RESEARCH QUESTION:Is haematopoietic loss of the X chromosome (LOX), which increases with age in women, but whose reproductive relevance is unclear, associated with the likelihood of natural conception? DESIGN:Multicentre case-control study at three hospitals in Osaka, Japan. Cases were women who did not achieve natural conception after exclusion of male-factor infertility (n = 381). Controls were women who conceived naturally (n = 123). The LOX burden in peripheral blood (%LOX) was quantified by multiplex single-cell droplet digital polymerase chain reaction. Serum anti-Müllerian hormone (AMH) was measured by standardized chemiluminescent enzyme assays. The primary outcome was the difference in %LOX between cases and controls. Secondary analyses assessed assisted reproductive technology (ART) outcomes (pregnancy within three embryo-transfer cycles) among a prospectively followed subset. Exploratory analyses examined correlations of %LOX with age and AMH. RESULTS:%LOX increased with age (P < 0.001) and was higher in cases than controls (P < 0.001). This difference remained significant after adjusting for age, body mass index (BMI) and prior pregnancy (β = 0.82, 95% CI 0.70 to 0.96, P = 0.013). Receiver operating characteristic curve analysis identified an optimal %LOX threshold of 0.87% (area under the curve 0.60, 95% CI 0.54 to 0.66). Women with %LOX 0.87% or above had over twofold higher odds of not achieving natural conception (OR 2.16, 95% CI 1.40 to 3.32, P < 0.001; age-stratified, BMI-adjusted). In contrast, %LOX was not associated with pregnancy within three ART cycles (adjusted P = 0.23) and did not correlate with AMH (ρ = ‒0.06; P = 0.25) or FSH (ρ = ‒0.01; P = 0.84) levels. CONCLUSIONS:Haematopoietic LOX was associated with a lower likelihood of natural conception, whereas no clear association was found with ART outcomes was observed.

Research question Somatic loss of the X chromosome (LOX) increases with age in women, but its reproductive relevance is unclear. We asked whether hematopoietic LOX is associated with the likelihood of natural conception. Design Multicenter case–control study at three hospitals in Osaka, Japan. Cases were women who did not achieve natural conception after exclusion of male-factor infertility (n=381). Controls were women who conceived naturally (n=123). LOX burden in peripheral blood (%LOX) was quantified by multiplex single-cell droplet digital PCR developed for this study. Serum anti-Müllerian hormone (AMH) was measured by standardized chemiluminescent assays. The primary outcome was the difference in %LOX between cases and controls. Secondary analyses assessed assisted reproductive technology (ART) outcomes (pregnancy within three embryo-transfer cycles) among a prospectively followed subset. Exploratory analyses examined correlations of %LOX with age and AMH. Results %LOX increased with age and was higher in cases than controls (p<0.001). This difference remained significant after adjustment for age, BMI, and prior pregnancy (β=0.82; 95% CI, 0.70-0.96; p=0.013). ROC analysis identified an optimal %LOX threshold of 0.87% (AUC 0.60; 95% CI, 0.54-0.66). Women with %LOX ≥0.87% had over twofold higher odds of not achieving natural conception (OR=2.16; 95% CI, 1.40-3.30; p<0.001; age-stratified, BMI-adjusted). In contrast, %LOX was not associated with ART pregnancy (adjusted p=0.23) and did not correlate with AMH (ρ=-0.06; p=0.25) or FSH (ρ=-0.01; p=0.84). Conclusion In this study, hematopoietic LOX was associated with a lower likelihood of natural conception, while no clear association with ART outcomes was observed.

A complete septate uterus, resulting from the abnormal fusion of the Müllerian ducts, is a rare uterine anomaly in which the uterine cavity is divided by a septum, resulting in two separate uterine cavities. In this case, we encountered a patient with a complete septate uterus complicated by a dichorionic diamniotic twin pregnancy, with each fetus developing in separate uterine cavities. During the course of the pregnancy, the placenta of the trailing twin (Twin B) was attached to the septum. As the pregnancy progressed, the septum became progressively thinner, and Twin B exhibited growth restriction.

Objective Postpartum depression often develops within the first few months after delivery, with many cases emerging within four weeks. Although the Edinburgh Postnatal Depression Scale (EPDS) is commonly administered at one month postpartum in Japan, earlier onset highlights the need for earlier screening. This study aimed to examine the relationship between EPDS scores at postpartum day 3 and at one month, and to evaluate the predictive value of early screening. Methods We retrospectively analyzed 559 women who delivered at our hospital between January and December 2021 and attended their one-month postpartum checkup. EPDS was administered to all participants on postpartum day 3 and at one month postpartum. A cutoff of ≥9 points was used to define positivity. Correlation was assessed using Spearman's test, and receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff score on day 3 for predicting positivity at one month. Results At one month postpartum, 41 women (7.3%) were EPDS-positive. On postpartum day 3, 131 women (23.4%) were positive, of whom 22 (16.8%) remained positive at one month. Among 428 women negative at day 3, 19 (4.4%) converted to positive at one month. EPDS scores on day 3 were significantly correlated with those at one month (r = 0.476, p < 0.001). ROC analysis identified 5 points as the optimal cutoff on day 3 for predicting positivity at one month. Conclusion EPDS scores at postpartum day 3 are significantly correlated with those at one month and may help identify women at risk for postpartum depression earlier than the conventional one-month screening. Even women scoring 5-8 points at day 3, though below the traditional cutoff, showed an increased risk of later conversion and warrant careful follow-up and supportive interventions.

BACKGROUND:Postpartum hemorrhage (PPH) can lead to acute iron deficiency anemia, negatively affecting maternal health and infant care by contributing to fatigue, depression, and difficulties with breastfeeding. There is a clinical need for rapid and effective iron supplementation. OBJECTIVE:This study aimed to evaluate the real-world effectiveness of ferric derisomaltose (FDI), which allows for single high-dose intravenous administration, in comparison with conventional treatment combining intravenous and oral iron administration. METHODS:This retrospective observational study included postpartum women with hemoglobin (Hb) levels <8 g/dL within three days after delivery between April 2023 and April 2025. Patients in the FDI group received a single 1000 mg intravenous dose of FDI, while the conventional treatment group received intravenous saccharated ferric oxide and oral sodium ferrous citrate. Hematologic parameters (Hb, serum iron, total iron-binding capacity, ferritin, reticulocyte count, and serum phosphate) were evaluated at two weeks and one month postpartum. RESULTS:A total of 91 patients met the inclusion criteria (38 in the conventional treatment group and 53 in the FDI group). Hb levels were significantly higher and anemia rates significantly lower in the FDI group at both two weeks and one month postpartum. Serum iron and ferritin levels were also significantly higher in the FDI group. No cases of hypophosphatemia were observed in either group. CONCLUSION:Single-dose intravenous FDI demonstrated earlier and more effective correction of postpartum anemia compared with conventional treatment, with a favorable safety profile. FDI may represent a strong treatment option in real-world clinical practice.

BackgroundPreeclampsia (PE) is a condition in pregnancy characterized by hypertension and proteinuria, thus leading to severe complications for both mother and fetus, including fetal growth restriction (FGR). However, there are still unclear aspects regarding the pathogenesis, prevention, and treatments. This study aimed to elucidate the characteristics of lipid metabolism in maternal and umbilical cord plasma complicated with PE using liquid chromatography-mass spectrometry (LC-MS).MethodThe study included singleton pregnant women at Osaka Metropolitan University Hospital from March 2023 to February 2024. PE was diagnosed based on new-onset hypertension after 20 weeks of gestation and other symptoms such as proteinuria and organ dysfunction. FGR was defined by ultrasound measurements below -1.5 standard deviation (SD). Plasma samples were collected from maternal and umbilical cord blood within 24 hours before delivery. Lipid metabolites were comprehensively analyzed using LC-MS, and the lipokine 12,13-diHOME, identified as elevated in the comprehensive analysis, was quantified. Immunohistochemistry was conducted on placental samples to assess soluble epoxide hydrolase (sEH) expression.ResultsThe study involved 31 participants, with 20 in the control group and 11 in the PE group. A comprehensive analysis of maternal plasma samples identified a significant increase in 12,13-diHOME levels in the PE group compared to the control group. Quantification of 12,13-diHOME showed a significant increase in maternal plasma, umbilical venous plasma, and umbilical arterial plasma in the PE group compared to the control group (p = 0.007, p = 0.008, p = 0.005). PE with FGR showed significantly higher 12,13-diHOME concentrations in the umbilical arterial/venous ratio compared to the PE without FGR group (p = 0.03). Negative correlations were observed between 12,13-diHOME levels and birth weight in the PE group. Immunohistochemistry did not show significant differences in the sEH expression between the groups.ConclusionThis study demonstrated that 12,13-diHOME levels were significantly elevated in maternal and umbilical cord blood in PE patients, particularly in PE with FGR. Elevated 12,13-diHOME may reflect the progression of placental ischemia due to PE pathogenesis. This lipid metabolite could serve as a marker for the severity of preeclampsia, thus providing new insights into perinatal lipidomics and the potential role of 12,13-diHOME in PE.

Objective Immune thrombocytopenia (ITP) is frequently associated with pregnancy. However, treatment options for ITP in pregnancy are limited, and there are few animal models available for the establishment of treatments. Here, we aimed to establish a novel murine pregnant model of ITP and to investigate the impacts of thrombopoietin receptor agonist (TPO-RA) on platelet production and reproductive outcomes. Methods Anti-glycoprotein Ib-alpha (GPIbα) antibody, which binds to megakaryocytes and platelets, was subcutaneously administered to pregnant mice in order to develop an ITP model (ITP group). TPO-RA was given in doses of 1 µg/kg, 10 µg/kg, and 100 µg/kg (low-dose group, mid-dose group, and high-dose group, respectively) for the treatment of ITP in pregnancy. Results The ITP group showed a significant reduction of platelet counts of less than 15% of healthy pregnant mice (control group) and also showed a significant increase in miscarriage rate (control group, 3.8%; ITP group, 44.4%; p < 0.05). Striking increases in platelet counts were observed in every TPO-RA group without any negative effects on fetal growth and placental pathology. No abnormality was noted in the external examination of fetal mice. Interestingly, a significant recovery of miscarriage rate was observed in the mid-dose group (23.5%) compared with the ITP group (p < 0.05). Conclusion A novel ITP model in pregnant mice was induced by injection of an anti-GPIbα antibody, and sufficient effects of TPO-RA on platelet production were observed in the present study. Furthermore, the positive impacts of TPO-RA on reproductive outcomes were revealed in the ITP model.

We report the case of a woman with laminaria retention up to six years, followed by spontaneous pregnancy after the removal by hysteroscope of the intrauterine retained laminaria. A 26-year-old woman (G1P0) visited our hospital with complaints of prolonged menstrual bleeding, dyspareunia, and infertility. She had a history of dilatation and evacuation (D&E) at nine weeks of gestation six years earlier. A transvaginal ultrasound showed an artifact, and hysteroscopy revealed a long foreign body, which was suspected to be a laminaria retained after the prior abortion. In the hysteroscopic surgical procedure, the laminaria was cut, and the two halves were excised using resectoscope electrodes and hooked to the electrodes for removal. Thereafter, a year later, she conceived spontaneously and gave birth to a baby by cesarean delivery due to the arrest of labor progress. We are the first to present a pregnant case after the removal of a six-year retained laminaria.

We report a case of uterine prolapse in pregnancy, which was successfully managed before delivery. A 35year-old woman (G2P1) complained consistently of a protruding uterus at 36 weeks gestation, and an engorged uterine cervix without tenderness, urinary disturbance, and incontinence were recognized (Pelvic Organ Prolapse Quantification (POP-Q) score C: +7). Manual retraction of the edematous cervix was gently performed with gauze packing, and strikingly improved edema of the cervix with a POP-Q score of C: -2 was observed one day after the gauze packing. Induction of labor was planned due to a suspected large-forgestational-age infant, and the patient uneventfully delivered at 39 weeks gestation without any obstacles to delivery and cervical laceration. Cervical edema in pregnancy increases the risk of cervical dystocia and cervical lacerations. However, lacerations with edema are predicted to have a poor wound-healing process. The technique with gauze packing presented in this case may be useful in the protective handling of the uterine cervix during pregnancy.

Salvage human leukocyte antigen-haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide has shown promising results for graft failure in various hematological disorders. However, to our knowledge, no such findings have been reported for a case of chronic active Epstein-Barr virus infection, although graft failure is relatively common in patients with chronic active Epstein-Barr virus infection. We report a case of a 32-year-old woman with natural killer-cell type chronic active Epstein-Barr virus infection who experienced graft failure after a first allogeneic hematopoietic cell transplant from an unrelated human leukocyte antigen-matched donor.The patientreceived a second allogeneic hematopoietic cell transplant with human leukocyte antigen-haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide (cyclophosphamide, 50 mg/kg, on day 3 and day 4) following reduced-intensity conditioning as rescue therapy. Neutrophils successfully engrafted on day 19, and the patient sustained remission without severe transplant-related complication 10 months after salvage human leukocyte antigen- haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide. This report suggests that salvage human leukocyte antigen- haploidentical hematopoietic cell transplant using posttransplant cyclophosphamide may be a feasible therapeutic option for graft failure in patients with chronic active Epstein-Barr virus infection.

Objectives The aim of this study was to investigate the short-term outcomes of knotless barbed sutures used for both closures of myometrium and subcuticular tissues in patients with various operative indications and who underwent cesarean delivery (CD) in a single tertiary center. Materials and methods A retrospective cohort study was conducted, and the patients were divided into two groups. The barbed suture group consisted of patients who underwent CD using barbed sutures for uterine closure (0 Stratafix® Spiral PDS Plus, Ethicon, Somerville, NJ, USA) and subcuticular closure (4-0 Stratafix® Spiral PDS Plus). The non-barbed group consisted of patients who underwent CD using monofilament sutures for uterine closure (0-Monocryl®, Ethicon) and subcuticular closure (3-0 Opepolyx®, Alfresa, Tokyo, Japan). Results White blood cell count on post-operative day 1 was statistically lower in the barbed suture group (p=0.01), while there were no other significant differences between the two groups. Conclusion Barbed sutures can be used without major complications in patients who have undergone CD, including high-risk pregnancies.

Abstract The aims of this study were to compare the blood pressure at birth between fetal growth restriction (FGR) cases and normally grown preterm cases, and also to elucidate whether the time interval of the flow velocity waveform of ductus venosus (DV-FVW) and/or the pulsatility index of ductus venosus (DV-PI) shows a correlation with blood pressure at birth in FGR cases. FGR was defined as an estimated fetal body weight below -2.0 SD with an elevated PI of the umbilical artery (> 95 percentile). As a control group (CTL), infants matched for gestational week of delivery were selected. Doppler parameters (DV-PI and the ratio of systolic to diastolic time intervals of the DV-FVW (DV-S/D)) were measured in the FGR group within a day before delivery. The relationships were assessed between Doppler parameters and neonatal blood pressures: systolic, diastolic, and mean arterial pressure. Each blood pressure in the FGR group was lower than those in the control group. Moreover, there were significant correlations of the DV-S/D with systolic, diastolic and mean arterial pressures in the FGR group, while the DV-PI did not show any correlation with any blood pressures. The DV-S/D might be a predictive parameter for low blood pressure at birth in preterm neonates complicated with placental dysfunction.

Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical “displacement score”, indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

We aimed to investigate the relation between the time intervals of the flow velocity waveform of ductus venosus (DV-FVW) and cardiac cycles. We defined Delta A as the difference in the time measurements between DV-FVW and cardiac cycles on the assumption that the second peak of ductus venosus (D-wave) starts simultaneously with the opening of the mitral valve (MV). As well, we defined Delta B as the difference of the time measurements between DV-FVW and cardiac cycles on the assumption that the D-wave starts simultaneously with the closure of the aortic valve (AV). We then compared Delta A and Delta B in the control and fetal growth restriction (FGR) groups. In the control group of healthy fetuses, Delta A was strikingly shorter than Delta B. On the other hand, in all FGR cases, no difference was observed. The acceleration of the D-wave is suggested to be generated by the opening of the MV under normal fetal hemodynamics, whereas it precedes the opening of the MV in FGR. Our results indicate that the time interval of DV analysis might be a more informative parameter than the analysis of cardiac cycles.

Thrombopoietin receptor agonists (TPO-RAs) are an effective treatment for refractory immune thrombocytopenia (ITP). However, the use of TPO-RAs is limited for ITP in pregnant women due to concerns about fetal toxicity. In this study, we examined the effects of romiplostim, one of the TPO-RAs, on pregnant mice. The mice were injected subcutaneously with romiplostim (1, 5, 10, 30, and 100 μg/kg) on gestational days (GD) 1, 8, and 15. We evaluated maternal and fetal platelet and megakaryocyte counts (MK), fetal weight at birth, placental morphology, and miscarriage rates. Romiplostim increased platelet and MK counts in pregnant mice at all doses and in fetuses at doses above 10 µg/kg. Fetal weight at birth was slightly reduced at a dose of 100 μg/kg, but there were no significant differences in placental weight, spiral artery wall thickness, placental growth factor signal changes, or the rate of resorption at that dosage. The dose of romiplostim used clinically for ITP patients (1–10 μg/kg) did not show any adverse effects on pregnant mice. Although the results of the present study are encouraging, until there are more conclusive data, the use of romiplostim should be evaluated individually in severe, life-threatening cases, and all relevant ethical aspects should be considered.

Severe idiopathic thrombocytopenic purpura (ITP) is thought to occur in approximately one in 10,000 pregnancies and refractoriness for conventional treatment is life-threatening. We herein describe a pregnant case of refractory ITP successfully treated with eltrombopag, orally medicated thrombopoietin receptor agonist (TPO-RA). The patient was diagnosed with ITP at the age of 22 and corticosteroid, immune globulin treatments, or splenectomy was invalid. Eltrombopag was administered at 25 mg/day and the platelet count was maintained at 50-80 × 109/L. At the age of 32, she discontinued the medication out of fear of the possible adverse events of TPO-RA. She became pregnant and visited our hospital at the gestational age of 9th week with the result of a platelet count at 18 × 109/L. Two weeks later, her platelet counts further decreased to 9 × 109/L, and eltrombopag administration was resumed with 12.5 mg/day after informed written consent. The platelet counts subsequently increased and were maintained between 30 and 90 × 109/L. At 34th gestational week, the dose of eltrombopag was increased to 25 mg/day in preparation for delivery and the count increased to 123 × 109/L by the 38th gestational week. A healthy female infant weighing 2370 g was vaginally delivered by induced labor. Maternal blood loss was 0.4 L at delivery, and the newborn's platelet count was 173 × 109/L on the second day after birth and 174 × 109/L on the fifth day. The infant is neurologically and developmentally intact at 6 months of age. Regarding TPO-RA treatment for refractory ITP during pregnancy, only six pregnant cases including the present one treated with eltrombopag have been reported so far. This case is rare with reference to the use of eltrombopag for the first trimester and we increased the dose of eltrombopag at the gestational age of 34 in preparation for delivery and vaginal delivery was successful without platelet transfusion. Despite the very limited information on eltrombopag, its use might be a possible optional treatment for refractory ITP during pregnancy.

OBJECTIVE:This study aimed to investigate the accuracy and precision of continuous, non-invasive blood pressure obtained using the ClearSight system by comparing it with invasive arterial blood pressure, and to assess the hemodynamic changes using invasive methods and the ClearSight system in patients undergoing cesarean section.METHODS:Arterial pressure was measured invasively with an intra-arterial catheter and non-invasively using the ClearSight system during cesarean section in patients with placenta previa or placenta accreta. Blood pressure measurements obtained using these two means were then compared.RESULTS:Total 1,277 blood pressure measurement pairs were collected from 21 patients. Under Bland-Altman analysis, the ClearSight system demonstrated an acceptable accuracy with a bias and standard deviation of 8.8±13.4 mmHg for systolic blood pressure, -6.3±7.1 mmHg for diastolic blood pressure, and -2.7±8.0 mmHg for median blood pressure. Cardiac index levels were significantly elevated during fetal delivery and 5 minutes after placental removal, and systemic vascular resistance index levels were significantly decreased during fetal delivery and 40 minutes after placental removal.CONCLUSION:In patients undergoing cesarean section, the ClearSight system showed excellent accuracy and precision compared to that of the currently used invasive monitoring system.

Transcatheter arterial embolization (TAE) has long been reported to be safe, effective, and to have a high clinical and technical success rate for vulvovaginal hematoma. We used a permanent embolic material, diluted N-butyl-2-cyanoacrylate (NBCA), for the first choice intervention for six cases of vulvovaginal hematoma, in order to confirm the effectiveness of NBCA. Regarding post-embolization adverse events, we did not observe any fever nor necrosis or pain in the vaginal wall or vulva, in all cases. The use of NBCA as a first-line treatment for TAE of vulvovaginal hematoma is considered to be effective, in the following two ways: First, hemostasis can be achieved by adjusting the mixing ratio of NBCA and lipiodol, according to the distance between the tip of the catheter and the site of injury. Second, NBCA does not cause complications such as pain, necrosis, or infection, and it can be used safely. There are no reports clearly recommending NBCA as the first choice in the treatment of TAE for vulvovaginal hematoma. This is the first report to examine the efficacy and safety of NBCA as the first-line intervention for such cases.

We read with great interest the paper entitled "Incarcerated gravid uterus: spontaneous resolution is not rare" by Tachibana et al. [...].

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients' red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa.