoma characteristics and the difficulty of this operation, as estimated by operation time and blood loss, were statistically investigated. RESULTS: First, we introduce a case in which we performed minimal skin wound abdominal hysterectomy on a 46-year-old Japanese patient with multiple leiomyomas (maximum 8 cm in diameter). Then, we assessed the impacts of the leiomyoma characteristics on the difficulty of this operation. On multivariate analysis, the number of leiomyomas significantly affected operation difficulty. Other characteristics of the target leiomyoma showed no effect. Additionally, higher body mass index also made the operation more difficult. CONCLUSIONS: Although multiple leiomyomas can make this procedure difficult, minimal skin wound abdominal hysterectomy is safe and effective for use in many cases.

A retrospective study of 323 total laparoscopic hysterectomy cases for various indications and a case report treating caesarean scar pregnancy.

BACKGROUND: The application of laparoscopic surgeries has been increasing, and various uterine diseases in addition to leiomyoma/adenomyoma have become indications for total laparoscopic hysterectomy (TLH). Therefore, data acquisition and analysis of TLH procedures, including TLH for rare uterine diseases, have become important for improving surgical procedures and patient selection. To determine the prevalence of and risk factors for the occurrence of intraoperative and postoperative complications of TLH, we performed a multivariate analysis of the records in our hospital. METHODS: We retrospectively reviewed the medical records of 323 patients who underwent TLH for the treatment of leiomyoma/adenomyoma (278 cases), low-grade (pre)malignant uterine tumours (40 cases) and other rare uterine diseases (5 cases) from January 1, 2015, to December 31, 2019. Of the rare uterine diseases, one case of caesarean scar pregnancy for which TLH was performed is introduced as a case report. To assess the effects of 11 representative factors, including patient characteristics, uterus and leiomyoma sizes, indications for TLH and others, we performed a multivariate logistic regression analysis. RESULTS: Among the 323 cases, 20 intraoperative complications and 15 postoperative complications were reported. In the multivariate analysis, "ovarian tumour" and "heavy uterus" were positively associated and "nulliparity" was negatively associated with intraoperative complications. There were no significant risk factors for postoperative complications. The only risk factor for operative complications directly related to the resected uterus was "heavy uterus". Therefore, we could perform TLH relatively safely for patients with other indications besides leiomyoma/adenomyoma. CONCLUSIONS: Considering the factors detected in this analysis, the indications for TLH may be expanded. Owing to the increase in TLH for indications other than leiomyoma/adenomyoma, a more accurate determination of the treatment approach can be achieved.

The combination of dibenzazepine and a DOT1L inhibitor enables a stable maintenance of human naïve-state pluripotency in non-hypoxic conditions.

Conventional human pluripotent stem cells (hPSCs), known for being in a primed state, are pivotal for both basic research and clinical applications since such cells produce various types of differentiated cells. Recent reports on PSCs shed light on the pluripotent hierarchy of stem cells and have promoted the exploration of new stem cell states along with their culture systems. Human naïve PSCs are expected to provide further knowledge of early developmental mechanisms and improvements for differentiation programmes in the regenerative therapy of conventionally primed PSCs. However, practical challenges exist in using naïve-state PSCs such as determining the conditions for hypoxic culture condition and showing limited stable cellular proliferation. Here, we have developed new leukemia inhibitory factor dependent PSCs by applying our previous work, the combination of dibenzazepine and a DOT1L inhibitor to achieve the stable culture of naïve-state PSCs. The potential of these cells to differentiate into all three germ layers was shown both in vitro and in vivo. Such new naïve-state PSCs formed dome-shaped colonies at a faster rate than conventional, primed-state human induced PSCs and could be maintained for an extended period in the absence of hypoxic culture conditions. We also identified relatively high expression levels of naïve cell markers. Thus, non-hypoxia treated, leukemia inhibitory factor-dependent PSCs are anticipated to have characteristics similar to those of naïve-like PSCs, and to enhance the utility value of PSCs. Such naïve PSCs may allow the molecular characterization of previously undefined naïve human PSCs, and to ultimately contribute to the use of human pluripotent stem cells in regenerative medicine and disease modelling.

Significant risk factors for malignant transformation of ovarian endometrioma during dienogest treatment: a case report and retrospective study.

BACKGROUND: To determine the prevalence of and risk factors for malignant transformation of ovarian endometrioma during dienogest therapy, which is very rare, we examined multiple cases of malignant transformation of ovarian endometrioma during dienogest therapy and performed a multivariate analysis of the records in our hospital. METHODS: The medical records of 174 patients who underwent DNGT for the treatment of OMA from June 1, 2011, to May 31, 2018, were reviewed retrospectively with the approval of the Human Ethical Committee of the University of Teikyo Hospital. And we provided one representative case of MT with obtaining written informed consent. To assess the effects of six representative factors, including advanced age, parity, surgical history, and endometrial cyst characteristics (including 3 factors), on the possibility of malignant transformation, we performed a multivariate logistic regression analysis. RESULTS: Of the 174 cases, 4 were diagnosed with malignant transformation, and these cases are reported. In the multivariate analysis, advanced age (P = 0.0064), nullipara (P = 0.0322), and enlargement (P = 0.0079) showed significant differences for malignant transformation occurrence. All 4 malignant transformation cases were among the 19 patients who had all of these 3 factors. CONCLUSIONS: For a more accurate determination of the treatment approach, a larger sample size will be needed to determine the risk factors for malignant transformation during dienogest therapy.

Activation of Nrf2/Keap1 pathway by oral Dimethylfumarate administration alleviates oxidative stress and age-associated infertility might be delayed in the mouse ovary.

BACKGROUND: Age-associated infertility is a problem worldwide, and management of oxidative stress is known to be essential. Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway works as an essential defense mechanism against oxidative stress, and an oral drug Dimethylfumarate (DMF) is known to activate the pathway. METHODS: We tested the hypothesis that oral DMF could alleviate oxidative stress in the ovary, resulting in salvation of age-associated infertility in a mouse model of reproductive age, and we examined the effects of DMF administration. 20 mg/kg DMF was administrated to female mice from 32 to 48 weeks, and Nrf2 levels, antioxidant levels, ovarian reserve, DNA damage, and oxidative stress were examined. RESULTS: DMF administration resulted in elevated mRNA and protein levels of Nrf2, antioxidants, and telomere, and serum levels of Nrf2 and anti-mullerian hormone were also elevated. Results of TUNEL assay and Immunohistochemistry of mice ovarian tissues showed that DNA damage and oxidative stress were decreased by DMF administration, and significantly more oocytes were collected along with preservation of 60% more primordial follicles. CONCLUSIONS: Our data suggest that DMF administration activates the Nrf2/Keap1 pathway, elevate levels of antioxidants, and decrease DNA damage and oxidative stress, resulting in improved ovarian reserve in the mouse ovary.

The efficacy of non-assisted reproductive technology treatment might be limited in infertile patients with advanced endometriosis in their 30s.

AIM: To determine the efficacious treatment for infertile couples, we assessed the impact of infertility factors including endometriosis on assisted reproductive technology (ART) and non-ART treatment, and the effect of age in infertility treatment outcomes was also investigated. METHODS: The medical records of 1864 females, infertile patients from January 2000 to December 2015 at our hospital, were retrospectively reviewed under the approval of the Institutional Review Board. We extracted 10 representative factors and calculated the cumulative live birth rate (CLBR) in these patients. Multivariate analysis of ART and non-ART treatment was performed to assess the impact of infertility factors, and the age-related decline in cumulative live birth rate was calculated by creating eight age-stratified subgroups. RESULTS: In total, 21.9% and 49.4% of the patients conceived after being treated with non-ART and ART, respectively. Multivariate analysis revealed that age > 35, advanced endometriosis defined by the revised American Society for Reproductive Medicine classification system stages III to IV, and the past history or current presence of uterine fibroid had significantly negative impact on the outcome of non-ART. Age stratification revealed that advanced endometriosis adversely affected the outcome of non-ART, especially for patients in their 30s. Assisted reproductive technology treatment for patients with advanced endometriosis was shown to be efficacious because the negative impact had been diminished. CONCLUSION: Considering that non-ART treatment had limited role in patients with advanced endometriosis, prompt initiation of ART in these patients aged as young as 30 years can be recommended to achieve conception.

Prediction of the operative time for hysteroscopic myomectomy for leiomyomas penetrating the intramural cavity using leiomyoma weight and clinical characteristics of patients.

PURPOSE: To preoperatively predict the operative time (OT) for hysteroscopic myomectomy for G1 or G2 leiomyoma based on leiomyoma weight. METHODS: The data from 544 patients who underwent one-step hysteroscopic myomectomy were analyzed retrospectively. A total of 340 patients with leiomyoma penetrating the intramural cavity were identified as suitable candidates for calculation of the OT based on leiomyoma weight; we considered leiomyoma weight to be the most objective parameter for evaluating leiomyoma tissues. Additionally, 460 patients with a single leiomyoma were analyzed to estimate the weight of the resected leiomyoma based on its diameter. RESULTS: Considering total leiomyoma weight (TLW) and two additional coefficients (1.5: G2 leiomyoma, 0.75: vaginal parity of the patient), we demonstrated that our formula correlated well with OT (R 2 = 0.72). TLW also correlated well with the cube of the average diameter (AD) of leiomyomas (R 2 = 0.89). Predicting TLW significantly improved the application of specific coefficients depending on its value (1.0: AD 0.1-2.0 cm, 0.8: AD 2.1-3.0 cm, 0.7: AD 3.1-5.7 cm). CONCLUSION: The OT for hysteroscopic myomectomy of intracavital leiomyoma can be predicted prior to surgery using simple clinical information of the target leiomyoma and the patient.

Utility of a minimal skin incision laparotomy technique for removing uterine leiomyomas at a regional core hospital: a retrospective study.

BACKGROUND: We present a minimal skin wound abdominal myomectomy performed in our hospital and attempt to identify the optimal range of this technique by considering the characteristics of target leiomyomas. In this procedure, we attempted to make the skin wound as small as possible, with a maximum length of approximately 5 cm. METHODS: In addition to introducing the minimal skin wound abdominal myomectomy, we retrospectively collected and analyzed the medical records of 76 patients treated with minimal skin wound abdominal myomectomy exclusively by the same physician at Maruyama Memorial General Hospital between January 2007 and December 2016. We statistically investigated relationships between ten factors, including body mass index; patient's age; patient's parity; administration of gonadotropin-releasing hormone analogue; presence of anemia; the uterine leiomyomas' number, size, weight, and location; operation time; and blood loss. RESULTS: First, we introduce a case in which we performed minimal skin wound abdominal myomectomy for a 36-year-old Japanese patient with a large leiomyoma (10 cm in diameter). Then, we assessed the impacts of patient characteristics and leiomyoma characteristics on operation time and blood loss for this surgical method. In a multivariate analysis, only the number of resected leiomyomas significantly affected massive bleeding. Other factors showed no difference on operation time and the amount of blood loss. CONCLUSIONS: Minimal skin wound abdominal myomectomy is safe and effective for use in many patients, because only the number of leiomyomas affects the amount of blood loss. No other factor affected operation time. We suggest the possibility that the expanded use of minimal skin wound abdominal myomectomy may reduce the number of patients waiting for long periods to undergo laparoscopic surgery and may optimize the use of medical resources in rural areas.

Endophytic-Type Endometrial Cancer with Adenomyosis Successfully Diagnosed with Hysteroscopic Endometrial Biopsy Using an 8.3-mm Operative Resectoscope: A Case Report.

In order to diagnose endometrial cancer preoperatively, outpatient endometrial biopsy with a curette is frequently performed owing to its convenience. However, in some cases, gynecologists fail to diagnose endometrial cancer via outpatient endometrial biopsy because of the cancer's distribution in the uterus and its consistency. A 57-year-old Japanese woman (gravida 4 para 4) presented with a 6-month history of light but intermittent postmenopausal vaginal bleeding. A malignant uterine tumor was strongly suspected after imaging using ultrasound examination and magnetic resonance imaging; however, a precise pathological diagnosis was not achieved despite multiple outpatient endometrial biopsies with the aid of office hysteroscopy. Based on an endometrial biopsy obtained using a cutting loop electrode on an 8.3-mm operative resectoscope, we reached a diagnosis of endophytic-type endometrial cancer, which is in accordance with the final pathological diagnosis after abdominal hysterectomy. Three months after her first visit to our hospital, total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic/para-aortic lymph node dissection were performed. Macroscopically, the endometrium was atrophic, and there was no obvious mass in the uterine cavity; however, microscopically, the cancer cells mainly existed in the deep myometrium and the final diagnosis was International Federation of Gynecology and Obstetrics (FIGO) stage IB endometrial cancer. Operative biopsy of the uterine endometrium and deep myometrium using hysteroscopy confirmed an accurate preoperative diagnosis of uterine endometrial cancer specifically of the endophytic type.

Activation of Nrf2 might reduce oxidative stress in human granulosa cells.

Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is one of the most important defense mechanisms against oxidative stress (OS). It is well documented that equilibration status of OS plays fundamental roles in human reproductive medicine, and the physiological role of Nrf2 in ovarian granulosa cells (GCs) has not been determined yet. Herein we aimed to study the function of Nrf2 in GCs. Human ovarian tissues were subjected to immunohistochemistry to localize Nrf2 and Keap1 and we detected the expression of Nrf2 and Keap1 in the human GCs. Human luteinized GCs were isolated and cultured, and hydrogen peroxide (H2O2) or Dimethylfumarates (DMF), an activator of Nrf2, were added to GCs to analyze the relationship between Nrf2 and antioxidants by quantitative RT-PCR. The mRNA levels of Nrf2, catalase, superoxide dismutase 1 (SOD1), and 8-Oxoguanine DNA glycosylase (OGG1) were elevated by H2O2, and DMF treatment showed similar but pronounced effects through activation of Nrf2. To determine the relationship of Nrf2 and the generation of antioxidants, siRNAs were used and quantitative RT-PCR were conducted. Decreased expression of Nrf2 resulted in a decreased level of these antioxidant mRNA. Intracellular levels of ROS were investigated by fluorescence of 8-hydroxy-2'-deoxyguanosine and fluorescent dye, 2',7'-dichlorodihydrofluorescein diacetate after H2O2 and/or DMF treatment, and DMF treatment quenched intracellular ROS generation by H2O2. These results show that activation of Nrf2 might lead to alleviate OS in human GCs, and this could provide novel insight to conquer the age-related fertility decline that is mainly attributed to the accumulation of aberrant OS.

Administration of Oral Contraceptives Could Alleviate Age-Related Fertility Decline Possibly by Preventing Ovarian Damage in a Mouse Model.

Age-related fertility decline is hypothesized to occur mainly by the spontaneous exhaustion and deterioration of the ovarian follicle, and the accumulation of ovarian tissue damage resulting from the ovulation cycle may play roles in the process. In this study, we hypothesized that suppressing ovulation would exert protective effects against age-related fertility decline. To test this hypothesis, we established a mouse model in which oral contraceptives (OCs) were administered daily. Female C57BL/6N mice were administered OCs daily from the age of 2 months to 12 months as an ovulation suppression mouse model. Mouse fecundity was investigated by counting oocyte number after ovarian stimulation and by examining live fetuses after mating. We found that compared with control mice administered vehicle alone, 12-month-old mice administered 2-fold dose OCs used for treating humans exhibited a significantly greater average oocyte number after ovarian stimulation (8.5 ± 0.6 vs 5.9 ± 0.6, P < .01). In addition, spontaneous conception with living fetuses after mating was strikingly increased in 12-month-old mice administered OCs relative to controls (6.0 ± 1.2 vs 0.4 ± 0.3, P < .01). In the histological examination of mouse ovarian tissues, we did not detect a significant difference in ovarian follicle number, but reduced amount of brownish foamy fibrous tissues, which might reflect ovarian tissue damage, was detected in aged mice administered OCs. These results suggest the possibility that long-term OC administration might alleviate age-related fertility decline, and the improvement mechanism could be attributed to the prevention of ovarian tissue damage by suppressing ovulation.