Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals.

RESEARCH QUESTION: What are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles? DESIGN: A retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum. RESULTS: The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively). CONCLUSIONS: The highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.

Combination Treatment of Preoperative Embryo Cryopreservation and Endoscopic Surgery (Surgery-ART Hybrid Therapy) in Infertile Women with Diminished Ovarian Reserve and Uterine Myomas or Ovarian Endometriomas.

STUDY OBJECTIVE: To analyze the clinical outcomes of and predictive factors for the therapeutic effect of combination treatment of preoperative embryo cryopreservation and endoscopic surgery (surgery-assisted reproductive technology [ART] hybrid therapy) in infertile women with diminished ovarian reserve (DOR) with uterine fibroids and/or ovarian endometriomas. DESIGN: Retrospective cohort study. SETTING: Data from all patients who underwent surgery-ART hybrid therapy at Juntendo University Hospital and Sugiyama Clinic between 2014 and 2016 were analyzed retrospectively. We compared women who experienced live birth (success group) and implantation failure or miscarriage (failure group) after surgery-ART hybrid therapy and evaluate the predictive factors for live birth. PATIENTS: A total of 39 infertile women underwent surgery-ART hybrid therapy with 86 embryo transfer cycles. INTERVENTIONS: All women underwent ART treatment for embryo cryopreservation preoperatively, reproductive surgery, and warmed embryo transfer after the postoperative contraceptive interval (surgery-ART hybrid therapy) for women with DOR (anti-Müllerian hormone <1.0 ng/mL) and/or advanced reproductive age (>40 years) with uterine myomas and/or ovarian endometriomas who required surgery. RESULTS: Among 39 women underwent surgery-ART hybrid therapy, 1 woman acquired no embryo after oocyte retrieval trials and abandoned efforts to conceive, 14 experienced childbirth (success group) and 24 (63.2%) experienced implantation failure or miscarriage (failure group) after surgery-ART hybrid therapy. The median patient age was 40 years (interquartile range [IQR], 38-41 years) in the success group and 41.5 years (IQR, 41-42 years) in the failure group (p = .032). The respective serum anti-Müllerian hormone levels were 2.5 ng/mL (range, 0.1-8.6 ng/mL) and 1.3 ng/mL (range, 0.1-4.2 ng/mL) (p = .396), and the respective numbers of preoperative frozen were 5.0 (range, 4.0-6.0) and 2.0 (range, 1.0-3.0) (p < .001). There were no significant differences in surgical findings of myomas and endometriosis between the 2 groups. Compared with the 24 women who experienced hybrid therapy failure, the 14 who underwent successful surgery-ART hybrid therapy were significantly younger and had a greater number of cryopreserved embryos. CONCLUSION: Successful surgery-ART hybrid therapy requires a sufficient preoperative age-specific number of frozen embryos, establishment of ART treatment with stable pregnancy outcomes and skillful reproductive surgery, and a strong desire of the patient and doctor for pregnancy.

Enclosing sutures technique for control of local bleeding in a case of placenta increta.

Antepartum diagnosis of uterine placenta increta is difficult, thus considering a counterplan during placental delivery is obliged. Uterine compression suture is one of the choices of hemostatic surgical techniques for postpartum hemorrhage. However, uterine synechiae/ischemia are known for the complications. To avoid these complications, we performed a novel hemostatic suture with a contrivance for a case of uterine posterior placenta increta. A nullipara with a history of multiple intrauterine operation underwent cesarean delivery. She was diagnosed as placental increta, and most of the placenta was removed manually. Because continuous bleeding from attachment site was observed even with a balloon tamponade test, four single sutures pierced only the uterine posterior wall with deliberate gaps to each knot were placed to enclose bleeding area. Hemostasis was accomplished without blood transfusion or hysterectomy. This novel hemostatic technique has the potential to control local bleeding without excessively reducing uterine blood flow.

The characteristics of healthy adults with hardly palpable vein--Relations between easy venous palpation and physical factors.

This study aimed to investigate relations between ease of venous palpation and various venous factors, and to elucidate characteristics of hardly palpable veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous palpation was scored from 0: impalpable to 3: well palpable. Venous factors, namely venous depth, elevation, area and minimal pressure that starts to collapse vein, were measured using an ultrasonography before and after tourniquet inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the venous area and venous palpation score. The four venous factors correlated significantly with venous palpation score with the following correlation coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to-collapse pressure (-0.220). The characteristics of hardly palpable veins were small size, deep location and little elevation. Although vasodilatation facilitated venous palpation, venous depth and elevation were also important and should be included in future studies in which vasodilatation methods are evaluated.

Routine patient assessment and the use of patient-reported outcomes in specialized palliative care in Japan.

BACKGROUND: Discrepancies in symptom assessment between providers and patients are reported in cancer care, and the use of patient-reported outcome measures (PROMs) has been recommended for patients receiving palliative care. However, the status of the routine use of PROMs in palliative care in Japan is presently unclear. Therefore, this study aimed to clarify this complex question. To this end, we administered a questionnaire survey either online or via telephone interviews (questionnaire: sent to 427 designated cancer hospitals, 423 palliative care units [PCUs], and 197 home hospices; interviews: conducted at 13 designated cancer hospitals, nine PCUs, and two home hospices). RESULTS: Questionnaires were returned from 458 institutions (44% response rate). We found that 35 palliative care teams (PCTs, 15%), 66 outpatient palliative care services (29%), 24 PCUs (11%) and one (5%) home hospice routinely used PROMs. The most frequently implemented instrument was the Comprehensive Care Needs Survey questionnaire. Moreover, 99 institutions (92%) that routinely used PROMs responded these instruments as useful in relieving patients' symptoms; and moreover, the response rate in regard to usefulness in symptom management was higher than that of institutions that did not routinely use PROMs (p = 0.002); > 50% of the institutions that routinely used PROMs stated that use of these instruments was influenced by disease progression and patients' cognitive function. Moreover, 24 institutions agreed to be interviewed, and interviews demonstrated the benefits of and the barriers to the implementation of PROMs. Effective methods used in the implementation of PROMs were introduced as efforts to reduce the burden placed on patients and to promote healthcare providers' education in the use of PROMs. CONCLUSIONS: This survey quantified the status of the routine use of PROMs within specialized palliative care in Japan, revealed barriers to wider PROM use, and identified needed innovations. Only 108 institutions (24%) routinely used PROMs within specialized palliative care. Based on the results of the study, it is necessary to carefully consider the usefulness of PROs in clinical palliative care, perform careful selection of PROMs according to the patient's condition, and evaluate how specifically to introduce and operate PROMs.

A case of 46,XY complete gonadal dysgenesis with a novel missense variant in SRY.

Disorders of sex development (DSD) with mild external genital abnormalities may be diagnosed after puberty. Here, we report a case of 46,XY complete gonadal dysgenesis with a novel missense variant in sex-determining region Y (SRY), diagnosed after primary amenorrhea. A 15-yr-old patient presented to our gynecology department with a chief complaint of amenorrhea. The patient was diagnosed with a 46,XY karyotype, and SRY gene positivity. Gonadotropin levels were high, whereas testosterone levels were low. A pelvic magnetic resonance imaging (MRI) revealed a hypoplastic uterus; however, no gonads could be identified. Laparoscopy revealed bilateral streak gonads, fallopian tube-like structures, and the uterus. The gonads were removed based on the risk of gonadal malignancy. Comprehensive genetic analysis of DSD revealed a previously unreported SRY variant, c.271A>T, p.Ser91Cys, and in silico analysis predicted the variant to be pathogenic. The patient was diagnosed with 46,XY complete gonadal dysgenesis with a novel missense variant in SRY. The patient continued female hormone replacement therapy and experienced breast enlargement and cyclic menstruation. Determining the etiology of DSD can be difficult, causing anxiety in patients and their families. In addition to surgical scrutiny, genetic analysis is important to aid in diagnosis and reassure patients and their families.

Validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients.

AIM: This study assessed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients. METHODS: We recruited 223 non-cancer patients receiving palliative care and their healthcare providers (222) across two home care facilities and two hospitals for a cross-sectional study. We assessed the construct validity and known-group validity of the Integrated Palliative Care Outcome Scale. The weighted kappa and interclass correlation coefficients were assessed to ascertain reliability. RESULTS: The scale scores were significantly higher for the 'non-stable' group (worsening condition group) measured in the palliative care phase than for the 'stable' group (P < 0.001). Regarding validity, Spearman's correlations between similar items on the Integrated Palliative Care Outcome Scale and Edmonton Symptom Assessment System ranged from 0.61 to 0.94. Regarding reliability, the weighted kappa coefficients ranged from 0.53 to 0.81 for patients and from 0.58 to 0.90 for healthcare providers. For inter-rater reliability between patients and healthcare providers, the weighted kappa coefficients for each item ranged from 0.03 to 0.42. CONCLUSION: This study confirmed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients requiring palliative care. However, the inter-rater reliability indicates poor agreement between the assessments of patients and healthcare providers. This highlights the discrepancies between both their assessments and the importance of the patient's assessment. Geriatr Gerontol Int 2023; 23: 517-523.

Relationship between tourniquet pressure and a cross-section area of superficial vein of forearm.

This study investigated the appropriate tourniquet pressure (TP) and duration of tourniquet application for venipuncture by calculating the venous cross-section (VCS) area on ultrasonography. Twenty healthy volunteers without cardiovascular risk factors were enrolled in this study. A target vein (either a cephalic or median cubital vein) was selected on ultrasonography. The pneumatic tourniquet was inflated using a rapid cuff inflator system at setting pressure for 120 sec. TP strength was varied from 20 mmHg to 100 mmHg, in 20 mmHg increments. The order of TP was randomized. Comparisons among more than 3 groups were performed by one-way repeated-measures ANOVA and the Bonferroni method. The VCS area increased rapidly until 10 sec after tourniquet inflation. The VCS area then increased gradually until 30 sec after tourniquet inflation. After that, the VCS area did not increase remarkably. The VCS area increased with TP strength up to 80 mmHg, but the VCS area at TP 100 mmHg decreased to less than that at TP 40 mmHg. Based on these results, we recommend a tourniquet pressure of 60 mmHg, and duration of tourniquet application is 30 to 60 sec for venipuncture.

Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio.

PROBLEM: We aimed to assess whether an imbalance of T-helper (Th) 1 and Th2 cells contributes to implantation failure and pregnancy loss. METHOD OF STUDY: In this cross-sectional study, 197 consecutive patients with a history of repeated implantation failure (RIF) after three or more embryo transfer (ET) cycles and/or recurrent pregnancy loss (RPL) after two or more clinical pregnancy losses underwent Th cell testing. After excluding 42 women aged ≥44 and 9 with vitamin D supplementation, we recruited 146 women including 79 with RIF and 81 with RPL. Fourteen women had a history of both RIF and RPL. We also recruited 45 fertile women and 40 general infertile women without a history of in vitro fertilization treatment. This study was approved by the local ethics committee. RESULTS: There was no significant difference in IFN-γ-producing Th1 and IL-4-producing Th2 cell levels between the fertile and general infertile women, but Th1 cell levels and the Th1/Th2 cell ratio were significantly higher in the women with ≥4 ET cycles and ≥2 pregnancy losses than in the fertile and general infertile women. In the general infertile women, the total livebirth rates including natural conception after two ET cycles in the normal and high Th1/Th2 groups (Th1/Th2 <11.8 and ≥11.8, respectively) were 66.7% and 87.5%, respectively (p = .395). CONCLUSIONS: A high Th1/Th2 cell ratio was linked to ≥4 implantation failure cycles and ≥2 pregnancy losses but not to general infertility.

Analysis of the risk factors and treatment for repeated implantation failure: OPtimization of Thyroid function, IMmunity, and Uterine Milieu (OPTIMUM) treatment strategy.

PROBLEM: What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)? METHOD OF STUDY: Infertile women with a history of RIF after more than three embryo transfer (ET) cycles underwent implantation testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25-hydroxyvitamin D3 , interferon-γ-producing helper T (Th1) cell, IL-4-producing helper T (Th2) cell, thyroid-stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening between April 2017 and August 2018. We treated chronic endometritis with antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus intake, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of the 116 RIF women, 88 women with 133 ET cycles were recruited from a questionnaire-based survey regarding pregnancy outcomes. Fifty-nine consecutive RIF patients without the OPTIMUM treatment strategy were also recruited as a control. RESULTS: The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3-19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control. CONCLUSIONS: The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.

Sex differences in factors associated with poor subjective sleep quality in athletes.

BACKGROUND: Sleep is an important recovery period for athletes. In general, women are not satisfied with their sleep quality, which is also true for female soccer players, although the reasons remain to be elucidated. This study aimed to confirm sex difference in sleep quality among athletes from various fields of sport, and to investigate factors related to poor subjective sleep quality in male and female athletes. METHODS: We collected data concerning subjective sleep quality, measured by Pittsburgh Sleep Quality Index (PSQI), from athletes who were 16 to 40 years of age and played various types of sports. Data concerning their sports, lifestyle, and sleep issues and sleep environments, and also menstrual issues for females, were collected. RESULTS: Data from 207 male athletes and 215 female athletes were assessed. Among them, 31.4% of men and 48.8% of women had poor subjective sleep quality (i.e., PSQI≥6). In male athletes, witnessed apnea, episodes of disorientation or confusion during the time of sleep, long time gap between dinner and bedtime, and turning on the heating in the winter, were identified as factors associated with poor sleep quality by multivariate analysis, whereas in female athletes, bathing close to bedtime, habitual drinking, and being annoyed by noises at bedtime were identified. CONCLUSIONS: In both populations, females had poorer subjective sleep quality than males. Sex differences exist in factors associated with poor subjective sleep quality. Thus, different approaches should be considered to improve their sleep quality.

Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity.

Emerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. However, whether tumor-associated stroma induces epithelial-mesenchymal plasticity in tumor cell clusters, to promote invasion and metastasis, remains unknown. We demonstrate herein that carcinoma-associated fibroblasts (CAFs) frequently present in tumor stroma drive the formation of tumor cell clusters composed of two distinct cancer cell populations, one in a highly epithelial (E-cadherinhiZEB1lo/neg: Ehi) state and another in a hybrid epithelial/mesenchymal (E-cadherinloZEB1hi: E/M) state. The Ehi cells highly express oncogenic cell-cell adhesion molecules, such as carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and CEACAM6 that associate with E-cadherin, resulting in increased tumor cell cluster formation and metastatic seeding. The E/M cells also retain associations with Ehi cells, which follow the E/M cells leading to collective invasion. CAF-produced stromal cell-derived factor 1 and transforming growth factor-ß confer the Ehi and E/M states as well as invasive and metastatic traits via Src activation in apposed human breast tumor cells. Taken together, these findings indicate that invasive and metastatic tumor cell clusters are induced by CAFs via epithelial-mesenchymal plasticity.