Spontaneous Pregnancy After the Removal of Long-Term Retained Laminaria.

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.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

The Impact of Assisted Reproductive Technology on Umbilical Cord Insertion: Increased Risk of Velamentous Cord Insertion in Singleton Pregnancies Conceived through ICSI.

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.

Barbed Sutures and Their Potential Role in Reducing Inflammatory Reaction After Cesarean Delivery: A Single-Center Experience.

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.

Exploring the Impact of Endometrioma Aspiration and Dienogest Combination Therapy on Cyst Size, Inflammatory Cytokines in Follicular Fluid and Fertility Outcomes.

Endometriomas (chocolate cysts) are cystic lesions that can develop on ovaries, and are characterized by the presence of ectopic endometrial tissue or similar tissue. Such lesions can cause a decline in the number and quality of oocytes, and lead to implantation failure. In this study, we retrospectively assessed the efficacy of repeated endometrioma aspiration and dienogest combination therapy in patients suffering endometriosis-associated infertility with endometriomas. A comparison was made between a treated group that underwent combination therapy followed by controlled ovarian hyperstimulation (COH) (n = 30) and a control group that did not undergo treatment (n = 40), at the IVF Osaka Clinic from September 2019 to September 2021. There were no differences in patient background between the two groups. A reduction in endometrioma size continued for 12 months after treatment. The numbers of follicles that developed to 15 mm or greater in size following COH and mature oocytes were significantly lower in the treated group compared to those in the control group. The levels of inflammatory cytokines in the follicular fluid significantly decreased in the treated group (p < 0.05). In patients in the treated group who underwent a second ova retrieval, the results were compared between those in the first ova retrieval (immediately after the end of treatment) and those in the second ova retrieval (four months after the first retrieval). The numbers of follicles following COH, retrieved, mature and fertilized ova were significantly increased in the second ova retrieval.

Salvage Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplant With Posttransplant Cyclophosphamide for Graft Failure in a Patient With Chronic Active Epstein-Barr Virus Infection.

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.

Changes of Coagulation and Fibrinolytic Status Detected by Thromboelastography (TEG6s®) in Pregnancy, Labor, Early Postpartum, Postpartum Hemorrhage and Heparin Treatment for Perinatal Venous Thrombosis.

The aims of this study are to evaluate coagulation and fibrinolytic features using TEG6s® in normal pregnant courses, in the early postpartum period and in cases with postpartum hemorrhage (PPH) caused by uterine atony. We also analyze cases with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) under treatment with unfractionated heparin. The non-pregnant women (n = 13) and healthy pregnant women (at 9-13 weeks of gestation (n = 13), at 27-30 weeks of gestation (n = 14), at 35-38 weeks of gestation (n = 14)) were cross-sectionally studied, while the normal pregnant women at delivery (n = 14) were sequentially investigated. Blood samples from those patients with PPH (n = 15) and DVT and/or PE (n = 11) were also obtained and compared with those of normal women. Significant changes of clot formation parameters were observed in all parameters and, interestingly, fibrinolytic parameter (LY30) was maintained at a low value even within 120 min after placental delivery (median of LY30; 0) and also in cases with uterine atony (median of LY30; 0.1). The parameter that indicates the effectiveness of heparin showed strong correlation (R = 0.788) with activated partial thromboplastin time. Thromboelastography may be less sensitive to fibrinolysis in the conditions of uterine atonic bleeding.

The Hematopoietic Effect of Ninjinyoeito (TJ-108), a Traditional Japanese Herbal Medicine, in Pregnant Women Preparing for Autologous Blood Storage.

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.

Preliminary Outcomes of Cervical Cerclage for Shortened Cervix with Decidual Polyp.

The aim of this study was to elucidate the nature of decidual polyp (DP) and to compare DP outcomes treated with cervical cerclage for a shortened cervix with the outcomes of cases treated with cervical cerclage without DP. The medical records of pregnant women who were complicated with cervical polyps were retrospectively reviewed. Cervical cerclage was considered for those cases with a shortened cervical length of under 25 mm and before 25 gestational weeks. We also reviewed pregnant women who had no cervical polyps, and who underwent cervical cerclage during the same study period, and defined them as the control group. A total of 56 pregnant women with cervical polyps were identified. All of the polyps in the 14 cases that had undergone cervical cerclage migrated into the cervical canal. Of the thirty seven cases with cervical polyps that did not necessitate cervical cerclage, eight women delivered preterm and six of these cases were diagnosed as DP. In all of the women studied, polyp migration was observed in 68.6 %. Cervical cerclage was performed significantly earlier in the DP group than in the control group of 46 cases (p < 0.001; 18.4 weeks vs. 21.4 weeks, respectively). Cervical cerclage is effective in DP cases with a shortened cervical length and polypectomy should not be performed during pregnancy because of the risk of miscarriage.

Prevention of intrauterine fetal growth restriction by administrating C1q/TNF-related protein 6, a specific inhibitor of the alternative complement pathway.

PURPOSE: The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development. METHODS: Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed. RESULTS: The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P < 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P < 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P < 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment. CONCLUSIONS: Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.

Non-invasive continuous blood pressure monitoring using the ClearSight system for pregnant women at high risks of post-partum hemorrhage: comparison with invasive blood pressure monitoring during cesarean section.

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.

Altered Transmission of Cardiac Cycles to Ductus Venosus Blood Flow in Fetal Growth Restriction: Why Ductus Venosus Reflects Fetal Circulatory Changes More Precisely.

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.

Transcatheter Arterial Embolization (TAE) Using N-Butyl-2-cyanoacrylate (NBCA) as the First Choice for Postpartum Vulvovaginal Hematoma; Case Series and Reviews of the Literature.

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.

Effects of time-restricted feeding and type of food on fertility competence in female mice.

We assessed the effects of feeding regimen (ad libitum vs. time-restricted food access) and type of food (normal chow (NC: 12% fat) vs. moderately high calorie diet (mHCD: 31% fat)) on fertility competence of female mice. Mice fed mHCD had higher number of oocytes than mice fed NC. On the other hand, when mice were fed NC under time-restricted access to food (NT), the developmental rate to the blastocyst per number of normally fertilized ova was significantly decreased compared to others. The reactive oxygen species (ROS) level in oocytes increased in time-restricted food access and NC group. Transcriptome analysis of whole ovarian tissues from these mice showed a change in the cholesterol metabolism among the four groups. Time-restricted food access decreased serum LDL cholesterol level in both NC and mHCD groups. Moreover, the number of atretic follicles increased in NT mice compared to ad libitum food access mice. The present study shows that mHCD feeding increases the number of ovulated oocytes and that time-restricted feeding of NC impairs the developmental competence of oocytes after fertilization, probably due to the changes in serum cholesterol levels and an increase in the ROS content in oocytes.

Use of Eltrombopag for the First Trimester Pregnancy Complicated with Refractory Idiopathic Thrombocytopenic Purpura: A Case Report and Literature Review.

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.

Effect of Thrombopoietin Receptor Agonist on Pregnant Mice.

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.

Long-term follow up in two cases of pelvic reconstruction using a combined VRAM flap-sacrocolpopexy for severe perineal hernia after abdominoperineal resection.

Perineal hernia is an infrequent complication of abdominoperineal resection (APR) and, currently, there is no consensus as to the optimal operative technique. Surgical repair can be achieved by either cerclage or the use of mesh or autologous tissue, and it has been reported that the recurrence rate after repair using autologous tissue is 33%. We present two post-APR cases of severe perineal hernia with pelvic organ prolapse (POP) which did not improve after repair using mesh. We regenerated the pelvic floor using a vertical rectus abdominis myocutaneous (VRAM) flap and performed a concomitant sacrocolpopexy to fix the POP. Drooping of the perineum and pelvic floor was greatly improved, and the patients have not experienced any recurrence for 6 years. This dual procedure has not been previously mentioned in the literature, and we consider this the first report of its kind.