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Aim: We aimed to investigate the associations of endometriosis and adenomyosis with pregnancy complications by using a large‐scale Japanese database. Methods: We retrospectively analyzed 145 590 singleton pregnancies from the Japan Perinatal Registry Network Database. Pregnant women registered as having endometriosis or adenomyosis were designated as the case group (EA), whereas the control group (non‐EA) was selected using propensity‐score matching adjusted for variables such as age, parity, BMI, smoking history, and the use of assisted reproductive technology. The main outcomes included placental malposition, preterm birth, and hypertensive disorders of pregnancy (HDP). Results: In total, 1203 patients from both the EA and non‐EA groups were matched and evaluated. The EA group showed significantly higher rates of placenta previa (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.84–4.92), low‐lying placenta (OR, 2.02; 95% CI, 1.06–3.86), and preterm birth (OR, 1.44; 95% CI, 1.13–1.84) than the non‐EA group. However, no significant difference was observed in the incidence of HDP (OR, 1.22; 95% CI, 0.90–1.66). Conclusion: The use of propensity‐score matching to analyze a nationwide perinatal database in Japan clarified that EA was associated with increased pregnancy complications, specifically placental malposition, including placenta previa and low‐lying placenta, and preterm birth, but not with HDP. [ABSTRACT FROM AUTHOR]

Aim: Cryoprecipitate (CRYO) is a concentrated preparation of coagulation factors formulated from fresh frozen plasma (FFP), which can replenish coagulation factors rapidly. Preeclampsia (PE) is frequently associated with postpartum hemorrhage (PPH), and the rapid replenishment of coagulation factors is vital in the management. We conducted a retrospective cohort study to determine the efficacy of administering CRYO irrespective of fibrinogen levels in patients with PE who experienced severe PPH. Methods: Patients with PPH accompanied by PE and those who required red blood cell (RBC) transfusion were included. Cases were divided into two groups: those treated with CRYO (N = 16) and those not treated with CRYO (N = 10). The total transfusion volume, blood loss before and after transfusion initiation, duration of hospitalization, presence of pulmonary edema, and performance of either interventional radiology or hysterectomy were compared. Results: The median fibrinogen levels before transfusion were 2.24 and 2.34 g/L in the CRYO group and the not using group, respectively. Although blood loss before transfusion was comparable between the two groups, blood loss after transfusion was significantly less in the CRYO group (median: 520 vs. 2352 mL, p = 0.015), as well as the total blood loss (median: 2285 vs. 3825 mL, p = 0.005) and total transfusion volume (median: RBC 6 vs. 16 U, p = 0.01, FFP 10 vs. 20 U, p = 0.017). Conclusion: Prompt replenishment of coagulation factors using CRYO to patients with PE who experience severe PPH could decrease further bleeding. [ABSTRACT FROM AUTHOR]

Imaging and histological changes occurring in adenomyosis due to pregnancy are unclear. A 38‐year‐old nulliparous woman presented with dysmenorrhea and infertility. Pelvic magnetic resonance imaging (MRI) showed diffuse‐type adenomyosis. Following pregnancy by in vitro fertilization, she was hospitalized at 23 weeks of gestation due to fetal growth restriction and subsequently diagnosed with preeclampsia. A second MRI performed due to an elevated inflammatory response at 31 weeks of gestation detected no obvious degenerative findings. An emergency cesarean section was performed at 33 weeks of gestation because of nonreassuring fetal status. On postpartum day 2, she showed uterine tenderness with a dramatically elevated inflammatory response. A third MRI showed cyst‐like degenerations with hemorrhagic changes without abscess. By postpartum day 7, she was quickly relieved and discharged from the hospital. A fourth MRI at postpartum month 4 confirmed the disappearance of degenerations. This is the first report of imaging findings of early postpartum degeneration of adenomyosis. [ABSTRACT FROM AUTHOR]

Uterine fibroids are known to degenerate during pregnancy, but it is unknown if similar pathologic condition occurs in adenomyosis. A 38‐year‐old para 1 woman exhibited uterine tenderness and a markedly elevated inflammatory response at 22 weeks of gestation. Based on magnetic resonance imaging (MRI) findings indicative of hemorrhagic components in an adenomyosis lesion, we judged these features resulted from degeneration of adenomyosis after excluding the possibility of underlying infection by amniocentesis. Although these symptoms improved with conservative management, nonreassuring fetal status prompted an emergency cesarean section at 27 weeks of gestation. MRI performed 4 months postpartum revealed the degeneration had completely disappeared. The present case confirms the presence of a pathologic condition—transient degeneration in adenomyosis—which is triggered by pregnancy. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the impact of fetal growth restriction (FGR) as a diagnostic criterion for preeclampsia (PE) on the severity of maternal preeclamptic features by comparing it with other diagnostic criteria for PE, maternal organ dysfunction. Methods: We performed a retrospective cohort study of singleton pregnancies. Based on the status at diagnosis, PE cases preceded by FGR without maternal organ dysfunction (Group F; n = 28) and those preceded by maternal organ dysfunction without FGR (Group M; n = 87) were analyzed. Results: Group F had an earlier PE diagnosis (32.5 ± 4.9 vs. 36.7 ± 3.5 weeks, p < 0.01) and delivery (33.7 ± 4.5 vs. 37.5 ± 3.1 weeks, p < 0.01) than Group M. No significant differences in maternal morbidities were observed between the groups, including severe hypertension (75.0 vs. 60.0%), need for intravenous antihypertensives (42.9 vs. 48.3%) or magnesium sulfate (60.7 vs. 54.5%), or a composite of major maternal complications (17.9 vs. 21.8%). When limited to early‐onset PE diagnosed before 34 weeks of gestation (17 and 17 cases in Group F and M, respectively), the frequencies of maternal morbidities (severe hypertension: 70.6 vs. 52.9%, intravenous antihypertensives: 35.3 vs. 35.3%, magnesium sulfate: 58.8 vs. 47.1%, major complications: 29.4 vs. 23.5%) and the duration from diagnosis until delivery (11.2 ± 14.7 vs. 16.5 ± 21.7 days) were comparable between two groups. Conclusions: Our results suggest that the presence of FGR on PE diagnosis is associated with the development of severe maternal symptoms as much as that of maternal organ dysfunction at diagnosis, and it may be reasonable to include FGR in PE diagnostic criteria. [ABSTRACT FROM AUTHOR]

Preeclampsia is characterized by the emergence of hypertension and proteinuria after 20 weeks of pregnancy, and it threatens both maternal and fetal lives if it proceeds unabated. Despite numerous studies, thus far the only fundamental therapy for preeclampsia is termination of pregnancy, leading to preterm birth. Furthermore, preeclamptic women are reported to be at risk for cardiovascular diseases for 10 years after delivery. Therefore, preventative and therapeutic strategies for preeclampsia are required. Recently, statins have been reported to improve the regeneration of vascular endothelium, and pravastatin has attracted attention as a potential preventative or therapeutic candidate for preeclampsia. Pravastatin has been demonstrated to have preventative effects in preeclampsia model mice, and a large volume of human data from pregnant women taking statins supports the safety of these drugs. Moreover, small clinical trials have reported that pravastatin has strong preventative or therapeutic effects on preeclampsia and it has the potential to improve the prognosis of pregnant women, fetuses and neonates affected by this condition. [ABSTRACT FROM AUTHOR]

HELLP syndrome is sometimes followed by massive bleeding, leading to DIC. In cases of intra‐abdominal compartment syndrome due to massive intra‐abdominal bleeding after cesarean section, if preeclampsia and partial HELLP syndrome persist, hematoma removal helps in the recovery from preeclampsia and partial HELLP syndrome. [ABSTRACT FROM AUTHOR]

Aim: This study aimed at evaluating the additional anti‐tumor effects of exogenous rVEGFR1 (sFlt1) on conventional chemotherapy in ovarian cancer cell lines. Methods: We utilized cells from two ovarian cancer cell lines, SKOV3 and HeyA8, and treated them with a combination of rVEGFR1 (sFlt1) and carboplatin as well as rVEGFR1 (sFlt1) alone. First, we evaluated cell survival after treatment by using cell counting and MTS assays. Next, we performed Ki67 staining for evaluating the inhibitory effects of the treatment on cell proliferation, and a lactate dehydrogenase (LDH) assay for evaluating cytotoxicity. Finally, to determine whether MAP kinase signaling is involved in this process, we performed western blot analysis of extracellular signal‐regulated kinase (ERK), phospho‐ERK, c‐jun n‐terminal kinase (JNK) and phospho‐JNK. Results: The cytotoxic and growth‐restriction effects were more pronounced in the group co‐administered with rVEGFR1 (sFlt1) and carboplatin than in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. Quantitative analysis of Ki67‐positive cells also showed a decreased proportion of Ki67‐positive cells in SKOV3 cells treated with a combination of exogeneous rVEGFR1 (sFlt1) and carboplatin compared to that in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. In the LDH assay, we also found significantly enhanced cell toxicity from the combination therapy. Finally, western blotting analysis showed that the MAPK signaling pathway was not affected by sFlt1 treatment. Conclusion: This study confirmed the additive effects of rVEGFR1 (sFlt1) combined with conventional chemotherapy for ovarian cancer growth in in vitro assays, thus suggesting the combination of rVEGFR1 (sFlt1) and carboplatin as a potential novel therapeutic option for ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Ovarian tissue cryopreservation before cancer treatment is the only option to preserve fertility under some circumstances. However, tissue ischemia after transplantation while awaiting angiogenesis induces dysfunctional folliculogenesis and reduces ovarian reserve and is one of the disadvantages of frozen‐thawed ovarian tissue transplantation. Basic fibroblast growth factor (bFGF) is a major regulator of angiogenesis. However, bFGF rapidly loses biological activity when its free form is injected in vivo. This study investigated whether administration of active bFGF helps establish a nurturing environment for follicular survival. Methods: A sheet form of a sustained release drug delivery system for bFGF was developed using biodegradable acidic gelatin hydrogel (bFGF sheet). The bFGF sheets or phosphate‐buffered saline sheets, as a negative control, were transplanted with frozen‐thawed human ovarian tissues subcutaneously into the backs of severe combined immunodeficient mice. Neovascularization, cell proliferation, fibrosis and follicular survival of ovarian grafts were analyzed at 6 weeks after xenografting. Results: The bFGF sheets were optimized to release bFGF for at least 10 days. The transplantation of bFGF sheets with frozen‐thawed ovarian tissues significantly increased human and mouse CD31‐positive areas and stromal and endothelial cell proliferations. The administration of bFGF also significantly decreased the percentage of the fibrotic area in the graft, resulting in a significant increase in primordial and primary follicular density. Conclusion: Local administration of a sustained release of biologically active bFGF induced neovascularization in frozen‐thawed ovarian tissue grafts, which could establish the nurturing environment required for follicular survival in heterotopic xenografts. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: During the implantation period, the uterus goes through many complex, orchestrated changes, including alterations of the glycocalyx that are due to sialylation, sulfation, and fucosylation. A previous mouse study showed that the in vivo intrauterine oxidation‐reduction potential (ORP) aided in determining the alterations in the uterine endometrium that are suitable for implantation and for evaluating prospective uterine receptivity, while the in vivo intrauterine pH did not. It was assessed if the in vivo intrauterine ORP could be a useful parameter to predict pregnancy in women. Methods: A prospective cohort study was conducted for patients who had received a frozen‐thawed single embryo transfer in a programmed, hormonally controlled cycle. The in vivo intrauterine ORP was measured 3 times during the treatment cycle, at cycle days 9‐10, 1 day before progesterone administration and immediately before the embryo transfer. Results: The amount of in vivo intrauterine ORP at 9‐10 days after the start of menstrual bleeding was significantly lower in the pregnant group than in the non‐pregnant group. A receiver‐operator characteristic curve analysis of the intrauterine ORP as a predictor of non‐conception showed an area under the curve of 0.80. Conclusion: The in vivo intrauterine ORP could be a useful parameter to predict pregnancy for the frozen‐thawed embryo transfer treatment cycle. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. Methods: Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a ‘postlaparoscopic resection of the rudimentary horn’ group (study group) and an ‘other uterine anomalies’ (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. Results: Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (<10th percentile) (0% vs 24.2%; P = .31) and HDP rate (0.0% vs 3.0%; P = 1.0). Three of seven cases with postlaparoscopic resection of the rudimentary horn were able to deliver vaginally without complications. Conclusion: Our study shows that the obstetric outcome observed in the study group was similar to that observed in the control group. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to report the pregnancy outcomes of women who received different doses of corticosteroid supplementation during labor and delivery. Methods We conducted a retrospective review of 102 pregnant women who received oral corticosteroid therapy, delivered at Osaka University Hospital, and were administered intravenous corticosteroid supplementation during labor and delivery. From January 2008 to May 2012, 47 women were administered a high dose of corticosteroids (HD group). From June 2012 to December 2016, 55 women were given a low dose of corticosteroids (LD group). Results There were no significant differences in the patient characteristics between the two groups. The most frequent disease was systemic lupus erythematosus (30/102; 29.4%). Most women used prednisolone for more than 1 year (91/102; 89.2%) and at a dose of more than 5 mg/day (88/102; 86.3%). The total intravenous dose of hydrocortisone during labor and delivery ± standard deviation was 233.5 ± 129.4 mg (HD group) and 143.4 ± 38.1 mg (LD group), exhibiting a significantly larger dose in the HD group. No patients suffered an adrenal deficiency and there were no significant differences in the hemodynamics. There were three cases of puerperal endometritis, two patients with hyperglycemia, and one wound infection in the HD group, whereas one case of puerperal endometritis in the LD group. There were no significant differences in the neonatal outcomes. Conclusion Pregnancy outcomes did not differ between the high and low doses of corticosteroid supplementation during labor and delivery. [ABSTRACT FROM AUTHOR]

Key Clinical Message The incidence of cesarean section (c-section) has increased worldwide. Because the major risk factor for uterine scar dehiscence (USD) is a previous c-section, the rate of this complication has also increased. Its clinical significance and management strategies are unclear. Here, we discuss USD particularly pertaining to its surgical treatment. [ABSTRACT FROM AUTHOR]

Placenta percreta is a rare condition that presents a risk of massive intraoperative hemorrhage. To decrease maternal morbidity in such cases, conservative management was recently adopted as an option. Nevertheless, severe morbidity occurs in 42% of cases. In addition, the clinical course of conservative management remains unclear. We encountered a case of placenta percreta that was successfully treated by conservative management without complications or other clinical interventions. Serial magnetic resonance imaging (MRI) was performed to investigate the natural course of conservative management of placenta percreta. MRI on postoperative day (POD) 99 showed a decrease in placental size without gadolinium enhancement. MRI on POD 162 showed that the residual placenta was approximately 4 cm in size without gadolinium enhancement. On POD 265, the placenta had almost disappeared. This is the first series of MRI of conservative management of placenta percreta without clinical interventions. We present our case and a literature review. [ABSTRACT FROM AUTHOR]

Uterine cervical varix is rare, and its clinical course is poorly understood. Therefore, we present a case report of cervical varix complicating placenta previa before describing our findings in the context of an electronic database search of relevant reports. In the case report, we describe the clinical course and imaging results of a 35-year-old woman who was diagnosed with cervical varix complicated by placenta previa. Investigation by magnetic resonance imaging, serial ultrasonography, and speculum confirmed the diagnosis, and a healthy baby was successfully delivered at 36 weeks of gestation by cesarean section. An electronic search identified nine previous cases of cervical varix complicated by placenta previa in the literature. Clinicians should be aware of cervical varices when managing placenta previa to avoid iatrogenic rupture or misdiagnosis of placenta accreta by magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Key Clinical Message Hardly any report exists on the influence of hysteroscopic myomectomy on subsequent pregnancy. Placenta accreta is most often associated with placenta previa in women with multiple prior cesarean sections. We report the first case of placenta accreta without placenta previa during the first pregnancy subsequent to hysteroscopic myomectomy. [ABSTRACT FROM AUTHOR]

Key Clinical Message Placenta percreta (with bladder invasion) is a rare obstetric condition with the risk of massive intraoperative hemorrhage. In these cases, the combination of a transverse uterine fundal incision and retrograde cesarean hysterectomy could be useful to minimize maternal hemorrhage and avoid severe bladder injury. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to determine whether uterine blood flow is an effective parameter to anticipate uterine receptivity. Material and Methods The local uterine blood flow was measured in the endometrium and on the outside of the uterus in mice during the early stage of pregnancy and an implantation failure mouse model using transient and local suppression of signal transducer and activator of transcription-3 activity during implantation. Results The local uterine blood flow was dramatically increased after mating and was decreased towards the time of implantation. The local uterine blood flow at 2.5 days post-coitus in signal transducer and activator of transcription-3 decoy transferred mice was significantly higher than in control mice. However, the range of individual values was too wide to find a cut-off point. Conclusions It is necessary to decrease local uterine blood flow after ovulation to prepare the opening implantation window. The optimal local uterine blood flow is regulated by time events during pregnancy. The range of individual values of uterine blood flow is wide using a laser Doppler blood flow meter. This parameter itself may not be an appropriate parameter to evaluate the prospect of uterine receptivity. [ABSTRACT FROM AUTHOR]

Problem The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR-deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized. Methods of study We tested the gene expression profile of OTRKO mice using suppressive subtractive hybridization, and focused on the calcineurin/nuclear factor of activated T cells (NFAT) pathway. We examined the expression and localization of this pathway in mouse parturition. Results Calcineurin and NFATc1 were detected in the decidua of pregnant uteri at term using immunohistochemistry (IHC). We identified higher activation levels of NFATc1 in wild type (WT) than in OTRKO mice and increased calcineurin A and NFATc1 mRNA levels during pregnancy. Moreover, injection of FK506, the inhibitor of this pathway, prolonged the delivery of the first pup. Conclusion Our findings suggested that the calcineurin/NFAT pathway might play a substantial role in initiation of labor. [ABSTRACT FROM AUTHOR]

Background: The uterus is an organ that is directly accessible via the transvaginal route, whereas the drug delivery system and the gene delivery system (GDS) for the uterus are very limited, even in animal models. In the present study, we optimized a bionanocapsule (BNC) comprising a hepatitis B virus envelope L‐protein particle, for which a structurally similar particle has been used as an immunogen of a conventional HB vaccine worldwide for more than 30 years, as a local uterine GDS using a mouse model. Methods: To display various antibodies for re‐targeting to different cells other than hepatic cells, the pre‐S1 region of BNC was replaced with a tandem form of the protein A‐derived immunoglobulin G Fc‐interacting region (Z domain, ZZ‐BNC). To induce strong cell adhesion after local administration into the uterine cavity, ZZ‐BNC was modified with a transactivator of transcription (TAT) peptide. Results: Gene transfer using TAT‐modified ZZ‐BNC is approximately 5000‐ or 18‐fold more efficient than the introduction of the same dose of naked DNAs or the use of the cationic liposomes, respectively. TAT‐modified ZZ‐BNC was rapidly eliminated from the uterus and had no effect on the pregnancy rate, litter size or fetal growth. Conclusions: TAT‐modified ZZ‐BNC could be a useful GDS for uterine endometrial therapy via local uterine injection. [ABSTRACT FROM AUTHOR]

Problem: Recent advances in lipid research have revealed that impairments in lipid mediator signaling can be involved in the pathoetiology of a variety of diseases. We previously reported aberrant expression of autotaxin, a key enzyme for lysophosphatidic acid (LPA) production, in placentas from women with preeclampsia. The present study aimed to further explore the involvement of LPA signaling in the pathoetiology of preeclampsia. Method of study: Term placentas were obtained from deliveries after uncomplicated pregnancy (n = 18) and those complicated by preeclampsia (n = 24). First‐trimester placental tissues were collected after elective terminations of pregnancy (n = 20). Placental expression of the six identified LPARs (LPAR1‐6) was analyzed at protein and mRNA levels. Results: In normal pregnancy, the mRNA expression levels of all LPARs except LPAR4 were significantly higher in term. Levels of mRNA encoding LPAR2‐5 were significantly increased in preeclampsia placentas compared with those in the normal term placentas. Using Western immunoblotting, only LPAR3 was noted to be increased at the protein level in placentas from preeclamptic pregnancies. This was validated by immunohistochemistry. Conclusion: In summary, the placental expression of LPARs, particularly LPAR3, is enhanced in preeclampsia, suggesting that disturbances in placental LPA signaling may be involved in the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder. Female carriers can manifest symptoms during pregnancy, complicating diagnosis and genetic counseling before conception. This is the first report of a DMD symptomatic carrier who was managed continuously from preconception through pregnancy for symptoms recognized before conception. A 31-year-old primipara woman was incidentally noted to have premature ventricular contractions, heart failure, and elevated creatine kinase levels 2 years before pregnancy. Genetic testing confirmed that the patient was a symptomatic carrier of DMD. She had no family history of muscular or cardiac disease, suggesting a de novo variant. She received genetic counseling and planned amniocentesis during pregnancy as prenatal diagnosis. After treatment with bisoprolol and flecainide, her cardiac function improved, and natural conception was achieved. Amniocentesis performed at 16 weeks of gestation indicated a 46, XX karyotype, leading to the decision to continue the pregnancy. From week 16 to 21, the fetus exhibited bradycardia due to blocked premature atrial contraction, which later improved, although the atrioventricular interval was prolonged. The mother delivered vaginally without any complications, and the infant's atrioventricular interval normalized. Preconceptional diagnosis and treatment for DMD carrier status are crucial for shared decision-making and to achieve favorable perinatal outcomes., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)