Placenta Percreta Progression to Resistance Against Uterine Artery Embolization and Penetration Into the Bladder.

A 31-year-old female sought termination of pregnancy due to a fetal body stalk anomaly diagnosed at 18 weeks of gestation. Despite an anterior placenta previa, successful vaginal delivery occurred. However, placental adhesion over a previous cesarean scar occurred, and part of the placenta could not be removed. Immediate postpartum bleeding prompted imaging studies, revealing extravasation from adherent placental remnants. Uterine artery embolization (UAE) provided initial hemostasis, but recurrent bleeding necessitated re-embolization. Although conservative treatment was initially pursued, significant hematuria prompted reevaluation, revealing extensive uterine wall and bladder penetration. Surgical intervention with total hysterectomy and partial bladder resection was performed, leading to the successful recovery of bladder function following surgical repair. While this case achieved a positive outcome, there is a potential for permanent urinary dysfunction if lesions are more extensive. While achieving a conservative cure is ideal, it is essential to assess the timing for opting for surgical intervention.

Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

Twin pregnancy with untyped Ehlers-Danlos syndrome requiring prompt genetic testing: A case report.

Ehlers-Danlos syndrome is a rare genetic disorder that presents with a variety of pathologies depending on the disease type. Among them, vascular Ehlers-Danlos syndrome requires extremely careful management as there have been many reports of fatal perinatal complications such as uterine rupture. Although hypermobile Ehlers-Danlos syndrome is less likely to cause fatal complications, symptoms such as arthralgia, hip dislocation, and depression may be seen throughout pregnancy. We report here a case of twin pregnancy in which Ehlers-Danlos syndrome was first suspected at 19 weeks of gestation. Vascular Ehlers-Danlos syndrome could not be ruled out based on family medical history, making it difficult to determine the perinatal management strategy. Prompt genetic testing did however rule out the vascular type and the patient was diagnosed with hypermobile Ehlers-Danlos syndrome from the clinical symptoms, enabling us to manage the pregnancy safely until 34 weeks of gestation.

Effectiveness of Cross Double McDonald Cerclage for Intractable Bleeding from a Cervical Varix in Pregnant Women.

Cervical varix during pregnancy is a rare condition, and standard management for bleeding from a varix has not been established. We performed cross double cervical cerclage and effectively stopped bleeding. A 41-year-old female had a twin pregnancy. The development of a cervical varix was observed during pregnancy and bleeding from ruptured varix started at 20 weeks of gestation. We performed surgical hemostasis by cervical cerclage. In the first cerclage, we could not stop the bleeding from the varix. For further restriction of blood supply to the cervical varix, we performed a second cerclage in a crossed position on a deeper side of the vagina than the first cerclage. Then the bleeding completely stopped and there was no bleeding until delivery. The "cross double McDonald cerclage" performed in our patient may be a useful modified cerclage method for stopping intractable bleeding from the cervix during pregnancy.

Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection.

Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.

Common iliac artery dissection as a complication of common iliac artery balloon occlusion for placenta percreta: A case report.

A 37-year-old pregnant woman who had undergone three previous cesarean sections was diagnosed as having placenta percreta. We decided to perform cesarean hysterectomy with bilateral common iliac artery balloon occlusion (CIABO). The duration of surgery was 2 h and 2 min and total estimated blood loss was 2600 mL. Surgery was completed without any surgical complications, but the pulse oximeter waveform of the left leg became undetectable during surgery. We immediately performed angiography after closure of laparotomy and found abnormal pooling of contrast media at the left common iliac artery in the region in which the balloon was positioned. We made a diagnosis of left common iliac artery dissection caused by CIABO. We performed emergent revascularization by intravascular stenting. We conclude that CIABO can cause common iliac artery dissection by mechanical stimulation of the inflated balloon. Careful intraoperative evaluation of limb ischemia and preparation of intravascular treatment is needed for a safe procedure.

Pregnancies after vaginal radical trachelectomy (RT) in patients with early invasive uterine cervical cancer: results from a single institute.

BACKGROUND: Radical tracheletomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who desire to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. METHODS: We have performed vaginal RT for 71 patients and have experienced 28 pregnancies in 21 patients. They were followed up carefully according to the follow-up methods we reported previously. Their pregnancy courses and prognoses after the pregnancy were retrospectively reviewed. RESULTS: All the vaginal RTs were performed safely without serious complications, including 6 patients who underwent the operation during pregnancy. The median time to be pregnant after RT was 29.5 months. 13 patients (46%) became pregnant without artificial insemination by husband or assisted reproductive technology. Cesarean section was performed for all of them. The median time of pregnancy was 34 weeks, and emergent cesarean section was performed for 7 pregnancies (25%). The median birth weight was 2156 g. Four patients had trouble with cervical cerclage, and they suffered from sudden premature preterm rupture of the membrane (pPROM) during the second trimester of pregnancy. We underwent transabdominal cerclage (TAC) for all of them and careful management for the prevention of uterine infection was performed. One patient had a recurrence of cancer during pregnancy. CONCLUSIONS: Both the obstetrical prognosis and oncological prognosis after vaginal RT have become favorable for pregnant patients after vaginal RT.

Infant car seat use in Japan after the antepartum distribution of an educational leaflet: A prospective, nonrandomized controlled trial with a questionnaire survey.

Objective: To determine whether an antepartum educational leaflet distributed to parents before infant delivery affected the rate of infant car-seat (ICS) use 1 month after delivery, because to the best of our knowledge, only few reports have evaluated systematic attempts to improve the rate of always ICS use by mothers driving infantsMethods: A multicenter questionnaire survey targeting pregnant Japanese women seeking antenatal care at the outpatient clinics of eight hospitals was designed. Women enrolled during the first half of the study period did not receive leaflets describing ICS safety guidelines (control group). Women enrolled during the latter half of the study period received the leaflet between gestational week 35 and 37 (intervention group). All women were requested to anonymously respond to the questionnaires within 1 month postpartum. The rates of ICS use, position, and direction after delivery were compared between both groups.Results: Of the 3534 women who responded to the questionnaire survey (response rate, 81.9%), 1772 women (50.1%) were assigned to the intervention group and 1762 (49.9%) women to the control group. The rates of ICS attachments (86.8% vs. 82.4% in the intervention and control groups, respectively, p = 0.0003), always ICS use (80.5% vs. 76.2%, respectively, p = 0.0019), ICS placement on the rear seat (78.6% vs. 74.1%, respectively, p = 0.0020), and ICS placement in a rear-facing position (62.2% vs. 56.7%, respectively, p = 0.0008) were significantly higher in the intervention group than those in the control group. The motor vehicle accident (MVA) rates within 1 month postpartum were similar between the intervention and control groups (0.51% vs. 0.57%, respectively, p = 0.8229).Conclusions: Antepartum minimal intervention via the distribution of an educational leaflet recommending ICS safety guidelines was associated with increased rates of ICS attachments, always ICS use, and ICS placement on the rear seat and in rear-facing positions; however, it did not contribute to reduced MVA rates after delivery.

Successful administration of recombinant human antithrombin in a pregnant Japanese woman with hereditary antithrombin deficiency.

OBJECTIVE: Hereditary antithrombin (AT) deficiency increases the risk of venous thromboembolism (VTE) in pregnant woman. We report the first case of administration of recombinant human antithrombin (rhAT) to a pregnant Japanese woman with AT deficiency. CASE REPORT: A 30-year-old woman, gravida 2 para 0, was referred to our hospital because of AT deficiency. Unfractionated heparin was administered from 13 weeks of gestation and rhAT was administered from labor onset. A cesarean section was performed and the patient and her baby were healthy, with no sequelae. CONCLUSION: We concluded that rhAT was effective for preventing VTE during delivery, with no potential infection risks.

Effect of an educational leaflet on the frequency of seat belt use and the rate of motor vehicle accidents during pregnancy in Japan in 2018: a prospective, non-randomised control trial with a questionnaire survey.

OBJECTIVE: To determine whether an educational leaflet had any effect on seat belt use, seat preference and motor vehicle accidents rate during pregnancy in Japan. DESIGN: Prospective, non-randomised control trial with a questionnaire survey. SETTING: Eight obstetric hospitals in Sapporo, Japan. PARTICIPANTS: 2216 pregnant women, of whom 1105 received the leaflet (intervention group) and 1111 did not (control group). INTERVENTIONS: Distribution of an educational leaflet on seat belt use to women in the intervention group. PRIMARY OUTCOME MEASURES: The effect of an educational leaflet on seat belt use, each pregnant woman's seat preference and the women's rates of motor vehicle accidents rate during their pregnancies. To evaluate the effects, the intervention group's responses to the questionnaires were compared with those of the control group. RESULTS: The proportion of subjects who always used seat belts during pregnancy was significantly higher in the intervention group (91.3%) than in the control group (86.7%; p=0.0005). Among all subjects, the percentage of women who preferred the driver's seat was lower during pregnancy (27.0%) than before pregnancy (38.7%), and the percentage of women who preferred the rear seat was higher during pregnancy (28.8%) than before pregnancy (21.0%). These two rates did not differ between two groups. Seventy-one women (3.2%) reported experiencing a motor vehicle accident during pregnancy. The motor vehicle accident rate for the intervention group (3.3%) was similar to that for the control group (3.2%). CONCLUSIONS: An educational seat belt leaflet was effective in raising the rate of consistent seat belt use during pregnancy, but it did not decrease the rate of motor vehicle accidents. The wearing of seat belts should be promoted more extensively among pregnant women to decrease rates of pregnancy-related morbidity and mortality from motor vehicle accidents.

Obstetrical prognosis of patients who underwent vaginal radical trachelectomy during pregnancy.

AIM: Radical trachelectomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who decide to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. Therefore, RT for pregnant patients can be a challenge both for gynecologic oncologists and obstetricians. METHODS: We have performed vaginal RT for five pregnant patients with uterine cervical cancer stage 1B1 according to the method of Dargent et al. The operations were performed between 16 and 26 weeks of pregnancy, and the patients were followed up carefully according to the follow-up methods we reported previously. RESULTS: Vaginal RT was performed for five patients without any troubles. Four of the patients continued their pregnancies until almost 34 weeks or longer under our previously published follow-up schedule. The pregnancy of one patient was terminated at 26 weeks due to recurrence of the cancer. CONCLUSION: Expansion of vaginal RT for pregnant patients with uterine cervical cancer could be a practical option for pregnant patients with early invasive uterine cervical cancer.

Transabdominal cerclage (TAC) for patients with ultra-short uterine cervix after uterine cervix surgery and its impact on pregnancy.

AIM: Patients with an ultra-short uterine cervix as a result of large conization, repeated conization or radical trachelectomy (RT), are at high risk of preterm premature rupture of the membrane, which leads to preterm birth. We have commenced performing transabdominal cerclage (TAC) of the uterine cervix for these patients. In this study, we examined the safety of TAC and its impact on pregnancy. METHODS: We have performed TAC in 11 patients before pregnancy: in six after large cervical operations, such as repeated conization; and in five for difficulties with cervical cerclage after RT. After laparotomy, a Teflon thread was placed in the avascular space between the uterine vessels and the uterine muscle, and tied. The clinical course of the patients after TAC and their pregnancy course were retrospectively reviewed. RESULTS: TAC was performed safely without any complications. The mean operative duration was 53 ± 10 min, and the mean blood loss during the operation was 49 ± 64 mL. Seven women conceived within 2 years after TAC. Their pregnancy courses were favorable. Five of the women underwent scheduled cesarean sections, while two pregnancies are ongoing. CONCLUSIONS: Although there are risks of various complications as a result of the use of non-absorbable thread and the need for two extra laparotomies, TAC can be a safe and useful option for patients who show cervical incompetence after large uterine cervical operations, such as RT or large conization.

Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy.

Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for various diseases including diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from both type 1 and type 2 diabetes models in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN). Then, we developed a novel method to improve abnormalities in BM-MSC using human umbilical cord extracts, namely Wharton's jelly extract supernatant (WJs). WJs is a cocktail of growth factors, extracellular matrixes and exosomes, which ameliorates proliferative capacity, motility, mitochondrial degeneration, endoplasmic reticular functions and exosome secretions in both type 1 and type 2 diabetes-derived BM-MSC (DM-MSC). Exosomes contained in WJs were a key factor for this activation, which exerted similar effects to complete WJs. DM-MSC activated by WJs ameliorated renal injury in both type 1 and type 2 DN. In this study, we developed a novel activating method using WJs to significantly increase the therapeutic effect of BM-MSC, which may allow effective autologous cell transplantation.

Possibility of less radical treatment for patients with early invasive uterine cervical cancer.

AIM: Radical trachelectomy (RT) with lymphadenectomy has become a standard treatment modality for patients with early invasive uterine cervical cancer who hope to preserve fertility. However, pregnancy after RT has high risks of preterm birth. The possibility of more conservative RT and the application of RT for patients with higher clinical stages were studied. METHODS: The medical charts and specimens of 42 patients who underwent RT and 64 patients who underwent radical hysterectomy were retrospectively studied. Tumor size, distance between the margin of the cancer and the internal orifice of the uterus (os), parametrial invasion, lymph node metastasis and prognoses were investigated. RESULTS: The average distances between the inner margin of the cancer and the internal os were 37 mm, 29 mm, 18.7 mm and 14 mm for patients with stage 1 A2, 1B1 (≤ 2 cm), 1B1 (> 2 cm) and 1B2, respectively. When amputation was performed 10 mm below the internal os, all 10 patients with 1 A2, 57 with 1B1 (≤ 2 cm), 19 with 1B1 (> 2 cm), and one with 1B2 had a cancer-free margin > 10 mm. Patients with stage 1 A2 had a cancer-free margin > 10 mm even if we amputated the cervix 20 mm below the internal os. Parametrial invasion was detected in two patients with stage 1B1. CONCLUSIONS: A simple trachelectomy 20 mm below the internal os with pelvic lymphadenectomy might be possible for stage 1 A2 patients. The present method is best for stage 1B1 patients (≤ 2 cm). RT for stage 1B1 (>2 cm) or higher stages should be contraindicated.

Obstetrical prognosis of patients with cervical intraepithelial neoplasia (CIN) after "coin-shaped" conization.

PURPOSE: Uterine cervical conization is related to adverse pregnancy outcomes in subsequent pregnancies. To deal with this problem, we started conservative coin-shaped conization for reproductive-aged patients with cervical intraepithelial neoplasia (CIN). Here we report both the obstetrical and oncological impacts of this operation in comparison with the standard cone-shaped resection. METHODS: A total of 401 women 44 years old or younger were treated in our hospital by CO2 laser conization between 2003 and 2012, and subsequently 50 patients became pregnant. The patients were divided into two groups, a standard cone-shaped conization group (until 2008) and a shallow coin-shaped conization group (beginning in 2008). The pregnancy courses and oncological prognoses of these two groups were studied. RESULTS: Cone height reduction of about 3 mm was done. However, there were no significant differences between the two groups with regard to the occurrence of oncological complications. In the standard conization group, 18 of the 25 patients delivered at term. In the coin-shaped conization group, 20 of the 25 patients delivered at term. There were no significant differences between the two groups with regard to the occurrence of various obstetrical complications. However, the reduction rate of cervical length over the pregnancy was smaller in the coin-shaped group and the number of patients with a short cervix length of 2 cm or less was smaller in the coin-shaped group. CONCLUSIONS: Although conservative coin-shaped conization did not markedly improve the obstetrical prognosis, this operative procedure improved the reduction rate of uterine cervical length over the pregnancy without any increase in oncological complications.

Preservation of fertility and subsequent childbirth after methotrexate treatment of placenta percreta: a case report.

INTRODUCTION: Placenta percreta is associated with maternal morbidity and mortality. A hysterectomy is often needed to control the bleeding in such cases. However, it has been advocated that placenta percreta be managed conservatively to avoid massive pelvic bleeding and to preserve the patient's fertility. Here, we present a case of placenta percreta diagnosed by magnetic resonance imaging, and treated with systemic administration of methotrexate. CASE PRESENTATION: A 27-year-old nulliparous Japanese woman at 39 gestational weeks had an uncomplicated vaginal delivery of a 3244-g infant. However, her placenta was not delivered, and we could not remove it manually. Contrast-enhanced magnetic resonance imaging indicated deep myometrial invasion by placental tissue and the whole placenta was strongly enhanced. Seven days post-partum, her serum human chorionic gonadotropin level was 12,656IU/L. Our patient hoped to preserve her uterus for a future pregnancy. She therefore received 13 courses of methotrexate (50mg/week, intravenous injection). Her serum human chorionic gonadotropin level was undetectable 97 days after the first methotrexate injection. At 117 days post-partum, she had a labor-like pain every three minutes and delivered the placenta. Our patient regained normal menses and at follow-up remained in good health. Two years later, she delivered a healthy daughter. CONCLUSION: We should try to detect placenta percreta in high-risk patients by any means. For low-risk patients, we should give a diagnosis swiftly and control any intrauterine infection and massive bleeding.

Successful delivery after transabdominal cerclage of uterine cervix for cervical incompetence after radical trachelectomy.

Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and complications such as preterm premature rupture of the membrane and chorioamnionitis. Placing a cervical cerclage at the time of RT plays an important role in preventing such obstetrical complications. In patients who have trouble with the cervical cerclage, miscarriage during the second trimester seems to be inevitable. We have therefore started preconception transabdominal cerclage (TAC) for these patients. A 36-year-old Japanese woman who had a history of miscarriage due to trouble with the nylon thread used for cerclage, successfully delivered after TAC. TAC is a useful treatment modality to prevent miscarriage for patients who have trouble with cerclage after RT.