Rapamycin prevents cyclophosphamide-induced ovarian follicular loss and potentially inhibits tumour proliferation in a breast cancer xenograft mouse model.

STUDY QUESTION: To what extent and via what mechanism does the concomitant administration of rapamycin (a follicle activation pathway inhibitor and antitumour agent) and cyclophosphamide (a highly toxic ovarian anticancer agent) prevent cyclophosphamide-induced ovarian reserve loss and inhibit tumour proliferation in a breast cancer xenograft mouse model? SUMMARY ANSWER: Daily concomitant administration of rapamycin and a cyclic regimen of cyclophosphamide, which has sufficient antitumour effects as a single agent, suppressed cyclophosphamide-induced primordial follicle loss by inhibiting primordial follicle activation in a breast cancer xenograft mouse model, suggesting the potential of an additive inhibitory effect against tumour proliferation. WHAT IS KNOWN ALREADY: Cyclophosphamide stimulates primordial follicles by activating the mammalian target of the rapamycin (mTOR) pathway, resulting in the accumulation of primary follicles, most of which undergo apoptosis. Rapamycin, an mTOR inhibitor, regulates primordial follicle activation and exhibits potential inhibitory effects against breast cancer cell proliferation. STUDY DESIGN, SIZE, DURATION: To assess ovarian follicular apoptosis, 3 weeks after administering breast cancer cells, 8-week-old mice were randomized into three treatment groups: control, cyclophosphamide, and cyclophosphamide + rapamycin (Cy + Rap) (n = 5 or 6 mice/group). Mice were treated with rapamycin or vehicle control for 1 week, followed by a single dose of cyclophosphamide or vehicle control. Subsequently, the ovaries were resected 24 h after cyclophosphamide administration (short-term treatment groups). To evaluate follicle abundance and the mTOR pathway in ovaries, as well as the antitumour effects and impact on the mTOR pathway in tumours, 8-week-old xenograft breast cancer transplanted mice were randomized into three treatment groups: vehicle control, Cy, and Cy + Rap (n = 6 or 7 mice/group). Rapamycin (5 mg/kg) or the vehicle was administered daily for 29 days. Cyclophosphamide (120 mg/kg) or the vehicle was administered thrice weekly (long-term treatment groups). The tumour diameter was measured weekly. Seven days after the last cyclophosphamide treatment, the ovaries were harvested, fixed, and sectioned (for follicle counting) or frozen (for further analysis). Similarly, the tumours were resected and fixed or frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS: Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was performed to examine ovarian follicular apoptosis in the short-term treatment groups. All subsequent experiments were conducted in the long-term treatment groups. Tumour growth was evaluated using the tumour volume index. The tumour volume index indicates the relative volume, compared to the volume 3 weeks after tumour cell injection (at treatment initiation) set to 100%. Tumour cell proliferation was evaluated by Ki-67 immunostaining. Activation of the mTOR pathway in tumours was assessed using the protein extracts from tumours and analysed by western blotting. Haematoxylin and eosin staining of ovaries was used to perform differential follicle counts for primordial, primary, secondary, antral, and atretic follicles. Activation of the mTOR pathway in ovaries was assessed using protein extracts from whole ovaries and analysed by western blotting. Localization of mTOR pathway activation within ovaries was assessed by performing anti-phospho-S6 kinase (downstream of mTOR pathway) immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: Ovaries of the short-term treatment groups were resected 24 h after cyclophosphamide administration and subjected to TUNEL staining of apoptotic cells. No TUNEL-positive primordial follicles were detected in the control, Cy, and Cy + Rap groups. Conversely, many granulosa cells of growing follicles were TUNEL positive in the Cy group but negative in the control and Cy + Rap groups. All subsequent experimental results were obtained from the long-term treatment groups. The tumour volume index stabilized at a mean of 160-200% in the Cy group and 130% in the Cy + Rap group throughout the treatment period. In contrast, tumours in the vehicle control group grew continuously with a mean tumour volume index of 600%, significantly greater than that of the two treatment groups. Based on the western blot analysis of tumours, the mTOR pathway was activated in the vehicle control group and downregulated in the Cy + Rap group when compared with the control and Cy groups. Ki-67 immunostaining of tumours showed significant inhibition of cell proliferation in the Cy + Rap group when compared with that in the control and Cy groups. The ovarian follicle count revealed that the Cy group had significantly fewer primordial follicles (P < 0.001) than the control group, whereas the Cy + Rap group had significantly higher number of primordial follicles (P < 0.001, 2.5 times) than the Cy group. The ratio of primary to primordial follicles was twice as high in the Cy group than in the control group; however, no significant difference was observed between the control group and the Cy + Rap group. Western blot analysis of ovaries revealed that the mTOR pathway was activated by cyclophosphamide and inhibited by rapamycin. The phospho-S6 kinase (pS6K)-positive primordial follicle rate was 2.7 times higher in the Cy group than in the control group. However, this effect was suppressed to a level similar to the control group in the Cy + Rap group. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: The combinatorial treatment of breast cancer tumours with rapamycin and cyclophosphamide elicited inhibitory effects on cell proliferative potential compared to cyclophosphamide monotherapy. However, no statistically significant additive effect was observed on tumour volume. Thus, the beneficial antitumour effect afforded by rapamycin administration on breast cancer could not be definitively proven. Although rapamycin has ovarian-protective effects, it does not fully counteract the ovarian toxicity of cyclophosphamide. Nevertheless, rapamycin is advantageous as an ovarian protective agent as it can be used in combination with other ovarian protective agents, such as hormonal therapy. Hence, in combination with other agents, mTOR inhibitors may be sufficiently ovario-protective against high-dose and cyclic cyclophosphamide regimens. WIDER IMPLICATIONS OF THE FINDINGS: Compared with a cyclic cyclophosphamide regimen that replicates human clinical practice under breast cancer-bearing conditions, the combination with rapamycin mitigates the ovarian follicle loss of cyclophosphamide without interfering with the anticipated antitumour effects. Hence, rapamycin may represent a new non-invasive treatment option for cyclophosphamide-induced ovarian dysfunction in breast cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This work was not financially supported. The authors declare that they have no conflict of interest.

Pregnancy and lactation-associated osteoporosis as a major type of premenopausal osteoporosis: a retrospective cohort study based on real-world data.

BACKGROUND: Pregnancy and lactation-associated osteoporosis (PLO), as well as premenopausal osteoporosis, might be a predictor of future fracture. This study aimed to describe the clinical features of PLO as a subtype of premenopausal osteoporosis and to evaluate medical interventions for it. METHODS: From an administrative claims database including 4,224,246 people in Japan, we classified women for whom the date of childbirth had been defined and who had suffered low-trauma fracture between the ages of 18-47 years as the premenopausal osteoporosis group. A fracture site for which the odds ratio for fractures occurring between 5 months before and 12 months after childbirth (around childbirth) was greater than 1 was considered the PLO site. We classified patients with a fracture at the PLO site around childbirth as the PLO group. The control group consisted of 500 women without fragility fractures. We investigated some drugs and diseases to explore fracture-causing factors, as well as medical interventions such as osteoporosis diagnosis, bone densitometry, anti-osteoporosis pharmacotherapy, and lactation inhibitors. RESULTS: In total, 231 parous women were classified into the premenopausal osteoporosis group. The most common fracture was vertebral fracture and was likely to occur around childbirth, followed by distal radius and sacral fractures, which were rare around childbirth. Considering vertebral, pelvic, and proximal femoral fractures as PLO sites, 56 women with 57 PLO fractures were classified into the PLO group. The incidence of PLO was estimated at 460 per million deliveries. Ovulation disorder and high maternal age were associated with the development of PLO. Vertebral fracture was the most common PLO fracture. It was mainly diagnosed a few months, and possibly up to 1 year, postpartum. PLO patients with vertebral fractures underwent more medical interventions than did those with other fractures, but they were still inadequate. CONCLUSIONS: PLO with vertebral fracture was one of the major types of premenopausal osteoporosis. The prevalence of PLO is considered to be higher than previously thought, indicating the presence of potentially overlooked patients. More timely interventions for PLO might lead to the improved management of latent patients with premenopausal osteoporosis and reduce future fracture risk.

Clinical outcomes and future fertility after uterine artery embolization for postpartum and post-abortion hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) and post-abortion hemorrhage (PAH) are life-threatening conditions. PURPOSE: To evaluate the efficacy and safety of uterine arterial embolization (UAE) for PPH and PAH and to investigate future fertility after UAE. MATERIAL AND METHODS: This study included 57 consecutive patients (mean age = 34 years) who underwent UAE for PPH (n = 46) and PAH (n = 11) at our institution between January 2011 and December 2022. Technical success, non-visualization of the peripheral portion of bilateral uterine arteries on angiography, and clinical success, complete hemostasis after UAE, were assessed. UAE-associated complications and factors related to clinical success were analyzed. Pregnancy outcomes after UAE and complications during subsequent pregnancy were investigated in 16 patients who desired fertility and were followed up for >1 year. RESULTS: The technical and clinical success rates were 100% and 84.2%, respectively. Sepsis (n = 1) and uterine empyema (n = 1) were observed as severe complications. Placental disorder, bleeding within 24 h after delivery or abortion, ≥1.5 shock index, ≥6 units of transfusion erythrocytes, and ≥8 obstetrical disseminated intravascular coagulation score were significantly associated with unfavorable clinical outcomes. In total, 16 pregnancies were observed in 12 patients after UAE, three of which were miscarriages and 13 were successful live births. During pregnancy, uterine rupture (n = 1) and accreta (n = 1) were observed. CONCLUSION: UAE is an effective treatment for PPH and PAH. Although UAE could preserve future fertility, careful attention should be paid to perinatal management for unusual complications.

Successful perinatal management of a woman with congenital factor XIII deficiency using recombinant factor XIII: A case report and literature review.

Factor XIII deficiency is an extremely rare autosomal recessive genetic disorder, occurring in 1 of 3-5 million people, and is associated with perinatal complications, such as habitual abortion and prolonged bleeding. Although plasma-derived factor XIII (Fibrogamin®) carries a risk of infection and contains very low concentrated forms of factor XIII (FXIII) used for a pregnant woman with congenital coagulation factor XIII deficiency, recombinant factor XIII (rFXIII, Novo Thirteen®; Tretten®, Novo Nordisk, Bagsvaerd, Denmark), which has no risk of infection and is highly concentrated, has emerged as a novel formulation. Herein, we report the first case of a Japanese pregnant woman with congenital coagulation factor XIII deficiency successfully managed by rFXIII. She had a good perinatal course without pregnancy-related complications and transfusion through the perinatal period.

Effectiveness of an articulating laparoscopic needle holder for cesarean scar defect repair.

AIM: To evaluate the efficacy of an articulating laparoscopic needle holder in laparoscopic surgery for cesarean scar defect. METHODS: We performed a retrospective case-control study at the Shiga University of Medical Science. Patients who underwent laparoscopic uterine scar repair were divided into an articulating laparoscopic needle holder (ArtiSential®) group and a rigid needle holder (conventional) group to compare the suture and total operative times. Uterine myometrial suturing involves a double-layer interrupted suture, including a modified Gambee suture for the first layer. We measured the residual myometrial thickness using magnetic resonance imaging preoperatively and at 3 months postoperatively. RESULTS: Both groups comprised 10 patients each. The time per stitch for the first and second layers was significantly shorter in the ArtiSential group than in the conventional group (median 208 s vs. 403 s, p < 0.0001 and median 17 s vs. 29 s; p < 0.0001, respectively). The total operating time was significantly shorter in the ArtiSential group (mean 188 min vs. 240 min, p = 0.0015). The postoperative residual myometrial thickness (mean 9.1 mm in the ArtiSential group and 9.6 mm in the conventional group) was significantly higher than the preoperative residual myometrial thickness (mean 1.6 mm in the ArtiSential group and 1.6 mm in the conventional group) (p < 0.0001 in both groups). CONCLUSIONS: An articulating needle holder is useful in laparoscopic surgery for cesarean scar defect, especially when a modified Gambee suture is required.

Cases of pleural effusion possibly due to clinical pleuroperitoneal communication in the perioperative period of emergency gynecologic surgery: Case series and literature review.

Pleuroperitoneal communication poses a respiratory failure risk due to pleural fluid accumulation with thoracic migration of ascites. Here, we discuss the following cases: Case 1: A woman was diagnosed with a ruptured ovarian tumor with right pleural fluid and ascites, without respiratory failure. Ovarian cystectomy was performed with inadequate removal of ascites. Postoperatively, respiratory failure occurred, and thoracentesis detected pleural fluid resembling ascites. Case 2: A woman was diagnosed with a ruptured ectopic pregnancy with right pleural fluid and ascites without respiratory failure. A diagnosis of clinical pleuroperitoneal communication was considered based on computed tomography findings. During laparoscopic salpingectomy, high-pressure ventilation was performed to push the pleural fluid back into the abdominal cavity; a negative-pressure drain was inserted, and the ascites was completely removed. Postoperative radiography revealed the absence of pleural fluid. Therefore, a preoperative diagnosis of clinical pleuroperitoneal communication and appropriate intraoperative techniques can prevent postoperative respiratory failure.

Indication Criteria of Hysteroscopic Surgery for Secondary Infertility due to Symptomatic Cesarean Scar Defect Based on Clinical Outcomes: A Retrospective Cohort Study.

STUDY OBJECTIVE: Hysteroscopic surgery criteria for patients with cesarean scar defect (CSD) are unclear. Therefore, this study aimed to explore the indication of hysteroscopic surgery for secondary infertility owing to CSD. DESIGN: Retrospective cohort study. SETTING: Single university hospital. PATIENTS: Seventy patients with secondary infertility owing to symptomatic CSD who underwent hysteroscopic surgery under laparoscopy between July 2014 and February 2022 were included. INTERVENTIONS: Clinical data, including basic patient information, preoperative residual myometrial thickness (RMT), and postoperative pregnancy status, were collected from medical records. Patients were divided into postoperative pregnancy and nonpregnancy groups. A receiver operating characteristic curve was drawn, and the optimal cutoff value was calculated based on the area under the curve to predict pregnancy after hysteroscopic surgery. MEASUREMENTS AND MAIN RESULTS: No complications were observed in any cases. Among the 70 patients, 49 patients (70%) became pregnant after hysteroscopic surgery. There was no significant difference in patient characteristics between the pregnancy and nonpregnancy groups. In the receiver operating characteristic curve analysis for patients aged <38 years, the value of the area under the curve was 0.77 (sensitivity, 0.83; specificity, 0.78) when optimal cutoff of RMT was 2.2 mm. There was a significant difference in preoperative RMT between the pregnancy and nonpregnancy groups (3.3 mm and 1.7 mm, respectively) in patients aged <38 years. CONCLUSION: For RMT ≥2.2 mm, hysteroscopic surgery was reasonable for secondary infertility owing to symptomatic CSD, particularly in patients aged <38 years.

Exploratory Study of Serum Lactoferrin and Anti-Lactoferrin Antibody Concentrations in Patients with Endometriosis.

Endometriosis is a disease that is characterized by the ectopic presence of the endometrium or its similar cells. A high prevalence of patients with autoimmune diseases has been reported among patients with endometriosis although the cause of endometriosis remained unknown. Recently, the anti-lactoferrin antibody is reported to be highly detected in autoimmune diseases. This study focused on lactoferrin and anti-lactoferrin antibodies to explore the pathology of endometriosis. Lactoferrin is a substance that regulates inflammation and is produced by neutrophils. Anti-lactoferrin antibody is a type of perinuclear antineutrophil cytoplasmic antibody. The serum lactoferrin and anti-lactoferrin antibody levels were compared among patients with or without endometriosis, revealing significantly higher levels in patients with endometriosis. Additionally, a decreased serum anti-lactoferrin antibody level was observed after surgical endometriosis resection. The receiver operating characteristic curve analysis determined the reference values for the serum lactoferrin and anti-lactoferrin antibody levels. Patients whose serum level exceeded the reference anti-lactoferrin antibody value were significantly higher in more than 40% of cases in the endometriosis group. The rate is comparable to that of autoimmune diseases. This is the first report that anti-lactoferrin antibody is frequently observed in patients with endometriosis, adding a new perspective to the understanding of the pathology of endometriosis although precisely elucidating the mechanism by which lactoferrin and anti-lactoferrin antibody appear in endometriosis in the future is necessary.

Transanal total mesorectal excision for primary rectovaginal carcinosarcoma: A case report and literature review.

We report a case of rectovaginal septum carcinosarcoma successfully treated with surgical excision via transanal total mesorectal excision following platinum-based neoadjuvant chemotherapy. A 48-year-old woman presented with a 3-week defecation pain preceding the visit. Pelvic imaging showed an 8-cm sized lesion in the lower rectovaginal septum. Transvaginal biopsy and immunohistochemical analysis were performed. After three courses of carboplatin-paclitaxel-bevacizumab therapy, the mass reduced by half. Subsequently, laparoscopic excision with transanal total mesorectal excision, and radical hysterectomy were performed. The anus was preserved, and dysuria improved within a month. The final histopathological diagnosis was carcinosarcoma of the rectovaginal septum from an uncertain origin, presumably endometriotic or mesonephric. Twelve months following surgery, solitary liver metastasis was confirmed; however, there was no evidence of local recurrence. Total mesorectal excision following platinum-based neoadjuvant chemotherapy may be an ideal treatment for gynecological malignancies in the rectovaginal septum, especially for large tumors localized deep into the pelvis.

Prevalence, definition, and etiology of cesarean scar defect and treatment of cesarean scar disorder: A narrative review.

Background: Cesarean scar defects (CSD) are caused by cesarean sections and cause various symptoms. Although there has been no previous consensus on the name of this condition for a long time, it has been named cesarean scar disorder (CSDi). Methods: This review summarizes the definition, prevalence, and etiology of CSD, as well as the pathophysiology and treatment of CSDi. We focused on surgical therapy and examined the effects and procedures of laparoscopy, hysteroscopy, and transvaginal surgery. Main findings: The definition of CSD was proposed as an anechoic lesion with a depth of at least 2 mm because of the varied prevalence, owing to the lack of consensus. CSD incidence depends on the number of times, procedure, and situation of cesarean sections. Histopathological findings in CSD are fibrosis and adenomyosis, and chronic inflammation in the uterine and pelvic cavities decreases fertility in women with CSDi. Although the surgical procedures are not standardized, laparoscopic, hysteroscopic, and transvaginal surgeries are effective. Conclusion: The cause and pathology of CSDi are becoming clear. However, there is variability in the prevalence and treatment strategies. Therefore, it is necessary to conduct further studies using the same definitions.

Impact of administering umbilical cord-derived mesenchymal stem cells to cynomolgus monkeys with endometriosis.

Purpose: This study aimed to explore whether umbilical cord-derived mesenchymal stem cells (UC-MSCs) could be used as a therapeutic resource for endometriosis. Methods: Of seven cynomolgus monkeys with endometriosis, five were administered UC-MSCs (intervention group) and two were administered saline (control group). First, intravenous US-MSC treatment was administered for three months. Second, weekly intravenous US-MSC administration combined with monthly intraperitoneal US-MSC administration was conducted for 3 months. Finally, weekly intraperitoneal US-MSC administration was conducted for 3 months. The dose of UC-MSCs was set to 2 × 106 cells/kg for all administration routes. Laparoscopic findings and serum cancer antigen 125 (CA125) levels were also evaluated. The Revised American Society for Reproductive Medicine classification was used for laparoscopic evaluation. Results: Laparoscopic findings showed exacerbation of endometriosis after intraperitoneal UC-MSC administration, although no changes were observed in the control group. Intravenous UC-MSC administration decreased the level of CA125 in all monkeys; however, the difference was not significant. Intraperitoneal UC-MSC administration significantly exacerbated endometriosis compared with intravenous administration (p = 0.02). Conclusions: This study revealed that intraperitoneal UC-MSC administration exacerbates endometriosis in a nonhuman primate model of the disease.

Maternal and foetal physiological response of sacral surface electrical stimulation during pregnancy: A preliminary study.

NEW FINDINGS: What is the central question of this study? The physiological response to sacral neuromodulation by pregnant women and foetuses has not been previously explored. What is the main finding and its importance? Sacral surface electrical stimulation had no adverse effect on pregnant women and foetuses at least 36 weeks of gestation. It may cause uterine relaxation resulting from decreased uterine artery pulsatility index and increased umbilical venous flow volume and thereby improve utero-placental perfusion and improve lower back pain. ABSTRACT: This study aimed to examine the impact of sacral surface electrical stimulation on maternal and foetal physiology during pregnancy. Ten pregnant women at 36 weeks of gestation without multiple gestations, foetuses with malformations, foetal growth restriction, hypertensive disorders, polyhydramnios, or oligohydramnios were enrolled. This prospective study monitored maternal and foetal physiological responses before and after sacral surface electrical stimulation for single pregnancies. Sacral surface electrical stimulation was performed once per patient. Each parameter was measured directly before and then immediately after stimulation. Follow-up measurements were conducted at 12 h, 1 day, 2 days and 7 days after stimulation. Variables of interest were compared before and after the stimulation. Regarding the foetal Doppler measurements, significant differences were not found in the umbilical and middle cerebral artery pulsatility index. However, foetuses showed a significant increase in the umbilical venous flow volume. The uterine contraction frequency and the maternal uterine artery pulsatility index significantly decreased. Pregnancy outcomes, and rates of caesarean section, foetal distress, and neonatal asphyxia were not confirmed. In conclusion, sacral surface electrical stimulation had no adverse effects on pregnant women or foetuses at 36 weeks of gestation and might improve utero-placental perfusion and lower back pain.

Atypical fetal junctional ectopic tachycardia: a case report and literature review.

BACKGROUND: Junctional ectopic tachycardia (JET) is caused by ectopic rhythms, originating in the atrioventricular node, typically with heart rate between 200 and 250 bpm. Herein, we present a case of fetal JET with normal fetal heart rate and a review of nine cases. CASE PRESENTATION: A 32-year-old, gravida 2, para 1, woman in whom fetal JET could not be diagnosed prenatally because the fetal heart rate was within the normal range. The fetus was diagnosed with premature restriction of the foramen ovale, and a cesarean section was performed, owing to the right heart overload that was characterized by fetal ascites and abnormal fetal Doppler velocity. Postnatally, the female neonate was diagnosed with JET on a 12-lead electrocardiogram, which revealed a neonatal heart rate of 158 bpm with narrow QRS and atrioventricular dissociation. After failure to respond to amiodarone therapy, she was treated with flecainide, which controlled the JET rate from 120 to 150 bpm. Fetal tachycardia with ventriculo-atrial (VA) dissociation or 1:1 VA conduction with a shorter VA interval than that of atrioventricular reentrant tachycardia confirmed the diagnosis of fetal JET. CONCLUSIONS: JET should be suspected even in the absence of tachycardia in patients with ductus venosus and pulmonary vein retrograde flow or tricuspid and mitral regurgitation without a cardiac anomaly, as tachycardia might sometimes be intermittent in cases of JET.

Increased Difficulties in Maternal Perception of Decreased Fetal Movement in Cases of Severe Fetal Growth Restriction: A Population-Based Study in Japan.

Fetal growth restriction (FGR) is defined as fetuses who have failed to achieve a normal weight for gestational age. FGR is associated with adverse perinatal outcomes, including stillbirth. Pregnant women often perceive decreased fetal movements before intrauterine fetal death. Previous reports on the association between fetal movements and FGR have mainly targeted livebirths, with few focusing on stillbirths. Studying stillbirths, not livebirths, may help improve perinatal adverse outcomes. This study evaluated the association between FGR leading to stillbirth and maternal perception of decreased fetal movement. This was a population-based study reviewing all stillbirths in Shiga Prefecture, Japan for 10 years. We analyzed 219 stillbirth cases, those with versus without FGR. We then compared maternal visits to healthcare providers due to perception of decreased fetal movement between these two groups. There were 82 stillbirths with FGR, and the remaining 137 stillbirth were without FGR. Women with FGR, compared with those without, were significantly less often to visit the outpatient department due to decreased fetal movement (30%; 25/82 vs. 46%; 63/137: P = 0.034). Pregnant women have more difficulty perceiving decreased fetal movements in cases with severe FGR than in those without FGR. Healthcare providers, including midwives, may need to closely monitor FGR pregnancy in addition to instructing pregnant women to be aware of decreased fetal movement.

Decreased Fertility in Women with Cesarean Scar Syndrome Is Associated with Chronic Inflammation in the Uterine Cavity.

Chronic inflammation in cesarean scar defect contributes to secondary infertility in women with cesarean scar syndrom; however, it remains unclear about the situation of inflammation in uterine cavity in women with cesarean scar syndrome. This ambidirectional cohort study aimed to explore the effect of inflammation in the uterine cavities of women with cesarean scar syndrome on infertility at a single university hospital. The frequency of chronic endometritis in infertile patients was retrospectively compared between the cesarean scar syndrome group and non-cesarean scar syndrome group. The frequency of endometriosis was also investigated in patients with cesarean scar syndrome who underwent laparoscopy. The level of tumor necrosis factor-α and interleukin-1ß in the uterine cavity was prospectively evaluated in the cesarean scar syndrome group and in women with a history of cesarean section (control group) using an enzyme-linked immunosorbent assay. There was a significant difference in the incidence of chronic endometritis between the cesarean scar syndrome and non-cesarean scar syndrome groups (65.8% and 46.0%, respectively, p = 0.0315). Endometriosis was detected in 51 (70%) patients with laparoscopy. Tumor necrosis factor-α and interleukin-1ß levels in the cesarean scar syndrome group were significantly higher than those in the control group (p = 0.0002 and p = 0.0217, respectively). Our findings suggest that one cause of secondary infertility in women with cesarean scar syndrome is embryo implantation failure-associated chronic endometritis, endometriosis, and chronic inflammation in the uterine cavity.

Gallbladder torsion in pregnancy: a case report and literature review.

Gallbladder torsion is a rare disease that requires immediate surgical intervention to avoid maternal and/or foetal sepsis and death. However, preoperative diagnosis is challenging because the disease has no specific symptoms. A 37-year-old pregnant woman at 34 weeks of gestation presented with severe epigastric pain. Ultrasonography and computed tomography scan findings showed a distended gallbladder without stones, floating from the hepatic bed, and laboratory examination demonstrated normal liver function; therefore, we made a diagnosis of gallbladder torsion and performed a caesarean section and an open cholecystectomy under general anaesthesia. This is the first report wherein gallbladder torsion in pregnancy was diagnosed preoperatively. Gallbladder torsion should be considered as a differential diagnosis in case of such imaging findings.

Histopathological evaluation of cesarean scar defect in women with cesarean scar syndrome.

Purpose: To explore the histopathological findings of cesarean scar defect (CSD) and the immunological component in women with cesarean scar syndrome (CSS). Methods: This retrospective study was conducted in a university hospital and a public hospital. A total of 63 patients with secondary infertility due to CSS who underwent laparoscopic resection of the CSD lesion were enrolled (CSS group), and 21 patients who underwent hysterectomy with a history of cesarean section were enrolled as control (non-CSS group). We compared the differences in histopathological findings of CSD lesions by hematoxylin and eosin staining and immunohistochemistry for CD3, CD20, CD56, CD68, CD138, myeloperoxidase, and tryptase between the two groups. Results: The frequency of presence of endometrium on the CSD surface was significantly lower (p = 0.0023) and that of adenomyosis was significantly higher (p = 0.0195) in the CSS group than in the non-CSS group. The number of CD3-, CD20-, CD68-, and tryptase-positive cells was significantly lower in the CSS group than in the non-CSS group; however, the number of CD138-positive cells was significantly higher in the CSS group (p = 0.0042). Conclusions: This study suggested that the absence of endometrium, presence of adenomyosis, and chronic inflammation in CSD contributes to secondary infertility due to CSS.

Histological diagnostic criterion for chronic endometritis based on the clinical outcome.

BACKGROUND: The diagnostic criteria of chronic endometritis remain controversial in the treatment for infertile patients. METHODS: A prospective observational study was conducted in a single university from June 2014 to September 2017. Patients who underwent single frozen-thawed blastocyst transfer with a hormone replacement cycle after histological examination for the presence of chronic endometritis were enrolled. Four criteria were used to define chronic endometritis according to the number of plasma cells in the same group of patients: 1 or more (≥ 1) plasma cells, 2 or more (≥ 2), 3 or more (≥ 3), or 5 or more (≥ 5) in 10 high-power fields. Pregnancy rates, live birth rates, and miscarriage rates of the non-chronic endometritis and the chronic endometritis groups defined with each criterion were calculated. A logistic regression analysis was performed for live births using eight explanatory variables (seven infertility factors and chronic endometritis). A receiver operating characteristic curve was drawn and the optimal cut-off value was calculated. RESULTS: A total of 69 patients were registered and 53 patients were finally analyzed after exclusion. When the diagnostic criterion was designated as the presence of ≥ 1 plasma cell in the endometrial stroma per 10 high-power fields, the pregnancy rate, live birth rate, and miscarriage rate were 63.0% vs. 30.8%, 51.9% vs. 7.7%, and 17.7% vs. 75% in the non-chronic and chronic endometritis groups, respectively. This criterion resulted in the highest pregnancy and live birth rates among the non-chronic endometritis and the smallest P values for the pregnancy rates, live birth rates, and miscarriage rates between the non-chronic and chronic endometritis groups. In the logistic regression analysis, chronic endometritis was an explanatory variable negatively affecting the objective variable of live birth only when chronic endometritis was diagnosed with ≥ 1 or ≥ 2 plasma cells per 10 high-power fields. The optimal cut-off value was obtained when one or more plasma cells were found in 10 high-power fields (sensitivity 87.5%, specificity 64.9%). CONCLUSIONS: Chronic endometritis should be diagnosed as the presence of ≥ 1 plasma cells in 10 high-power fields. According to this diagnostic criterion, chronic endometritis adversely affected the pregnancy rate and the live birth rate.

Amniotic Fluid L-Type Fatty Acid-Binding Protein in Predicting Fetal Condition.

Ultrasonography and fetal heart rate monitoring are subjective assessments of fetal condition, which warrants the need for objective markers to predict fetal condition. Urinary L-type fatty acid-binding protein (L-FABP) levels correlate with hypoperfusion. Elevated amniotic fluid L-FABP levels may represent fetal tissue hypoperfusion since the amniotic fluid contains fetal urine. In this study, we aimed to analyze the effectiveness of amniotic fluid L-FABP as a predictor of fetal condition. We classified singleton pregnancies into groups based on fetal growth restriction (FGR) with and without fetal blood flow abnormalities (FGR and healthy-FGR groups, respectively) and the non-FGR group (control group). We collected amniotic fluid at the time of vaginal delivery, cesarean section and amniocentesis, and compared the patient characteristics, clinical outcomes and amniotic fluid levels of L-FABP between the groups. We analyzed 153 singleton pregnancies and 186 amniotic fluid samples (FGR group, 6 (3.9%) pregnancies and 23 (12.4%) samples; healthy-FGR group, 15 (9.8%) pregnancies and 20 (10.7%) samples; control group, 132 (86.3%) pregnancies and 143 (76.9%) samples). The amniotic fluid L-FABP level was significantly higher in the FGR group compared to that in the healthy-FGR and control groups. Multivariate analysis revealed that the amniotic fluid L-FABP level was not affected by fetal body weight. Additionally, the amniotic fluid L-FABP levels increased significantly in cases with fetal blood flow abnormalities or early gestational age. Therefore, amniotic fluid L-FABP level may be an objective and accurate predictive marker of fetal condition.

Impact of a Psychiatric Nurse Specialist as a Liaison for Pregnant Women with Mental Disorders.

A number of scholarly reports have shown the importance of mental health care during pregnancy, especially for women with mental disorders. Nevertheless, the postpartum mortality rate due to mental disorders has been a serious issue in Japan. Therefore, since January 2015, our hospital has implemented a liaison system in which one psychiatric nurse specialist contributes to perinatal care. The aim of this study is to explore the impacts of a psychiatric nurse specialist as a liaison for pregnant women with mental disorders. More specifically, the investigation was retrospectively performed from January 2011 to December 2019 using medical records from a single university medical hospital in Japan. Participants comprised pregnant women with mental disorders. Of the 4,066 total deliveries completed during the study period, 152 women were detected as being exposed to the liaison system (2015-2019), while 92 were recognized as controls (2011-2014). We then conducted a comparative analysis between those who were exposed to the liaison system and the control group. Except for Apgar scores taken five minutes after birth, there were no intergroup differences in the patient characteristics or perinatal psychiatric outcomes. We found that the liaison system was associated with an increased rate of referral to the local public health center (p = 0.003). The system also significantly delayed the time at which patients first visited a psychiatrist because a psychiatric nurse could determine the urgency through interviews with the patients. Overall, our results suggest that the liaison system is helpful for pregnant women with mental disorders.