Is neonatal uterine bleeding responsible for early-onset endometriosis?

BACKGROUND: It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis. METHODS: We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB. RESULTS: Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria. CONCLUSIONS: Based on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance. TRIAL REGISTRATION: not applicable.

A targeted educational programme improves fundamental knowledge of menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project.

RESEARCH QUESTION: Would a properly designed educational programme offered to young women improve their awareness and fundamental knowledge of menstrual pain and endometriosis? DESIGN: A multinational cross-sectional study using a pen-and-paper questionnaire among women aged 19-24 years was conducted between 2017 and 2019 to assess fundamental knowledge of menstrual pain and endometriosis. Improvement in knowledge was also analysed using a separate questionnaire completed before, and 1-3 months after, a group discussion, lecture on menstrual pain and endometriosis, or both. RESULTS: Among three groups of students (college [n = 271], medical [n = 877] and nursing [n = 763]), knowledge of menstrual pain and endometriosis was lowest among college students, modest among nursing students and fair among medical students (P < 0.001 for each). The experience of cyclical pain, even when painkillers were taken, was reported by 15.5%, 4.6% and 3.8% of students, respectively. Most students managed their cyclical pain by enduring it or by taking over-the-counter medication. An informative education programme with group discussions, lectures, or both, was successful in improving knowledge and consequences of menstrual pain and endometriosis. Proper education and dissemination of knowledge to college students failed to motivate them to visit gynaecologists; however, medical and nursing students became highly interested in visiting gynaecologists. CONCLUSIONS: An educational programme can improve awareness and knowledge of endometriosis and dysmenorrhoea among young women. The programme motivated nursing and medical students, but not college students, to seek medical attention for early detection and management of endometriosis.

Bleeding patterns of women with heavy menstrual bleeding or dysmenorrhoea using the levonorgestrel-releasing intrauterine system: results from a real-world observational study in Japan (J-MIRAI).

PURPOSE: To collect real-world safety and clinical outcome data on the levonorgestrel-releasing intrauterine system (LNG-IUS) for functional/organic heavy menstrual bleeding (HMB) and dysmenorrhoea in Japanese women (J-MIRAI). MATERIALS AND METHODS: In this prospective, multicentre, single-cohort, open-label, post-authorisation study, we assessed menstrual blood loss after LNG-IUS insertion by changes from baseline in pictorial blood loss assessment chart (PBAC) scores. Scores for the menorrhagia multi-attribute scale (MMAS) were collected for 12 months to assess quality of life. RESULTS: We included 47 patients with complete PBAC score and patient diary data. The median PBAC score before LNG-IUS insertion was 159.0, which decreased significantly to 6.0 at 12 months post-insertion; for patients with adenomyosis (n = 20), PBAC score decreased from 174.5 pre-insertion to 19.5 at 12 months. The number of patient-reported bleeding days was correlated with PBAC score ≥5. The proportion of women with prolonged bleeding decreased from 85.7% to 34.6% by the study's end. Some women reported no bleeding after the first 90-day reference period. The mean MMAS overall score significantly increased from 50.50 before insertion to 88.67 at 12 months. CONCLUSIONS: Japanese women with functional/organic HMB experienced substantial reductions in bleeding symptoms and improvements in quality of life after 12-month use of the LNG-IUS.

Occurrence of chronic endometritis in different types of human adenomyosis.

Purpose: Human adenomyosis has an adverse effect on female fertility. Exact mechanistic basis is still unclear. We investigated the occurrence of chronic endometritis (CE) in different types of human adenomyosis. Methods: This is a prospective non-randomized observational study enrolling patients with focal (n = 30), diffuse (n = 26), intrinsic (n = 23), and extrinsic (n = 10) adenomyosis. Endometrial biopsy samples were collected from hysterectomy specimens. Immunohistochemical analysis was performed using antibody against CD68 (Mφ marker) with biopsy samples of intrinsic/extrinsic adenomyosis and CD138 (Syndecan-1), a marker of plasma cells, in all biopsy samples. Results: In GnRHa-untreated groups, a higher trend in the occurrence of CE, as characterized by infiltration of ≥1 plasma cells in endometrial stroma, was found in women with focal (58.8%, p = 0.0849) and diffuse adenomyosis (60.0%, p = 0.0841) comparing to control women (10.0%). In women with focal adenomyosis, ipsilateral side showed a significantly higher occurrence of CE (58.8%) than on the contralateral side (11.7%) (p = 0.043). Tissue infiltration of macrophages in endometria was significantly higher in intrinsic than in extrinsic adenomyosis (p = 0.03) without showing any significant difference in the occurrence of CE between these two variants of adenomyosis. Conclusion: A variable occurrence of CE in different types of adenomyosis may be involved in adverse reproductive outcome.

An axonemal alteration in apical endometria of human adenomyosis.

STUDY QUESTION: Is there any change in the distribution of microvilli and microtubules in the apical endometria of women with adenomyosis? SUMMARY ANSWER: We observed microvilli damage in the apical endometria and an axonemal alteration characterized by abnormal distribution of longitudinal bundles of microtubules within microvilli in women with adenomyosis. WHAT IS KNOWN ALREADY: Human adenomyosis has a negative impact on female fertility. Abnormal utero-tubal sperm transport, tissue inflammation and toxic effect of chemical mediators have been proposed as contributing factors. Inflammation-induced damage of mucosal cilia in the Fallopian tube has been reported. However, information on inflammation-induced damage of microvilli on the apical endometrial cells and its core bundles of microtubules in adenomyosis remains unknown. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study with subjects undergoing laparoscopic surgery or hysterectomy for clinical indication and evaluations of endometrial biopsy samples in two academic university hospitals. During the period between March 2015 and December 2018, endometrial biopsy samples were prospectively collected from 15 control women and 45 women with adenomyosis for immunohistochemical analysis and a separate cohort of 10 control women with cervical intraepithelial neoplasia Grade 3 (CIN3) and 20 women with adenomyosis for analysis by immunohistochemistry and transmission electron microscopy (TEM). PARTICIPANTS/MATERIALS, SETTING, METHODS: For immunohistochemical study, endometrial biopsy samples were prospectively collected from 15 control women with fibroids, 25 women with focal adenomyosis and 20 women with diffuse adenomyosis after surgery. The diagnosis of fibroid and adenomyosis was made clinically by transvaginal ultrasonography and magnetic resonance imaging and confirmed by histology. Immunohistochemical analysis was performed retrospectively using antibody against CD68 (marker of macrophages) in endometrial biopsy specimens of women with and without adenomyosis. TEM was performed with the apical endometria collected from a separate cohort of 10 control women with CIN3 and 20 women with focal and diffuse adenomyosis for the identification of any change in the distribution of microvilli and longitudinal bundles of microtubules within microvilli. MAIN RESULTS AND ROLE OF CHANCE: Comparing to control endometria and contralateral side, tissue infiltration of macrophages (Mφ) in the endometria was significantly higher on the ipsilateral side of focal adenomyosis (P = 0.02 and P = 0.03, respectively) and anterior/posterior walls of diffuse adenomyosis (P = 0.01 for both). In a subgroup analysis of patients with focal adenomyosis with and without symptoms, the endometria of symptomatic women displayed a tendency of higher Mφ infiltration on the ipsilateral side than in asymptomatic women (P = 0.07). Comparing to contralateral side endometria of symptomatic women, Mφ infiltration was significantly higher in the endometria of symptomatic women collected from the ipsilateral side of focal adenomyosis (P = 0.03). We found a significantly less tissue infiltration of Mφ in the endometria of women with CIN3 than that in endometria of women with focal adenomyosis. TEM analysis showed that number of microvilli in the endometria was significantly decreased on the ipsilateral side (P = 0.003) comparing to that on the contralateral side of focal adenomyosis. The Chi-squared test indicated that cases with abnormal (disruption in the normal arrangement of 9 peripheral pairs + 1 central pair) microtubules (MT) were significantly higher in women with adenomyosis than in cases with normal patterns (P = 0.0016). While contralateral side displayed significantly less abnormal MT (P = 0.0002), ipsilateral side of focal adenomyosis showed significantly higher abnormal MT (P = 0.0164) comparing to normal patterns. Cases with symptomatic adenomyosis showed significantly higher abnormal MT than normal MT (P = 0.0004). An axonemal alteration characterized by abnormal structural distribution of microtubules within microvilli in the apical endometria in response to endometrial inflammation may be involved in adverse reproductive outcome in women with adenomyosis. LIMITATIONS, REASONS FOR CAUTION: The average age of women in this study was high that may be associated with overall decline in fertility regardless of the presence or absence of adenomyosis or endometriosis. We collected endometrial biopsy samples from two completely separate cohorts of women for analysis by immunohiostochemistry and TEM. We need future follow-up study with increased sample size and from the same patients to precisely clarify the mechanistic link between axonemal alteration and negative fertility outcome. WIDER IMPLICATIONS OF THE FINDINGS: Our current findings may have some biological implication to better understand the endometrial epithelial biology and pathology in women with adenomyosis and may open the avenue for future study in other reproductive diseases. The ultra-structural abnormalities of microvilli and microtubules in the apical endometria in response to tissue inflammatory reaction may clarify the possible association between negative fertility outcome and adenomyosis. Our findings may be clinically useful during counseling with symptomatic patients with adenomyosis desiring pregnancy. STUDY FUNDING/COMPETING INTEREST (S): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: N/A.

Epitranscriptomic profiling in human placenta: N6-methyladenosine modification at the 5'-untranslated region is related to fetal growth and preeclampsia.

Intracellular mRNA levels are not always proportional to their respective protein levels, especially in the placenta. This discrepancy may be attributed to various factors including post-transcriptional regulation, such as mRNA methylation (N6-methyladenosine: m6A). Here, we conducted a comprehensive m6A analysis of human placental tissue from neonates with various birth weights to clarify the involvement of m6A in placental biology. The augmented m6A levels at the 5'-untranslated region (UTR) in mRNAs of small-for-date placenta samples were dominant compared to reduction of m6A levels, whereas a decrease in m6A in the vicinity of stop codons was common in heavy-for-date placenta samples. Notably, most of these genes showed similar expression levels between the different birth weight categories. In particular, preeclampsia placenta samples showed consistently upregulated SMPD1 protein levels and increased m6A at 5'-UTR but did not show increased mRNA levels. Mutagenesis of adenosines at 5'-UTR of SMPD1 mRNAs actually decreased protein levels in luciferase assay. Collectively, our findings suggest that m6A both at the 5'-UTR and in the vicinity of stop codon in placental mRNA may play important roles in fetal growth and disease.

Successful management of acquired hemophilia A onset during pregnancy: A case report.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII. Pregnancy could be associated with AHA in younger women. Because of its rarity, the optimal management for pregnancy-related AHA has not yet been established. Herein, we present the case of a 32-year-old woman with AHA diagnosed during pregnancy because of elevated activated partial prothrombin time, decreased factor VIII activity, and the presence of a factor VIII inhibitor. She was treated with immunosuppressive therapy consisting of corticosteroid and cyclosporine administration. Although complete remission could not be induced in the peripartum period, she gave birth safely by cesarean delivery in combination with prophylactic bypass hemostatic therapy. This work would provide helpful information to guide better recognition and treatment of pregnancy-related AHA cases.

Severe coronavirus disease pneumonia in a pregnant woman at 25 weeks' gestation: A case report.

There are numerous reports on the effects of the coronavirus disease on mothers and fetuses during pregnancy. It is currently unknown whether pregnancy is associated with a high risk of severe coronavirus disease. We report a pregnant patient with coronavirus disease who underwent a cesarean section. A pregnant 39-year-old Japanese woman was diagnosed with coronavirus disease at 25 weeks of gestation. Her breathing condition worsened daily, and she required oxygen administration. On day 6 of her 26th week of gestation, she developed severe pneumonia and required tracheal intubation and artificial ventilation, and an emergency cesarean section was performed under general anesthesia. It is necessary to investigate the risk of increased coronavirus disease severity during pregnancy, the effects of coronavirus disease on perinatal prognosis, and the management of pregnancy with coronavirus disease.

Successful detection of rectal injury during laparoscopic surgery using a rectal probe in a patient with deep endometriosis.

Laparoscopic surgery has become the gold standard treatment for endometriosis. Surgical treatment of deep endometriosis with colorectal involvement is challenging. It requires complete surgical excision of lesions despite a high risk of complications that include rectal injury, rectovaginal fistula and pelvic abscess. An intraoperative air leak test allows detection of rectal injury and reduces postoperative complications. We report a case of successful management of rectal injury during laparoscopic surgery using a rectal probe even though air leak tests were negative. A 45-year-old woman with severe endometriosis and rectal involvement underwent total laparoscopic hysterectomy combined with rectal shaving. A pinhole injury that reached the rectal muscularis layer without breaching the mucosal layer was identified using a rectal probe after negative air leak tests. The injury was repaired uneventfully. Our experience suggests that using a rectal probe could be helpful for early detection and safe repair of rectal injury during surgery.

Benign metastasizing leiomyoma in femur and thigh with a history of uterine leiomyoma: A case report and literature review.

Benign metastasizing leiomyoma (BML) is a rare disease that is characterized by well-differentiated smooth muscle tumors occurring extrauterine site in women with a history of uterine leiomyoma. The lung is the most common metastatic site for BML. A 48-year-old woman, who had histories of laparoscopic myomectomy and transabdominal total hysterectomy, visited an orthopedics complaining of a mass in her left thigh and difficulty in walking. Magnetic resonance imaging (MRI) and fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple mass lesions in her both thighs and left femur as well as both lungs. She was referred to our hospital for further examination. We diagnosed her tumors as BML according to histopathological analysis of tumor specimen. The left thigh tumor was resected and the treatment with gonadotropin releasing hormone agonist regressed the size of the residual tumors by approximately 30%. BML should be considered when multiple soft tissue tumors are found in women with a history of leiomyomas.

National survey of bladder endometriosis cases in Japan.

AIM: We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE). METHODS: We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence. RESULTS: Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p < 0.05). The recurrence rate tended to be higher after laparoscopic PC (n = 24) than after open PC (n = 20), but the difference was not statistically significant (p = 0.0879). Of the nine nonsurgical patients, eight received hormonal therapy and one did not. Efficacy rates of dienogest, GnRH agonist, and OC were 85.7%, 66.7%, and 66.7%, respectively. Of five patients with BE extending to the ureter or ureteral orifices, two underwent PC and ureteroneocystostomy and one underwent total nephroureterectomy due to renal function loss. CONCLUSION: To our knowledge, this is the first study to compare the postoperative recurrence of BE after TUR and PC. We found that cumulative recurrence rate is significantly lower after PC than after TUR. BE extending to the ureter or ureteral orifices is a very challenging condition. Further studies are required for the optimal management of BE.

An assessment of the efficacy and safety of dydrogesterone in women with ovarian endometrioma: An open-label multicenter clinical study.

PURPOSE: To assess the efficacy and safety of dydrogesterone in Japanese women with ovarian endometrioma in a real-world setting. METHODS: The post-marketing study involved 15 sites in Japan. Dydrogesterone 10 mg twice daily orally was administered for 21 days (day 5-25 of each menstrual cycle) for 4 cycles. The primary outcome measure was the change in ovarian endometrioma volume from baseline. Secondary outcome measures included total dysmenorrhea score (0 = absent to 3 = severe), severity of dysmenorrhea pain [0-10cm visual analog scale (VAS)], serum carbohydrate antigen 125 (CA-125) levels, and safety. RESULTS: The study group comprised women with an endometrioma aged 20 to 49 (47.4% cases aged ≥40 years). Endometrioma volume was reduced in 50% (26/52), unchanged in 25% (13/52), and increased in 25% (13/52) of women from baseline to the end of cycle 5; three-quarters of patients thus had either reduced or unchanged ovarian endometrioma volume. Dydrogesterone significantly reduced total dysmenorrhea scores and severity of dysmenorrhea pain VAS during treatment compared with baseline. CA-125 levels were not significantly changed during the study. The incidence of adverse events and adverse drug reactions in 59 subjects was 13.6% and 11.9%. CONCLUSIONS: Dydrogesterone prevented an increase in endometrioma size in many women, and it also significantly improved total dysmenorrhea scores and severity of dysmenorrhea pain, and was well tolerated. The ClinicalTrials.gov identifier of the study was NCT02921763.

Effectiveness and Tolerability of Oral Amoxicillin in Pregnant Women with Active Syphilis, Japan, 2010-2018.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010-2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

Synergistic effect of the inhibitors of RAF/MEK and AXL on KRAS-mutated ovarian cancer cells with high AXL expression.

KRAS mutation is frequently seen in a subtype of ovarian cancer categorized as type 1. The KRAS-MAPK pathway, which is closely involved in type 1 cancer progression, is under the regulation of receptor tyrosine kinases (RTKs). AXL, one of the RTKs, has been reported to be overexpressed in ovarian cancer and contributes to the poor prognosis. However, there is no useful target-based agent against such gene profiles. We examined the combined effect of the dual RAF/MEK inhibitor CH5126766 and AXL inhibitor R428 on the growth of ovarian cancer HEY-T30 and OVCAR-5 cell lines, both of which bear KRAS mutation and express AXL at a high level, using the WST-8 assay and the colony formation assay. The synergistic effect of the combination was evaluated by the combination index. The apoptotic cells were analyzed by flow cytometry. The expression of apoptotic proteins and the phosphorylation of MAPK and AKT pathway proteins were investigated by western blotting. We found that CH5126766 and R428 suppressed the phosphorylation of ERK and AKT, respectively, and their combination synergistically inhibited the growth of both cell lines with enhancement of apoptosis accompanied by the Bim upregulation. Combined treatment with CH5126766 and R428 is expected as the novel therapeutic option for KRAS-mutated ovarian cancer with high expression of AXL.

A National Survey of Umbilical Endometriosis in Japan.

STUDY OBJECTIVE: To identify the clinical presentation, diagnostic evaluation, operative or medical management, and postoperative recurrence of umbilical endometriosis. DESIGN: A retrospective national survey. SETTING: Obstetrics and Gynecology and Plastic Surgery Departments at a teaching hospital in Japan. PATIENTS: Patients with umbilical endometriosis or malignant transformation. INTERVENTIONS: A national survey was conducted to identify and evaluate cases of umbilical endometriosis or malignant transformation documented between 2006 and 2016. MEASUREMENTS AND MAIN RESULTS: The following were evaluated for each patient: age at diagnosis, body mass index, medical history, presence of extragenital endometriosis, surgical history, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence, and time to recurrence. Ninety-six patients were identified with pathologically diagnosed benign umbilical endometriosis. The patients frequently had swelling (86.5%), pain (81.3%), or bleeding (44.8%) in the umbilicus. Sensitivity was 87.1% for physical examination, 76.5% for transabdominal ultrasonography, 75.6% for computed tomography, and 81.8% for magnetic resonance imaging. The cumulative recurrence rate was 1.34% at 6 months, 6.35% at 12 months, and 6.35% at 60 months after surgery. Importantly, there was no recurrence after wide resection including of the peritoneum (0 of 37 cases). The efficacy of dienogest (an oral progestin), gonadotropin-releasing hormone agonists, and oral contraceptives was 91.7%, 81.8%, and 57.1%, respectively. Finally, 2 cases of malignant transformation were identified. CONCLUSION: There was a low recurrence rate following surgery, and hormonal treatment is an option, although the current findings suggest surgical therapy as the first choice of treatment for umbilical endometriosis.

Prenatal diagnosis of fetal skeletal dysplasia using 3-dimensional computed tomography: a prospective study.

BACKGROUND: Fetal skeletal dysplasia (FSD) comprises a complex group of systemic bone and cartilage disorders. Many FSD phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. The condition is typically diagnosed using sonography; however, three-dimensional computed tomography (3D-CT) also aids in making a prenatal diagnosis. This study aimed to examine the efficacy of 3D-CT in the prenatal diagnosis of FSD by comparing the diagnostic accuracy of fetal sonography and 3D-CT. METHODS: On suspicion of FSD based on ultrasound examination, we performed 3D-CT prenatally to obtain detailed skeletal information on FSD. To minimize exposure of the fetuses to radiation without compromising image quality, we used predetermined 3D-CT settings for volume acquisition. RESULTS: Nineteen fetuses were suspected of having skeletal dysplasia based on ultrasonography findings. Of these, 17 were diagnosed with FSD using 3D-CT. All 17 fetuses diagnosed with FSD prenatally were confirmed postnatally to have the condition. The postnatal diagnosis (campomelic dysplasia) differed from the prenatal diagnosis (osteogenesis imperfecta) in only one infant. Sixteen cases (94.1%) were diagnosed both prenatally and postnatally with FSD. Five infants had lethal skeletal dysplasia; one died in utero, and four died as neonates. We determined the appropriate delivery method for each infant based on the prenatal diagnosis. CONCLUSIONS: 3D-CT is a valuable tool for augmenting ultrasound examinations in the diagnosis of FSD. While improving the diagnostic tool of sonography is essential in cases of suspected FSD, 3D-CT imaging is indispensable for diagnosis and classification, enabling better planning for resuscitation of the infant after birth. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Center trial registration number is UMIN000034744 . Registered 1 October, 2018 - Retrospectively registered.

Validity of stress assessment using heart-rate variability in newborns.

BACKGROUND: The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level. METHODS: We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined. RESULTS: The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time. CONCLUSIONS: The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.

Annual report of the Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2019.

Since 2010, the Women's Health Care Committee has continuously addressed issues closely linked to women's quality of life. The five agendas this committee has engaged for this academic year are as follows: (i) clinical study of urinary complications in perinatal and post-partum women's health care; (ii) enlightenment of infectious diseases in Obstetrics and Gynecology in Japan; (iii) educational activities regarding management guidelines for health care in female athletes; (iv) training program for women's health-care advisers; and (v) pregnancy- and lactation-associated osteoporosis (PLOP). The detailed activities of the five subcommittees are described herein. This report is based on the Japanese version of our annual report (Acta Obst Gynaec Jpn 2019;71(6): 889-898), which publicizes the activities of our committee.

Unexpected tumor-to-tumor metastasis of synovial sarcoma within leiomyoma: A case report and literature review.

A tumor metastasis within another tumor is known as tumor-to-tumor metastasis (TTM). We report a 43-year-old woman who presented with hypermenorrhea and an abdominal mass. She had history of a soft tissue tumor on her left ankle at 38 years of age. Laboratory data showed slight elevation of CA125 and no other abnormal findings and magnetic resonance imaging revealed a circumscribed margin mass in the uterine fundus. We diagnosed the mass as benign leiomyoma and performed total laparoscopic hysterectomy. Postoperative pathological examination revealed TTM of synovial sarcoma within the uterine leiomyoma. A database search identified 29 cases of TTM within uterine leiomyoma. The donor tumor was mostly breast cancer (in 23 cases). To the best of our knowledge, this is the first report of a sarcoma TTM to a uterine leiomyoma. Despite the difficulty of preoperative diagnosis, TTM should be considered during the treatment approach for a patient with leiomyoma and a history of malignant tumors.

Clinical practice guidelines for the treatment of extragenital endometriosis in Japan, 2018.

The aim of this publication is to disseminate the clinical practice guidelines for the treatment of intestinal, bladder/ureteral, thoracic and umbilical endometriosis, already published in Japanese, to non-Japanese speakers. For developing the original Japanese guidelines, the clinical practice guideline committee was formed by the research team for extragenital endometriosis, which is part of the research program of intractable disease of the Japanese Ministry of Health, Labor and Welfare. The clinical practice guideline committee formulated eight clinical questions for the treatment of extragenital endometriosis, which were intestinal, bladder/ureteral, thoracic and umbilical endometriosis. The committee performed a systematic review of the literature to provide responses to clinical questions and developed clinical guidelines for extragenital endometriosis, according to the process proposed by the Medical Information Network Distribution Service. The recommendation level was determined using modified Delphi methods. The clinical practice guidelines were officially approved by the Japan Society of Obstetrics and Gynecology and the Japan Society of Endometriosis. This English version was translated from the Japanese version.