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.

The effects of chronic endometritis on the pregnancy outcomes.

PROBLEM: Chronic endometritis (CE) influences the clinical outcomes of assisted reproductive technology. However, the effect of CE on the pregnancy outcome is still unknown. METHOD OF STUDY: A retrospective case-control study was conducted in a single university. Subjects who conceived by in vitro fertilization within a year after a histological diagnosis of CE under 40 years of age from September 2013 to December 2017 were extracted. The rates of miscarriage, preterm birth, term birth, and live birth per pregnancy according to the presence or absence of CE were analyzed. A logistic regression analysis was performed for miscarriage, preterm birth, term birth, and live birth for eight explanatory variables of seven infertility factors and CE. RESULTS: A total of 39 pregnancies in 38 subjects with non-CE and 35 pregnancies in 32 subjects with CE were ultimately analyzed. The rates of miscarriage, preterm birth, term birth, and live birth per pregnancy were 12.8% and 40.0% (P < .03), 2.6% and 14.3% (P = .1), 84.6% and 45.7% (P < .001) and 84.6% and 57.1% (P < .03) in the Non-CE and CE groups, respectively, although only the analysis for tem birth rate had sufficient power to exclude Type II error. In logistic analysis, CE was a factor affecting the objective variables of miscarriage, term birth, and live birth. CONCLUSIONS: The term birth rate among pregnancies decreased mainly due to an increase in miscarriages when CE was detected before pregnancy in patients treated with in vitro fertilization. A histopathological diagnosis of CE adversely affected the term birth rate per pregnancy.

Relationship of chronic endometritis with chronic deciduitis in cases of miscarriage.

BACKGROUND: The presence of chronic deciduitis (CD) was determined in patients diagnosed with or without chronic endometritis (CE) before pregnancy. OBJECTIVE: To study the effect of CE on decidua in cases of miscarriage. METHODS: Decidual tissue was obtained from the patients who miscarried at the first pregnancy within a year after the diagnosis of the presence or absence of CE. The number and distribution pattern of plasma cells stained with CD138 in decidual tissue in 10 high-power fields (HPFs) was examined. The prevalence of CD diagnosed with four different grade; grade 0, no plasma cell in 10 HPFs, thus Non-CD;grade 1, rare single plasma cells; grade 2, rare clusters or more than 5 single cells total; and grade 3, many plasma cells with more than 5 clusters, were examined and compared between Non-CE and CE. RESULTS: The incidence rate of CD of grade2 + 3 was significantly higher in CE than Non-CE (53.8%; 7/13 vs. 0%; 0/13, P < 0.01). Presence of clusters or a number of plasma cells in 10 HPFs of decidua showed a sensitivity of 53.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68.4% for the diagnosis of CE. CONCLUSION: Presence of clusters of plasma cells or five or more of plasma cells in decidua was found in more than half of CE, but not found in Non-CE. When CD with cluster or five or more of plasma cells is confirmed histologically in miscarriage decidual tissue, the presence of CE before the pregnancy should be suspected.

Endometrial Immunity for Embryo Implantation and Pregnancy Establishment.

The uterus is an organ for raising the fetus, and its lumen is lined by the endometrium. The endometrium is an important site for the implantation and maturation of fertilized eggs. The endometrium undergoes repetitive proliferation, maturation (decidualization), and exfoliation changes every menstrual cycle. At the same time, the number and type of endometrial immunocompetent cells vary during the menstrual cycle. At the implantation stage, the immunocompetent cells occupy approximately half of the endometrial cells. Immunocompetent cells normally eliminate pathogenic microorganisms to protect the body; however, they also promote immune tolerance to accept the fetus during pregnancy. The immunocompetent cells in the uterus can perform both these functions. With the establishment of pregnancy, stimuli from the trophoblast (placenta) and fetus can also change the immune environment of the uterus, and pregnancy can be maintained only when the immune system is well adapted to the stimuli of some hormones and the fetus. Immunity for the establishment of pregnancy is not simple because multiple immunocompetent cells are involved in establishing and maintaining pregnancy. To understand the immune mechanisms associated with the establishment of pregnancy, we have to learn about each immune cell. This review, therefore, discusses the roles and distribution of the immunocompetent cells inside the uterus during menstruation and early pregnancy.

Review: Chronic endometritis and its effect on reproduction.

AIM: Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE. METHODS: The published articles were reviewed. RESULTS: The prevalence of CE has been found to be 2.8-56.8% in infertile women, 14-67.5% in women with recurrent implantation failure (RIF), and 9.3-67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE. CONCLUSION: CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.

Protective effect of a mechanistic target of rapamycin inhibitor on an in vivo model ofcisplatin-induced ovarian gonadotoxicity.

This study aimed to evaluate the protective effect of everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, on cisplatin chemotherapy-induced ovarian toxicity. Eighty sexually mature, virgin, female, 7-week-old C57BL/6J mice were divided into four groups: control, cisplatin (Cis), everolimus (mTORi), and everolimus plus cisplatin (mTORi+Cis). Mice in the Cis and mTORi+Cis groups were intraperitoneally injected with 2 mg/kg of cisplatin for 15 d. Mice in the mTORi and mTORi+Cis groups were orally administered 2.5 mg/kg of everolimus for 29 d, from one week before the first cisplatin injection to one week after the last cisplatin injection. Histological examinations were performed 24 h after the last everolimus administration. The primordial, primary, and antral follicles were significantly depleted in the Cis group compared with that in the control group, confirming the gonadotoxicity of cisplatin. The number of primordial, secondary, and antral follicles was significantly higher in the mTORi+Cis group than in the Cis group, thereby displaying the effect of mTORi-treatment on ovarian protection. Primordial, secondary, and antral follicle counts were similar in the mTORi+Cis and the control groups. The results of this study indicate a protective effect of an mTOR inhibitor against cisplatin chemotherapy-induced gonadotoxicity in the ovarian reserve in an in vivo mouse model.

Management of ureteral stenting for postrenal failure during pregnancy after ureteral reimplantation: a case report.

BACKGROUND: Vesicoureteral reflux is thought to predispose to urinary tract infection and renal scarring, and ureteral reimplantation in childhood remains the gold standard for its treatment. It has been reported that the risk of postrenal failure during pregnancy is increased among women with Politano-Leadbetter ureteral reimplantation. In previous case reports on patients with progressive hydronephrosis and renal failure during pregnancy after ureteral reimplantation, percutaneous nephrostomy was always required, so there has been no information about the clinical management of such patients by ureteral stenting. Here we report a patient with a history of bilateral ureteral reimplantation, in whom severe hydronephrosis during pregnancy was managed with ureteral stents. CASE PRESENTATION: A primigravida with severe hydronephrosis was referred to us at 29 weeks of gestation. Bilateral Politano-Leadbetter ureteral reimplantation had been performed at the age of 3 years. She was hospitalized immediately, and bilateral ureteral stents were successfully inserted. Post-obstructive diuresis occurred after the stents were placed. Urinary tract infection developed after removal of the urethral catheter 1 week later, but responded to antibiotic therapy and catheter replacement. Labor was induced at 39 weeks of gestation, with vaginal delivery of a healthy male infant. Both stents were found to have spontaneously migrated into the urethra after delivery. Repeat stenting under spinal anesthesia was required to improve postpartum symptoms of back pain and fever. Right distal ureteral obstruction persisted at 6 months after delivery and repeat ureteral reimplantation is planned. CONCLUSIONS: General obstetricians will not necessarily pay attention to a history of Politano-Leadbetter ureteral reimplantation, but these patients should undergo careful monitoring of renal function and urinary tract morphology during perinatal care. In the present case, ureteral stenting was effective for postrenal failure during pregnancy after ureteral reimplantation. If ureteral stenting is selected, attention should be paid to post-obstructive diuresis, infection, and stent migration.

Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review.

Progressive fetal growth restriction (FGR) is often an indication for delivery. In dichorionic diamniotic (DD) twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR), the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks) before 30 weeks of gestation. The interval from growth arrest to delivery was 21-24 days and the discordance was 33.7-49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus.

Exaggerated placental site, consisting of implantation site intermediate trophoblasts, causes massive postpartum uterine hemorrhage: case report and literature review.

Every year, 14 million cases of obstetric hemorrhage occur worldwide, causing 127,000 maternal deaths. About 75% of postpartum hemorrhage cases are due to atonic uterus, which is loss of uterine muscular tone or strength for contraction of the uterus after delivery. The prediction of atonic uterus is therefore important for the prevention of postpartum maternal death. However, prediction of occurrence of atonic uterus is difficult before delivery, because the precise pathophysiological mechanism to trigger this condition remains unclear. Here, we present a case of severe postpartum hemorrhage due to atonic uterus. A 35-year-old woman gave a birth by vaginal delivery to a healthy boy. However, due to intractable massive hemorrhage after the removal of the retained placenta, we performed supravaginal hysterectomy as the best option for survival. Pathological examination showed that implantation site intermediate trophoblasts (ISITs) formed unusually large clumps in the decidua, diagnosed as exaggerated placental site (EPS). EPS is thought to be a condition consisting of an excessive number of ISITs. ISITs are differentiated from a trophoblast lineage in the process of placenta formation. ISITs anchor the placenta to the maternal tissue and are considered to maintain pregnancy, but the postpartum role of these cells remains unclear. Excessive infiltration of ISITs, namely EPS, may cause postpartum atonic uterus. In this article, we also reviewed the literatures on EPS. The present case and other reported cases indicate that EPS causes mass formation in the uterus, continuous uterine bleeding, and massive hemorrhage, resulting in hysterectomy.

Timing of cisplatin administration for chemoradiotherapy in transgenic mice bearing lens tumors.

Cisplatin-based concurrent chemoradiotherapy (CCRT) has become a standard treatment for cancer of the uterine cervix. However, there have been no investigations into the optimum timing for administration of anticancer drugs using animal models. The aim of the present study was to determine the appropriate timing for administration of the anticancer drug cisplatin in relation to delivery of radiation by assessing the antitumor activity and adverse effects of 3 different regimens in αT3 transgenic mice bearing lens epithelial tumors. CCRT showed the strongest antitumor activity. There was a significant difference between CCRT and administration of cisplatin before radiotherapy (neoadjuvant therapy) with regard to the apoptotic effect detected by TUNEL staining, but there was no significant difference between CCRT and administration of cisplatin after radiotherapy (adjuvant therapy). Assessment of adverse effects showed that there were no significant differences in the mortality rate, weight loss, anemia and leukopenia among the 3 regimens. In conclusion, these findings obtained in an animal model suggest that cisplatin should probably not be administered before irradiation, since the antitumor effect is significantly weaker than that of CCRT or administration after irradiation, while adverse effects are similar.

Successful delivery following ICSI with macrocephalic sperm head syndrome: a case report.

This article reports a case of macrocephalic sperm head syndrome, which is defined as the presence of a very high percentage of spermatozoa with enlarged heads and multiple flagellae, together with detailed morphological analysis. After a couple presented with infertility, sperm analysis showed severe teratozoospermia and almost all of the spermatozoa had macrocephaly with multiple tails. The morphological analysis revealed that most of the sperm heads contained several nuclei and had a similar number of tails as that of nuclei. However, detailed analysis revealed that there were a very few spermatozoa with an almost normal morphology. After genetic counselling, intracytoplasmic sperm injection was performed using a few spermatozoa that had an almost normal morphology, resulting in pregnancy and successful delivery. Even in macrocephalic sperm head syndrome, which may be caused by meiotic division failure, pregnancy is possible if some spermatozoa with almost normal morphology can be utilized, although there may be genetic risks.

A case of serous endometrial intraepithelial carcinoma with p53 positivity for six years.

A 69-year-old postmenopausal woman was referred because she had been taking tamoxifen for four years. Tissues obtained by endometrial curettage were immunopositive for p53, but there was no definite malignancy. At age 73, cytology again showed abnormalities, so we repeated complete endometrial curettage. Again, there was no malignancy, but p53 immunostaining was widely positive. At age 75, hysterectomy was performed because cytological examination showed increasingly abnormal findings and the patient opted for surgery. In the resected uterus, endometrial glands were replaced by malignant cells resembling papillary serous carcinoma cells with high-grade nuclei, but there was no stromal or myometrial invasion. The pathological diagnosis was intraepithelial serous endometrial carcinoma. This is a rare case because we could follow the patient for 6 years by endometrial cytology or endometrial curettage and we observed gradual transformation into endometrial intraepithelial carcinoma.

Change of salivary stress marker concentrations during pregnancy: maternal depressive status suppress changes of those levels.

AIM: The aim of the present study was to show changes in salivary cortisol and chromogranin A/protein concentrations as stress markers during pregnancy and to clarify the effect of chronic stress on stress markers. MATERIAL AND METHODS: Salivary samples were collected from 69 pregnant women during pregnancy. Salivary cortisol levels and chromogranin A/protein titers were determined. We surveyed the women's chronic stress using the Zung self-rating depression scale and General Health Questionnaire-28. RESULTS: Cortisol levels in the saliva of pregnant women showed biphasic change during pregnancy. Chromogranin A/protein levels in the saliva of pregnant women increased in the second and the early third trimesters and decreased to the puerperal period. Salivary cortisol concentrations of the chronic high stress group were significantly lower compared with those of the normal group. Salivary chromogranin A/protein concentrations of the chronic high stress group were also significantly lower than those of the normal group. CONCLUSION: The titration of salivary cortisol concentrations and chromogranin A/protein levels is a useful tool to determine maternal stress levels. The elevation of cortisol and chromogranin A/protein in the saliva was suppressed in the chronic high stress group during pregnancy.

Long-term cumulative pregnancy rate in women with unexplained infertility after laparoscopic surgery followed by in vitro fertilization or in vitro fertilization alone.

AIMS: Laparoscopy has been performed in women with unexplained infertility, but the recent trend is to commence in vitro fertilization (IVF) without prior laparoscopy. The aim of this study was to determine whether or not laparoscopic surgery is necessary for these patients. MATERIAL & METHODS: With a diagnosis of unexplained infertility, 51 women underwent laparoscopic surgery followed by IVF (laparoscopy group) and 41 women underwent IVF without prior laparoscopy (IVF group). We reviewed these two groups retrospectively and evaluated the cumulative pregnancy rate. RESULTS: In the laparoscopy group, 16 of the 51 women became pregnant spontaneously soon after surgery. Twenty-three patients became pregnant with IVF. In the IVF group, 32 patients became pregnant with IVF. Two of the 41 women became pregnant spontaneously while waiting to commence IVF. CONCLUSION: Laparoscopy should be offered as an option for younger patients who desire spontaneous pregnancy because there was no significant difference of the cumulative pregnancy rate between the groups.

Three-dimensional computed tomography combined with hysterosalpingography is useful for both diagnosis and treatment of iatrogenic diverticulum of the uterus.

A woman presented with vaginal bleeding after myomectomy. Ultrasonography, magnetic resonance imaging (MRI), and three-dimensional computed tomography (CT) combined with hysterosalpingography (HSG) revealed an iatrogenic diverticulum of the uterus. The three-dimensional CT combined with HSG images were very useful for subsequent surgery.

Neoadjuvant intraarterial chemotherapy for stage IIB-IIIB cervical cancer in Japanese women.

Chemoradiotherapy is currently the main treatment for locally advanced cervical cancer, but neoadjuvant intraarterial chemotherapy (IA-NAC) has been reported to achieve favorable results. This study investigated the efficacy of several different IA-NAC regimens. The subjects were 55 patients with stage IIB-IIIB cervical cancer who received IA-NAC between January 1991 and April 2006. IA-NAC was administered for a total of 1-3 courses at 3-week intervals, with three different regimens being employed in chronological order. The response rate achieved with IA-NAC was 90.2% for squamous cell carcinoma, 60% for adenosquamous carcinoma and 42.9% for adenocarcinoma. Surgery was performed after IA-NAC in 36 patients, and radiotherapy alone was performed in 19 patients. The 5-year survival rate was 72.9% for patients with squamous cell carcinoma and 50% for those with adenocarcinoma or adenosquamous carcinoma. PAMF therapy (cisplatin, epirubicin, mitomycin-C and 5-fluorouracil) achieved a response rate of ≥90% for squamous cell carcinoma, as did CDDP + THP therapy (cisplatin plus pirarubicin), while PACF therapy (cisplatin, epirubicin, cyclophosphamide and 5-flurouracil) achieved a better response rate for adenosquamous carcinoma and adenocarcinoma. Grade 3 or 4 hematological toxicity was significantly more common with PAMF therapy. In conclusion, IA-NAC improved the survival of patients with squamous cell carcinoma. CDDP + THP therapy achieved a high response rate with little hematologic toxicity. PACF therapy achieved a significantly higher response rate in patients with adenosquamous carcinoma or adenocarcinoma. Therefore, IA-NAC may be a therapeutic option for locally advanced cervical cancer, particularly using the above-mentioned regimens.

A unique fibrous tumor of the ovary: fibrosarcoma or mitotically active cellular fibroma?

A unique fibrous tumor of the ovary is reported. A 32-year-old nulliparous woman was diagnosed with a left ovarian tumor and underwent left salpingo-oophorectomy. Macroscopically, the cut surface of the tumor showed yellowish multilobular areas. There was no sign of necrosis or hemorrhage within the tumor. Microscopically, the tumor consisted of two well-circumscribed components. One corresponded to the yellowish lobular areas; there were more than 10 mitotic figures per 10 high-power fields and strong staining for Ki-67, suggesting fibrosarcoma, but nuclear atypia was not severe. In the other component, there were few if any mitotic figures; there was no nuclear atypia and marked cellularity. Pathologically, the tumor was considered a variant fibrosarcoma or a mitotically active cellular fibroma. In light of these pathological findings along with the patient's age and obstetrical history, no further treatment was performed. There has been no evidence of recurrence after 1-year follow-up.