Archives of Gynecology and Obstetrics

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Objective To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I² > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). Results The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). Conclusions Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.
Study search and selection flow chart in the systematic review of progesterone supplementation for luteal phase support
Study quality assessment in the systematic review of progesterone supplementation for luteal phase support (summarized using individual study quality data in Table 2)
Objective To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer. Design Systematic review. Patients Women undergoing frozen embryo transfer (FET). Interventions We conducted an extensive database search of Medline (PubMed), Embase, Web of Science, and Cochrane Trials Register using relevant keywords and their combinations to find randomized controlled trials (RCTs) comparing the routes (i.e., oral, vaginal, intramuscular) of progesterone administration for luteal phase support (LPS) in artificial FET. Main outcome measures Clinical pregnancy, live birth, miscarriage. Results Four RCTs with 3245 participants undergoing artificial endometrial preparation (EP) cycles during FET were found to be eligible. Four trials compared vaginal progesterone with intramuscular progesterone and two trials compared vaginal progesterone with oral progesterone. One study favored of vaginal versus oral progesterone for clinical pregnancy rates (RR 0.45, 95% CI 0.22–0.92) and other study favored intramuscular versus vaginal progesterone for clinical pregnancy rates (RR 1.46, 95% CI 1.21–1.76) and live birth rates (RR 1.62, 95% CI 1.28–2.05). Tabulation of overall evidence strength assessment showed low-quality evidence on the basis that for each outcome-comparison pair, there were deficiencies in either directness of outcome measurement or study quality. Conclusion There was little consensus and evidence was heterogeneous on the optimal route of administration of progesterone for LPS during FET in artificial EP cycles. This warrants more trials, indirect comparisons, and network meta-analyses. PROPERO No CRD42021251017.
Flowchart of distribution of the study population
Indications for invasive testing and distribution of abnormal results
Introduction Several congenital abnormalities present late in pregnancy necessitating invasive testing to rule out genetic/infectious causes at late gestation. Not many studies have described the indications/safety of a late gestation amniocentesis. Methods All records of amniocentesis performed beyond 24 weeks were reviewed and evaluated for indications, positive yield and complications. Results About 187 women had an amniocentesis after 24 weeks for various indications with CNS abnormalities being the commonest. The total yield of positive findings was 14.60% (22/150; excluding 2 VOUS). CNS, multiple system involvement and skeletal system anormalities yielded maximum results. About 32.05% abnormalities could have potentially been detected at the time of a routine anomaly scan. Amongst all the deliveries, 2.1% delivered spontaneously within a week of the procedure and about 5.4% delivered spontaneously within a month of the procedure. Conclusion The study emphasises the need for additional accreditation (FMF, ISUOG) of sonographers to ensure the detection of anomalies at the routine 18–20 weeks scan. Inspite of a normal mid-trimester scan, central nervous system and gastrointestinal abnormalities presented more commonly after 24 weeks. The high positive yield in our study highlights the importance of testing even in late pregnancy beyond the legal age of termination. The test could clearly stratify the pregnancies with a poor outcome whilst reassuring the others. The procedure itself did not lead to a neonatal death due to prematurity.
This detail of a dissection protocol documents a false cause of death. Above: detail of the upper right hand corner of dissection protocol no. 26. “letzte Blutung” translates as “last bleeding”. Below: transliteration in Deutscher Einheits-Kurzschrift (German Standard Shorthand) available at for “sest mör derin [Selbstmörderin]”, i.e., suicidal woman, allowing for an individual style of shorthand that Stieve may have acquired over the years
Purpose Hermann Stieve (1886–1952), director of the Berlin Anatomical Institute from 1935, benefited from the rise of execution numbers during the “Third Reich”. He used organs and tissues from executed women for his histological research on the reproductive organs and investigated the influence of “nervous agitation” on the cyclical changes of endometrium and ovary. It is still controversial how he was able to acquire intimate data on the executed women and it was therefore suggested that some of his data may have been “invented”. Methods Newly emerged dissection protocols and histological drawings from Stieve’s research, together with archived court records, enable a more detailed analysis of Stieve’s published data. Results We extracted 304 case descriptions from Stieve’s publications. Of these, 88 could be linked with 33 identifiable women and related historical records. Nearly all reported causes of death and/or verdicts of executed women were false. Reported clinical data, particularly the day of the menstrual cycle and uterine bleeding shortly before death, are more difficult to verify. We found non-standardised documentation and possible confusions of cases, which may in part be attributable to war effects. Conclusion Stieve actively concealed the fate of the executed women, mostly by inventing imaginary stories. This followed a request by the German and Soviet authorities after 1945 not to publish results from cases of political victims, but only from “dangerous criminals”. Scientifically relevant clinical data were not always reported correctly, but are not necessarily fraudulent as different interpretations of this finding can be suggested.
Purpose In Gonadotropin releasing hormone(GnRH) agonist IVF, after administration of human chorionic gonadotropin(HCG) triggering, there is a risk of ovarian hyperstimulation syndrome(OHSS). Few methods exist to prevent OHSS in these cases. Therefore, we investigated the use of a GnRH antagonist to decrease the risk of OHSS, due to its ability to decrease VEGF production and function. Method A retrospective cohort study of 171-IVF patients at risk for developing OHSS after a GnRH agonist cycle with HCG trigger was performed from 2011 to 2019. The patient population consisted of women with an unexpected exuberant response to stimulation based on ovarian reserve testing and were triggered with hCG. Women were converted to a freeze-all cycle and received either cabergoline 0.5 mg orally alone for 7 days from the collection(Group 1, n = 123) or received cabergoline 0.5 mg orally and ganirelix, 250 mcg SC for 7–10 days(Group 2, n = 48). Results Group 1 had more cases of moderate and severe OHSS than group 2-(25% vs. 10% p = 0.03, and 52% vs. 25% p = 0.001 respectively). Group 1 reported more abdominal discomfort and bloating than group 2(91% vs. 65% p < 0.001) and the presence of free fluid was more frequent in group 1 than group 2(74% vs. 35% p < 0.001). Hemoconcentration and electrolyte disturbances were less severe in group 2 than in group 1 (p < 0.001 all cases). Conclusion In patients at high risk for developing OHSS after hCG trigger in a GnRH agonist cycle, the addition of GnRH antagonists in the luteal phase may reduce the risk of developing moderate and severe OHSS. The GnRH antagonist likely leads to more rapid luteolysis and down regulation of VEGF production and receptor response, thereby decreasing the hallmark increased vascular permeability.
Flowchart of the study participants
Receiver operating characteristic (ROC) curve of the final model
Purpose An emergency caesarean section (CS) has more complications than a planned CS. The arrest of labour is a major indication for an emergency CS. This study aimed to develop a prediction model for the arrest of labour to be used in regular check-ups at 36 or 37 gestational weeks for primiparas. Methods This was a retrospective cohort study conducted at a single institution in Japan using data from January 2007 to December 2013. Primiparas attending regular check-ups during 36 or 37 gestational weeks, with live single foetuses in a cephalic presentation were included. The outcome was the incidence of labour arrest. Candidate predictors included 25 maternal and foetal findings. We developed a prediction model using logistic regression analysis with stepwise selection. A score was assigned to each predictor of the final model based on their respective β coefficients. Results A total of 739 women were included in the analysis. Arrest of labour was diagnosed in 47 women (6.4%), and all of them delivered by emergency CS. The predictors in the final model were a Bishop score ≤ 1, maternal height ≤ 154 cm, foetal biparietal diameter ≥ 91 mm, pre-pregnancy weight ≥ 54 kg, maternal haemoglobin concentration ≥ 11.0 g/dl, and amniotic fluid index ≥ 13. The area under the receiver operating characteristic curve was 0.783. Conclusion We have developed the first model to predict arrested labour before its onset. Although this model requires validation using external samples, it will help clinicians and pregnant women to control gestational conditions and make decisions regarding planned CS.
Purpose Regional anesthesia (RA) is considered as a “minimally invasive technique” to achieve anesthesia. To assess the feasibility and the perioperative outcomes of laparoscopic hysterectomy in regional anesthesia from the point of view of the surgeon, anesthesiologist and patient. Methods A retrospective search was performed to identify patients who underwent laparoscopic hysterectomy under RA from April 2020 to September 2021. Five patients affected by benign gynecological disease (atypical endometrial hyperplasia or uterine leiomyomas) were included. Results The postoperative pain, nausea, and vomiting (PONV) and the antiemetic/analgesic intake were evaluated. Postoperative surgical and anesthesiological variables were recorded. Duration of surgery was 84 ± 4.18 and no conversion to GA was required. According to VAS score, the postoperative pain during the whole observation time was less than 4 (median). A faster resumption of bowel motility (≤ 9 h) and patient’s mobilization (≤ 4 h) were observed as well as a low incidence of post-operative nausea and vomit. Early discharge and greater patient’s satisfaction were recorded. Intraoperatively pain score was assessed on Likert scale during all the stages of laparoscopy in RA, with only 2 patients complaining scarce pain (= 2) at pneumoperitoneum. Conclusion RA showed to have a great impact on surgical stress and to guarantee a quicker recovery without compromising surgical results. RA technique could be a viable option for patients undergoing laparoscopic hysterectomy.
Flow chart of the patients’ selection: patients were divided into 3 groups according to their age. In a second analysis, we excluded patients with a family or personal Breast cancer (BC) history
Introduction Breast cancer (BC) screening has been associated with reduced mortality and morbidity. This study compares tumor characteristics and treatment morbidity in screened versus diagnosed women. Materials and methods This retrospective study, conducted between 2010 and 2013, included 666 BC screened or diagnosed patients. We compared patients and tumors characteristics and received treatments. We also analyzed the results after excluding patients at risk of BC and conducted a multivariate analysis to assess odds ratios (OR). Results Screened women had smaller tumors (16,5 vs 22,6 mm, p < 0.001), of lower grade (p < 0.001) with a lower proliferation index (PI) (p < 0.001) than diagnosed women. Screened women were more frequently treated using conservative surgery (82.8% vs 59.7%, p < 0.001), needed less often axillary dissection (15.1% vs 35.4%, p < 0.001) and less often chemotherapy (20.8% vs 48.3% p < 0.001) than diagnosed women. In the multivariate analysis after adjustment for age and BC history, diagnosed women had increased (OR: 4.79, 95% IC: 3.19–7,18) risk to be administered chemotherapy and to undergo axillary dissection (OR: 4.18, 95% IC: 1.56–11.17) than screened women. Conclusion Patients should be informed about the benefits in terms of morbidity that screening confers to them.
Purpose An increasing incidence of breast cancer can be observed worldwide. Since a delay of therapy can have a negative impact on prognosis, timely cancer care is an important quality indicator. By receiving treatment at a certified breast cancer center, the patient has the best chance of treatment in accordance with guidelines and the best prognosis. The identification of risk factors for a delay of therapy is of central importance and should be the basis for a continuous optimization of treatment at breast cancer centers. Methods This retrospective study included women with breast cancer (primary diagnosis, relapse, or secondary malignancy) at the University Hospital Würzburg in 2019 and 2020. Data were retrieved from patients’ records. Correlations and regression analyses were performed to detect potential risk factors for treatment delay. Results Patients who received the histological confirmation of breast cancer at an external institution experienced a later therapy start than those patients who received the histological confirmation at the University Hospital Würzburg itself. (35.7 vs. 32.2 days). The interval between histological confirmation and the first consultation at the University Hospital Würzburg correlated statistically significant with age, distress and distance to the hospital. Conclusion Patients with an in-house diagnosis of breast cancer are treated more quickly than those whose diagnosis was confirmed in an external institution. We identified factors such as increased age, greater distance to the hospital as well as increased distress to prolong the time until start of oncological treatment. Intensified patient care should be offered to these subgroups.
The TLR signaling pathway and its regulatory factors in PTB. Membranous TLR4 binds to its ligands (like LPS) and activates the myD88-dependent pathway, whereas intracellular TLR3 responds to dsRNA and leads to the activation of the myD88-independent pathway. This causes transcription factors (IRF3, AP-1, CREB, and NFB) to translocate into the nucleus. IRF3 can promote the transcription of type II interferon, while AP-1, CREB, and NFκB trigger the production of inflammatory cytokines, chemokines, and type I interferon. Therefore, the activated TLR (mainly TLR4) signaling contributes to an inflammatory response in PTB. SNP, methylation, and ncRNA are all ways to regulate the TLR pathway. Some inflammatory genes exist SNPs variants or methylation differences between PTB and TB at their promoters. In addition, genes also transcribe non-coding RNAs, including lncRNA and miRNA, which can cause the regulation of the TLR signaling pathway in a transcriptional way. Exosomes are a way for cells to communicate with one another. Exosomes contain some ncRNAs, which can expel cells to participate in diverse physiological processes. As a result, exosome analysis in plasma can be employed as a non-invasive, easy, and promising approach to diagnose PTB
Introduction Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB. Methods An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review. Results Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling. Conclusion This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.
Hemoglobin concentration in g/dl before first intrauterine transfusion in cases of surviving versus non-surviving fetuses
Platelet count before first intrauterine transfusion in cases of surviving versus non-surviving fetuses
Purpose Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20⁺⁰ weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. Methods A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. Results A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19⁺³ (13⁺⁰–31⁺⁴) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20⁺⁰ weeks of gestation. Conclusion IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.
Flowchart for data collection and analysis of the patient records. GeQiK, Geschäftsstelle Qualitätssicherung im Krankenhaus (Office for Quality Assurance in Hospitals)
Detection rates relative to different symptoms and procedures
Purpose The aim of this study was to establish the rate at which routine postoperative renal ultrasonography is able to detect urinary tract injury following gynecological surgery. Methods A retrospective analysis was carried out for the study period 2015–2019 of all patients who had undergone subtotal or total hysterectomy, or radical hysterectomy or salpingectomy, salpingo-oophorectomy, or oophorectomy, and subsequently had a urinary tract injury. Results In a total of 2068 patients, 25 urinary tract injuries occurred (1.21%), including 21 urinary bladder lesions (1.02%) and four ureteral injuries (0.19%). The incidence of urinary tract injuries was 3% in oncologic procedures and 0.86% in procedures for benign disease. Nineteen injuries (76%) were diagnosed intraoperatively, and six injuries (24%) were clinically diagnosed after surgery. All of the patients had uneventful postoperative renal ultrasound examinations. Conclusion Routine postoperative renal ultrasonography was not capable of diagnosing urinary tract injuries after gynecologic surgery. Routine postoperative renal ultrasound examinations should, therefore, not be performed after gynecologic operations.
Objectives Despite the development of diagnosis and treatment methods, the psychological effects of infertility on women were not adequately addressed. This study investigated the effect of male and female factor infertility on women’s anxiety, depression, self-esteem, quality of life, and sexual function parameters. Methods In this prospective, cross-sectional study, 480 women [n = 234, with male factor infertility (MFI) (MFI group) and n = 246, with female factor infertility (FFI) (FFI group)], who could not conceive despite unprotected intercourse for 1 year, and 242 fertile healthy women (control group) who had children within the last 1 year were included. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Rosenberg Self Esteem Scale (RSES), Fertility Quality of Life (FertiQol) and Female Sexual Function Index (FSFI) questionnaires were used for patients’ evaluation. Results RSES, BAI and BDI-II scores were significantly higher and FSFI score was significantly lower in the FFI group compared to other groups. RSES, BAI and BDI-II scores were also significantly higher and FSFI score was significantly lower in the MFI group compared to the control group. FertiQol total score was significantly lower in the FFI group compared to the MFI group. RSES score was positively correlated with BDI-II and BAI scores; however, it was negatively correlated with FertiQol and FSFI scores. Conclusions The negative psychological effects of infertility are ignored by many centres, especially in the treatment process of infertility. Regardless of the infertility factor (male or female), we believe that psychological support should be given to all women to improve their life quality.
Systemic lupus erythematosus (SLE)—a most common disorder in women of reproductive age—has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.
Heat map showing the expression of genes for SARS-CoV-2 receptors and proteases in ovary and ovarian tissues from women with PCOS compared to controls.
Differential expression (Log2fold change values) of genes for SARS-CoV-2 receptors and spike protein processing enzymes in ovary obtained by independently reanalyzing the microarray gene expression datasets obtained from the GEO database. Microarray analysis was carried out in following samples a oocyte, (b–f) gonadotropin-stimulated mural granulosa cells. ACE2 angiotensin-converting enzyme II, BSG Basigin, DPP4 Dipeptidyl peptidase 4, CLEC4M C-type lectin domain family 4 member M, TMPRSS2 Transmembrane protease, serine 2; CTSB cathepsin B, CTSL cathepsin L
Relative expression of SCARFs in granulosa cells.
Relative genes expression levels of SARS-CoV-2 receptors (ACE2, BSG, CLEC4M, DPP4) and spike protein processing enzymes (CTSB, CTSL and FURIN) in MGCs (a, b) and CGCs (c, d) compared between PCOS and control groups. Fold change was evaluated using the 2−ΔΔCt method. Expression was normalized to the 18S rRNA gene as an endogenous control and granulosa cells calibrator sample. Bar graphs represent “mean ± SEM” and *P < 0.05 considered significant. Data are analyzed using the Mann–Whitney U test. MGCs mural granulosa cells, CGCs cumulus granulosa cells, ACE2 angiotensin-converting enzyme II, BSG Basigin, DPP4 Dipeptidyl peptidase 4, CLEC4M C-type lectin domain family 4 member M, TMPRSS2 Transmembrane protease, serine 2; CTSB cathepsin B, CTSL cathepsin L
Purpose Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is global pandemic with more than 5 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs), suggesting they may be susceptible to SARS-CoV-2 infection; however, the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease, etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women. Materials and methods SCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expressions of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF). Results Microarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types. Conclusion Human ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicates that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic.
Objectives Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, we aimed to examine the effects and mechanisms of NYPQ on angiogenic ability in EMS. Study design EMS rats were established with estradiol valerate and autologous transplantation. EMS rats were intraperitoneally injected with chloroquine (CQ, 40 mg/kg), rapamycin (RAPA, 1 mg/kg), and monoclonal antibody VEGF (anti-VEGF, 3 mg/g/d) or administered 5, 10, 20 mg/g/d NYPQ decoction through oral gavage for 4 weeks, respectively. By the before and end of the treatment period, the volume of the endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, and lumen formation experiment, respectively. The expression levels of VEGF, autophagy-/apoptosis-/PPARγ/NF-κB- pathway-related proteins in endometrium tissues or HUVECs were detected by western blot assays. Results The autophagy agonist rapamycin reduced the lesion size, the microvessel density, and VEGF expression, and promoted the production of autophagosomes and the expression of autophagy-related proteins, while the autophagy inhibitor chloroquine had the opposite effects. In vivo, NYPQ could dose-dependently reduce lesion volume and microvessel density, ameliorate histopathological features and promote autophagosome production of ectopic endometrium. Moreover, serum-containing NYPQ could significantly inhibit the cell viability and tube formation of HUVECs and elevate HUVECs apoptosis. Besides, NYPQ significantly reduced VEGF and promoted autophagy-/apoptosis-related protein expressions. Also, NYPQ might promote autophagy and inhibit angiogenesis by activating the PPARγ/NF-κB pathway. Conclusions Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway.
a A4 and AMH levels in girls with or without OM in the presence or absence of PCOM. In adolescent girls with OM who also had PCOM, AMH and A4 levels did not differ significantly from those without PCOM. Similar results were obtained in adolescent girls with regular menstruation. OM: oligomenorrhea, RM: regular menstruation, PCOM: Polycystic ovary morphology b Androstenedione (A4) and anti-Mullerian hormone (AMH) levels in girls with or without oligomenorrhea in the presence or absence of hirsutism. When oligomenorrhea and hirsutism were concomitant, significantly higher AMH and A4 levels were present
AMH and A4 levels according to clinical features of PCOS in adolescent girls with and without oligomenorrhea (OM). In adolescents with oligomenorrhea, androstenedione levels are significantly higher in the presence of hirsutism. AMH levels are significantly higher in girls with OM + hirsutism+ PCOM. OM: oligomenorrhea, RM: regular menstruation, Group1: OM or RM only; Group2: OM or RM+ hirsutism; Group3: OM or RM + polycystic ovary morphology (PCOM); Group4: OM or RM + hirsutism+ PCOM
Purpose To determine the variation in anti-Mullerian hormone (AMH) and androstenedione (A4) concentrations in adolescent girls, with or without menstrual cycle disorder in relation to phenotypic features of. PCOS. Methods Adolescent girls (n = 129), age range 14–19 years, were recruited in the cohort study. All participants were in the 4th or 5th year after menarche. Sixty-eight had menstrual irregularities, usually oligomenorrhea (OM), and 61 had regular menstruation (RM). AMH and A4 concentrations were measured. Hirsutism was recorded. Polycystic ovarian morphology (PCOM) was evaluated by transabdominal pelvic ultrasonography. Polycystic ovary syndrome (PCOS) features were defined according to Rotterdam consensus criteria. Results AMH and A4 were significantly higher in adolescent girls with OM than in girls with RM (p < 0.05). A4 and body mass index (BMI) of adolescents with OM was significantly higher in those with hirsutism than those without hirsutism (p = 0.01 and 0.008, respectively). There was a positive correlation between A4 and BMI (r: 0.327, p < 0.01). Logistic regression showed that the frequency of OM in the presence of PCOM was 10.8 times (95% CI 2.04–12.09) compared to those without PCOM. The highest AMH concentrations were found in girls with OM, hirsutism, and PCOM (p < 0.05). Conclusions AMH and A4 are elevated in adolescents with oligomenorrhoea. High A4 is more prominent in the presence of hirsutism and is associated with increased BMI. PCOM, increases the likelihood of oligomenorrhea by about 10 times. AMH increase as the combination of clinical features of PCOS increases in adolescents with menstrual irregularity.
Classification of Cohort 1) with hormone replacement therapy (HRT) according to systemic (transdermal/oral/free combination1) and vaginal
Sample description based on a patient flow diagram
Proportion of patients and number of physician changes* (within the specialty group of gynaecologists and family physicians) at baseline (left) and in the first year of follow-up (right)
Purpose The transition from the fertile phase of life to menopause is associated with numerous physical changes. Hormone replacement therapy (HRT), as the most effective and efficient form of drug treatment, involves the use of oestrogens and progestins with the aim of increasing health-related quality of life through symptom reduction, sleep improvement and affect enhancement. Methods The medical care situation and disease burden of menopausal women was investigated by means of a survey of 1000 women aged 45–60 years on the topics of quality of life, menopause and HRT and a quantitative, longitudinal healthcare study based on an anonymised and age- and sex-adjusted Statutory Health Insurance (SHI) routine data set with approximately four million anonymous insured persons per year. Results Out of more than half a million women aged 35–70 years, and with statutory health insurance, ( n = 613,104), 14% ( n = 82,785) had climacteric disorder documented as a first diagnosis in 2014. The proportion of women with the climacteric disorder, who were prescribed HRT on an outpatient basis, was 21%; according to the forsa survey, 50% of the women surveyed felt moderate to poorly/very poorly informed about treatment options. Conclusion Findings from the health insurance research conducted with different data sources (survey and SHI claims data) indicate the need for increasing awareness and providing an early and informative education on HRT and its risks and benefits.
Expression of miR-383-5p and CIRP in GCs of PCOS patients. a Expression of miR-383-5p in ovarian granulosa cells (GCs) of PCOS patients was decreased. b ROC curve analysis showed that the predictive value of miR-383-5p for PCOS. c The expression of CIRP mRNA in GCs from PCOS patients was detected by qRT-PCR analysis. d Spearman correlation analysis was used to evaluate the correlation between miR-383-5p and CIRP. *P < 0.05 compared with the non-PCOS group
MiR-383-5p suppressed cell proliferation and promoted apoptosis. a Levels of miR-383-5p in each group after transfection, as detected by qRT-PCR. b Cell proliferation was performed using CCK-8 assay at 48, 72, and 96 h after cell transfection. c and d Apoptosis rate of KGN cells in each group, as measured using flow cytometry. e and f Levels of Bcl-2, Bax, and cleaved caspase 3 after transfection, as detected by western blot analysis. *P < 0.05 compared with the respective negative controls
CIRP was a direct target of miR-383-5p. a The binding sequence for miR-383-5p in the 3′-untranslated region of CIRP. b Dual-luciferase reporter assay was performed to confirm the relationship between miR-383-5p and CIRP. c The expression of CIRP mRNA was assessed in cells transfected for overexpression or knockdown of miR-383-5p using qRT-PCR analysis. d The expression of CIRP protein was assessed in cells transfected for overexpression or knockdown of miR-383-5p using western blot analyses. *P < 0.05 compared with the respective negative controls
CIRP accelerated proliferation and suppressed apoptosis, and partially reversed the effect of miR-383-5p in the KGN cells. a and b Levels of CIRP in each group after transfection, as detected by western blot analysis. c Cell proliferation was evaluated using the CCK-8 assay at 48, 72, and 96 h after transfection. d and e Apoptosis rate of KGN cells in each group, as measured using flow cytometry. f and g Levels of Bcl-2, Bax, and cleaved caspase 3 after transfection, as detected by western blot analysis. *P < 0.05 compared with the respective negative controls
MiR-383-5p promotes apoptosis through the PI3K/AKT signal pathway by targeting CIRP. a and b MiR-383-5p suppresses the PI3K/AKT signal pathway. c and d The CIRP overexpressing plasmid could activate this signal pathway, and mitigated the inhibitory effect of miR-383-5p. e and f LY294002 inhibited the PI3K/AKT signaling pathway. g and h Expression of Bcl-2 was reduced, whereas that of Bax and cleaved caspase 3 was increased upon treatment of cells overexpressing CIRP with LY294002. *P < 0.05 compared with the respective negative controls
Purpose To detect miR-383-5p and cold-inducible RNA binding protein (CIRBP, CIRP) expression in patients with polycystic ovary syndrome (PCOS) and explore the mechanism underlying their effect on apoptosis in ovarian granulosa cells (GCs). Methods GCs were extracted from follicular fluid from 101 patients. MiR-383-5p and CIRP expression were assessed by quantitative real time polymerase chain reaction analysis. Correlation between them was assessed by Spearman correlation analysis. The potential of using miR-383-5p expression for discriminating PCOS and non-PCOS patients was predicted by receiver operating characteristic curve analysis. Proliferation and apoptosis of KGN cells transfected for miR-383-5p overexpression or knockdown was evaluated using cell counting kit-8 assay, flow cytometry, and western blot analysis. CIRP was identified as a direct target of miR-383-5p, and verified by dual-luciferase reporter assay. Results The expression level of miR-383-5p was decreased and CIRP mRNA was increased in PCOS patients. The expression of miR-383-5p was correlated negatively with body-mass index, basal luteinizing hormone and testosterone levels, luteinizing hormone/follicle-stimulating hormone ratio, and the number of retrieved and metaphase II oocytes. MiR-383-5p had sufficient potential for prediction of PCOS. There was a negative correlation between the expression of miR-383-5p and CIRP. Overexpression of miR-383-5p enhanced the apoptosis of KGN cells. CIRP reversed the effect of miR-383-5p on promotion of apoptosis. MiR-383-5p mimics could suppress the PI3K/AKT signaling pathway, which was activated by the CIRP overexpressing plasmid. Conclusions MiR-383-5p promoted apoptosis of ovarian GCs through the PI3K/AKT signaling pathway by targeting CIRP.
Background We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) to clarify if lower number of oocytes is a drawback for proceeding to C-IVF. Materials and methods In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤ 3 cumulus–oocyte complexes available for fertilisation were analysed. Exclusion criteria were: woman age > 42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1, n = 77); ICSI non-male factor (Group 2, n = 65); ICSI male factor-ICSI/MF n = 49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. Results Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85.68%, 72.58%, 73.33% respectively, p = 0.004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20.42%, 28.49%, 23.33% respectively, p = 0.407) and live birth rates (26.8%, 30.6%, 31.1%, respectively, p = 0.643). Conclusion In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient’s previous history regardless of the ovarian reserve.
Background Endometrial carcinoma (EC) is a common female reproductive malignant tumor. Circular RNAs (circRNAs) have been reported to participate in tumorigenesis, including EC. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circ_0002577 in EC. Methods The expression levels of circ_0002577, miR-126-5p, and metastasis associated in colon cancer 1 (MACC1) was determined by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was quantified by western blot assay. The proliferation of EC cells was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The migration and invasion of EC cells was measured by transwell assay. The apoptosis was determined by flow cytometry assay. Dual-luciferase reporter assay and RNA pull-down assays were performed to confirm the relationship between miR-126-5p and circ_0002577 or MACC1. The influence of circ_0002577 inhibition on tumor growth was assessed by xenograft experiment. Results Circ_0002577 and MACC1 were increased while miR-126-5p was decreased in EC tissues and cells. Loss-of-functional experiment revealed that silencing of circ_0002577 inhibited the proliferation, migration, and invasion while induced apoptosis of EC cells, which were overturned by overexpression of MACC1. The upregulation of miR-126-5p also impeded proliferation and mobility while induced apoptosis of EC cells. MiR-126-5p, negatively regulating MACC1 expression, was a functional target of circ_0002577 in EC cells. Moreover, we also confirmed that suppression of circ_0002577 repressed tumor growth in vivo. Conclusion The contributions of the circ_0002577 in EC were contributed to its interactions with miR-126-5p and MACC1, which offered a new perspective to the roles of circ_0002577 in EC.
Upper—scheme of vulvar clock mapping: continuous line represents the visual lesion borders. Pointed line represents the edge at 2 cm from the lesion. The third line represents the edge at 4 cm from the lesion. Points indicate sites of biopsies. Below—example of histological samples of a series of A–B–C biopsies with presence of in situ VPD on A and B samples, and C without disease (HE staining)
Scheme of vaginal clock mapping. Points indicate sites of biopsies. Points A represent the biopsy at the vestibule; B at 2 cm from A and C at 4 cm from the vestibule. At each site (A–B and C), biopsies are performed at 3–6–9 and 12 o’clock
Scheme of radical surgical plan: black points indicate positive biopsies at preoperative clock mapping. Black pointed line represents the planned resection area after clock mapping findings
Main results diagram. Group A: patients with biopsies positive for Paget disease inside the visible lesion. Group B: patients with biopsies positive for Paget disease outside the visible lesion. For each treatment phase, (1) clock mapping and (2) surgery the number of patients upstaged after pathology report is indicated; respectively, 11 cases after clock mapping and four after definitive surgery. For each group, definitive margins are stratified as negative and positive. Moreover, positive margins are classified in: (a) positive on medial structures, (b) positive on medial structures and lateral skin, (c) positive on lateral skin
Introduction Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget’s disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. Materials and methods All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o’clock positions, and in the vagina. Patients with positive biopsies “only inside” or “also beyond” the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. Results A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. Conclusions Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.
Characteristics of CD44⁺ ovarian CSCs. Sphere formation assay indicated that CD44⁺ ovarian CSCs has higher spheroid formation ability than ovarian cancer cells (greater size and number of spheres) (A and B). qRT-PCR detection of the expression of NANOG, OCT4 and SOX2 in CD44⁺ ovarian CSCs and ovarian cancer cells (C). Western blot detection of the expression of NANOG, OCT4 and SOX2 in CD44⁺ ovarian CSCs and ovarian cancer cells (D and E). *P < 0.05, **P < 0.01 and ***P < 0.005
Distinct expression profile of miRNAs in CD44⁺ ovarian CSCs. The Venn diagram shows the number of different miRNAs (A). Hierarchical clustering of miRNAs with good consistency in CD44⁺ A2780 cell lines and CD44⁺SKOV3 cell lines. ‘Red’ indicates high relative expression, and ‘green’ indicates low relative expression (B). Among these miRNAs, the levels of 11 miRNAs were upregulated, and those of 7 miRNAs were downregulated. The level of differentially expressed miRNAs in CD44⁺ ovarian CSCs was tested by qRT-PCR and compared with that in ovarian cancer cells (C). *P < 0.05, **P < 0.01 and ***P < 0.005
GO analysis and pathway analysis of the differentially expressed miRNAs. Top ten GO terms of biological processes for different miRNAs between CD44⁺ ovarian CSCs and ovarian cancer cells (A). Top ten GO terms of cellular components for differentially expressed miRNAs between CD44⁺ ovarian CSCs and ovarian cancer cells (B). Top ten GO terms of molecular components for differentially expressed miRNAs between CD44⁺ ovarian CSCs and ovarian cancer cells (C). Top ten KEGG pathways for differentially expressed miRNAs between CD44⁺ ovarian CSCs and ovarian cancer cells (D). The analyses show that these miRNAs are involved in regulating stem cell-like characteristics in CD44⁺ ovarian CSCs
MiR-181a-2-3p is involved in regulating stem cell-like characteristics in CD44⁺ ovarian CSCs in vitro. MiR-181a-2-3p overexpression and inhibition in CD44⁺ ovarian CSCs (A); miR-181a-2-3p modulates the expression of NANOG, OCT4 and SOX2 in CD44⁺ ovarian CSCs tested by qRT-PCR (B); miR-181a-2-3p modulates the self-renewal ability of CD44⁺ ovarian CSCs tested by sphere formation (C–D). *P < 0.05, **P < 0.01 and ***P < 0.005
MiR-181a-2-3p negatively regulates the stem cell-like properties of CD44⁺ ovarian CSCs by targeting EGR1. Kaplan- Meier Plotter database showed that EGR1 expression have significant with survival of ovarian cancer patients (A). The expression levels of EGR1 in CD44⁺ ovarian CSCs transfected with miR-181a-2-3p mimics, inhibitor and negative control were determined by qRT-PCR (B). The expression levels of EGR1 in CD44⁺ ovarian CSCs transfected with miR-181a-2-3p mimics, inhibitor and negative control were determined by western blot (C–D). *P < 0.05, **P < 0.01 and ***P < 0.005
Purpose The aim of our study was to investigate microRNA (miRNA) expression profiles in CD44⁺ ovarian cancer stem cells (ovarian CSCs). Methods In this study, we enriched CD44⁺ ovarian CSCs using magnetic activated cell sorting (MACS). A combination of real-time quantitative PCR (qRT-PCR), western blot and sphere formation assays was used to demonstrate stem cell-like properties. RNA sequencing was used to detect the miRNA expression profiles in CD44⁺ ovarian CSCs. Transient transfection, qRT-PCR, western blot and sphere formation assays were further used to test the function of miR-181a-2-3p. Results We found that CD44⁺ ovarian CSCs showed enhanced sphere formation and expression of stemness-associated genes (NANOG, OCT4, SOX2) compared to ovarian cancer cells. The RNA sequencing results showed that the miRNA expression profiles of CD44⁺ ovarian CSCs were different from those of ovarian cancer cells. GO and KEGG pathway analyses indicated that these miRNAs regulate stem cell-like properties in CD44⁺ ovarian CSCs. In addition, miR-181a-2-3p negatively regulates the stem cell-like properties of CD44⁺ ovarian CSCs by targeting EGR1. Conclusion Our data suggest that miRNAs play important roles in regulating the stem cell-like properties of CD44⁺ ovarian CSCs.
Example of western blot membranes after stimulation with different concentrations of MTE or the control group and incubation with β-actin and PPARγ antibodies. The respective bands are numbered [(1) 0 µg/ml; (2) 5 µg/ml; (3) 10 µg/ml; (4) 50 µg/ml] and marked with black boxes.
WST-1 assay of T47D cells stimulated with MTE. The grey bars represent the optical density of T47D cells after the incubation with different concentrations of MTE (5, 10 and 50 µg/ml) for 72 h. The white bars represent the control group. The top of each bar represents the mean ± standard error (SE). MTE induced a significant reduction of cell proliferation at every concentration. Significant results are linked and marked with asterisks (p < 0.05*, p < 0.01**, p < 0.001***)
The bar chart represents the relative PPARγ expression on mRNA level in T47D cells after incubation with three different concentrations of MTE (5, 10 and 50 µg/ml) or the control solution for 2 h. mRNA levels were detected via TaqMan® real-time PCR. The values on the y axis are show ratios of stimulated and control expression levels. The top of each bar represents the mean ± SE. Statistical significance was achieved at the highest concentration of MTE (p = 0.029) and is marked with one asterisks
The bar chart shows the PPARγ protein expression in T47D cells after stimulation with different concentrations of MTE compared to control. The top of each bar represents the mean ± SE. MTE induced a significant upregulation of PPARγ expression on protein level at MTE concentrations of 10 µg/ml and 50 µg/ml. Significant differences between groups are linked and marked with asterisks (p < 0.001***)
Purpose In the following work, we investigated the nuclear peroxisome proliferator-activated receptor gamma (PPARγ)-dependent proliferation behavior of breast cancer cells after stimulation with matcha green tea extract (MTE). Methods T47D cells were stimulated with MTE at concentrations of 5, 10 and 50 µg/ml. Cell viability was assessed using a WST-1 assay after an incubation time of 72 h. PPARγ expression was quantified at the gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. Results The WST-1 test showed a significant inhibition of viability in T47D cells after 72 h at 5, 10 and 50 µg/ml. The PCR showed an overexpression of PPARγ in T47D cells in all concentrations. At the concentration of 50 µg/ml the expression was significantly increased ( p < 0.05). The WB demonstrated a significant quantitative increase of PPARγ at protein level with MTE concentrations of 10 and 50 µg/ml. In addition, there was a negative correlation between the overexpression of PPAR γ and the inhibition of proliferation. Conclusion MTE decreases the cell viability of T47D cells and furthermore leads to an overexpression of PPARγ on protein and mRNA level.
Kaplan–Meier survival curves for overall survival according to the hypersensitivity reactions
Purpose We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). Methods This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. Results Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 − 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). Conclusion In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.
PurposeThe present study aims to develop a new high-resolution imaging system for the early diagnosis of cervical neoplasia based on increased vessel density of the cervical tissue.Methods An optical device was developed to obtain high contrast and resolution images of vascular structures of the cervix in the present study. The device utilizes a telecentric lens to capture cervix images under light illumination with a wavelength of 550 nm emitted from LEDs. Images were obtained using the telecentric lens with or without acetic acid application to the cervix. Image processing algorithms were used to contrast and extract the skeleton of the vascular structures on the cervix. In the evaluation of the vascular density, the cervical images were divided into 12 o’clock positions, and the fractal dimension of the vascularity was calculated for each dial area between the o’clock positions. The region with the largest fractal dimension was accepted as the region with the highest probability of lesion. The range of vessel sizes was split into small classes of “bins” for each dial area with the highest fractal dimension. To validate the system’s success in differentiating between normal and HSIL lesions, forty five patients who underwent colposcopy and biopsy were included in a pilot study.ResultsThe system correctly classified four HSIL cases out of five and failed to detect one HSIL case, achieving an accuracy rate of 97.8% with an 80% sensitivity and 100% specificity.Conclusion The developed high-resolution optical imaging system may potentially be used in detecting cervical neoplasia just before the biopsy and reduce the number of false-positive cases.
Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.
Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.
a The number of active cases and total death with COVID-19 infection in the world, and b the COVID-19 daily cases outside of China from 22 Jan 2020 to 20 Mar 2020. Retrieved from
The most common symptoms detected in pregnant women with COVID-19 infections
Chest CT scans of a 32-year-old Iranian pregnant woman with COVID-19 at 36 weeks gestation at admission time (a), and 3 days after starting antibiotic-antiviral therapy (b)
summary of case reports on the infection risk of COVID-19 for pregnant women and newborns
Background The establishment of a risk-appropriate care approach for pregnant women and newborn infants under the COVID-19 pneumonia is vital to prevent the main pregnancy complications.Objectives and designThis study reviewed the vertical transmission (VT) potential of COVID-19 pneumonia in pregnant women. Key-related symptoms and adverse clinical outcomes for mothers and infants before and after childbirth were summarized. Some practical therapies and preventive health solutions were also proposed.ResultsThere was a high susceptibility in pregnant women to COVID-19 infection, especially in the third trimester of pregnancy. The most common symptoms in 22–40-year-old patients infected with COVID-19 were fever (87.6%), cough (52.3%), dyspnea (27.6%), fatigue (22.4%), sore throat (13.5%), malaise (9.4%), and diarrhea (3.4%), respectively. The viral infection led to an increase in preterm labor and cesarean delivery without any intrauterine infection and severe neonatal asphyxia. No infection in the newborn infants was reported despite a high risk of the VT phenomenon. The most important therapies were the reception of antiviral and antibiotic drugs, oxygenation therapy, psychological interventions, and food supplements with health-promoting effects. The best proposed medical strategies to control the COVID-19 infection were bi-monthly screening and following-up the mothers’ and fetuses’ health, not using the potent broad-spectrum antibiotics and corticosteroids, providing the delivery room with negative pressure for emergency cesarean section, and the immediate isolation of newborns after childbirth without direct breastfeeding.Conclusion Babies with respiratory problems may be born to some mothers with COVID-19, who have weak immune systems. Thus, the virus transmission cycle should be disrupted to prevent adverse maternal and fetal outcomes by integrating individual health guidelines, efficient medical care therapies, and hospital preventive practices.
Flow diagram of the study selection process
Risk of bias assessment
Kaplan–Meier analysis illustrating patient age and OS
Kaplan–Meier analysis illustrating tumor stage and OS
Kaplan–Meier analysis illustrating recurrence location and OS
Background Ovarian adult granulosa cell tumours are low-grade malignant sex cord–stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT.Methods Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher’s exact test and Kaplan–Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant.ResultsEleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan–Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively.Conclusions In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.
PurposeThe objective of this study was to identify risk and protective factors related to general prenatal distress and COVID-19-specific prenatal distress to inform intervention targets among women pregnant during the COVID-19 pandemic.Methods The study relied on data obtained from U.S. pregnant women (N = 701) who participated in the Perinatal Experiences and COVID-19 Effects (PEACE) Study from May 21 to October 3, 2020. The present cross-sectional study examined the potential risk and protective factors associated with different features of prenatal distress among U.S. pregnant women during the COVID-19 pandemic.ResultsApproximately two-thirds of expectant mothers indicated being more stressed about going to the hospital because of COVID-19. Generalized anxiety and PTSD were associated with higher levels of general and COVID-19-specific prenatal distress. Depression symptoms were associated with higher general prenatal distress. Higher levels of distress tolerance were associated with lower levels of general prenatal distress (B = − 0.192, p < .001) and COVID-19-specific prenatal distress (B = − 0.089, p < .05). Higher levels of instrumental social support were marginally associated with lower COVID-19-specific prenatal distress (B = − 0.140, p < 0.1).Conclusion Findings draw attention to prenatal distress experiences during the COVID-19 pandemic, including new types of distress arising from the pandemic itself. Women might benefit from the introduction of interventions such as mindfulness-based or relaxation therapy. Coverage of responsibilities and financial assistance is particularly needed during the COVID-19 pandemic. Limitations include a majority White and high socioeconomic sample. These findings provide specificity regarding potential targets for addressing prenatal distress.
Schematic flowchart of patient inclusion in the study
Key message Spontaneous labor onset, epidural anesthesia and prior cesarean for non-arrest disorders are strong predictors of successful vaginal birth after cesarean in women delivering a macrosomic fetus. PurposeLower rates of successful vaginal birth after cesarean in association with increasing birthweight were previously reported. We aimed to determine the factors associated with successful trial of labor after cesarean (TOLAC) among primiparous women with fetal macrosomia.MethodsA retrospective cohort study conducted during 2005–2019 at two university hospitals, including all primiparous women delivering a singleton fetus weighing ≥ 4000 g, after cesarean delivery at their first delivery. A multivariate analysis was performed to evaluate the characteristics associated with TOLAC success (primary outcome).ResultsOf 551 primiparous women who met the inclusion criteria, 50.1% (n = 276) attempted a TOLAC and 174 (63.0%) successfully delivered vaginally. In a multivariate analysis, spontaneous onset of labor (aOR [95% CI] 3.68 (2.05, 6.61), P < 0.001), epidural anesthesia (aOR [95% CI] 2.38 (1.35, 4.20), P = 0.003) and history of cesarean delivery due to non-arrest disorder (aOR [95% CI] 2.25 (1.32, 3.85), P = 0.003) were the only independent factors associated with TOLAC success. Successful TOLAC was achieved in 82.0% (82/100) in the presence of all three favorable factors, 61.3% (65/106) in the presence of two factors and 38.6% (27/70) in the presence of one or less of these three factors (P < 0.001).Conclusion Spontaneous onset of labor, epidural anesthesia and prior cesarean delivery due to non-arrest disorders were independently associated with higher vaginal birth after cesarean rate among women with fetal macrosomia, with an overall favorable success rate in the presence of these factors. These findings should be implemented in patient counseling in those contemplating a vaginal birth in this setting.
Study flow chart. VBAC, vaginal birth after cesarean section
PurposeTo compare the rate of vaginal birth between double-balloon catheter and oxytocin alone for induction of labor in women with one previous cesarean section and an unfavorable cervix.Materials and methodsA retrospective and observational study was conducted from 2013 to 2017, at the Saint-Etienne University Hospital where women received induction with a double-balloon catheter for 12 h and at the Grenoble Alpes University Hospital where women received induction with a low‐dose oxytocin infusion. Primary outcome was the rate of vaginal birth.ResultsOut of 1920 women eligible for attempting a vaginal birth after one previous cesarean section, 501 had a labor induction. Among women with an unfavorable cervix, 160 received a double-balloon catheter in Saint Etienne and 152 received oxytocin alone in Grenoble. The vaginal birth rate was higher in the double-balloon catheter group (61% versus 47% in the oxytocin group). An induction of labor with oxytocin alone reduced chances of vaginal birth (aOR 0.38 CI-95% [0.22–0.66]) compared to cervical ripening with double-balloon catheter. The perinatal morbidity was similar in the two groups. There was, however, 3.9% uterine rupture in the oxytocin group versus 0.6% in the double-balloon group (p = 0.11).Conclusion For induction of labor in women with one previous cesarean section and with unfavorable cervix, cervical ripening with a double-balloon catheter increases the rate of vaginal birth without increased risk of uterine rupture.
Purpose To determine the factors associated with successful trial of labor after cesarean (TOLAC) among grand-multiparous (GMP) women. Methods A retrospective cohort study was conducted, including all GMP women (≥ 5 deliveries) undergoing TOLAC during 3/2011 and 6/2020, delivering a singleton cephalic newborn. Factors associated with successful vaginal delivery were examined by multivariable analysis. Results Overall, 381/413 (92.2%) GMP succeeded TOLAC. Maternal characteristics did not differ between TOLAC success and TOLAC failure groups. Previous cesarean delivery characteristics did not differ between study groups. The median number of previous vaginal births after cesarean was 2 [interquartile range 1–4]. Gestational age at TOLAC was lower in the success group (mean 371/7 ± 36/7 vs. 385/7 ± 31/7 weeks, p = 0.028). A lower rate of modified Bishop score < 4 was associated with TOLAC success [149 (39.1%) vs. 22 (69%), odds ratio (OR) 95% confidence interval (CI) 0.29 (0.13–0.64), p = 0.001]. The rate of induction of labor was higher in the TOLAC failure group [120 (31.5%) vs. 17 (53%), OR 95% CI 0.40 (0.19–0.83), p = 0.013]. The rate of oxytocin administration was higher in the TOLAC failure group [94 (24.7%) vs. 15 (47%) OR (95% CI) 0.37 (0.17–0.77), p = 0.006]. The duration of rupture of membranes was negatively associated with TOLAC success. Neonatal and maternal adverse outcomes did not differ between study groups. In multivariable logistic regression analysis, only the duration of rupture of membranes and modified Bishop score < 4 were independently associated with TOLAC success [adjusted OR (95% CI) 0.98 (0.96–0.99), p = 0.027 and 0.40 (0.16–0.97), p = 0.044]. Conclusion TOLAC among GMP has a very-high success rate. Shortening the duration of ruptured membranes is a modifiable factor that may be associated with increased TOLAC success rates.
Flowchart of the study sample
Willingness of the pregnant group to receive the COVID-19 vaccination. At the time of recruitment, the minority (13.8%) would decide to receive the COVID-19 vaccination. However, when asked whether they would be vaccinated if a scientific study would provide evidence for the safety of the vaccination 47.2% of the pregnant sample would decide to receive the vaccination
The willingness to receive the COVID-19 vaccinations significantly depends on the group. Less women in the pregnant group would decide to receive the vaccination that women in the breastfeeding group
In both groups, the willingness to be vaccinated is dependent on whether women scored low or high on the visual analogue scales evaluating how anxious they are to be infected and to develop severe symptoms, respectively. In the pregnant group (A) and the breastfeeding group (B), the women in the high anxiety infection group and high anxiety symptoms group would decide to receive the COVID-19 vaccination more often than the low anxiety groups, whereas a higher percentage in the low anxiety groups would decide not to receive the vaccination than the high anxiety groups
Purpose The COVID-19 vaccination is probably the most important source to fight the COVID-19 pandemic. However, recommendations and possibilities for vaccination for pregnant and breastfeeding women are inconsistent and dynamically changing. Methods An anonymous, online, cross-sectional survey was conducted among pregnant and breastfeeding women in Germany between 30th March and 19th April 2021 addressing COVID-19 vaccination attitudes including the underlying reasons for their decision. Additionally, anxiety regarding a SARS-CoV-2 infection and a symptomatic course of the infection were evaluated. Results In total, 2339 women ( n = 1043 pregnant and n = 1296 breastfeeding ) completed the survey. During pregnancy the majority (57.4%) are not in favour of receiving the vaccine, 28.8% are unsure and only 13.8% would get vaccinated at the time of the survey. In contrast, 47.2% would be in favour to receive the vaccine, if more scientific evidence on the safety of the vaccination during pregnancy would be available. Breastfeeding women show higher vaccination willingness (39.5% are in favour, 28.1% are unsure and 32.5% not in favour). The willingness to be vaccinated is significantly related to the women’s anxiety levels of getting infected and to develop disease symptoms. Main reasons for vaccination hesitancy are the women’s perception of limited vaccination-specific information, limited scientific evidence on vaccination safety and the fear to harm the fetus or infant. Conclusions The results provide important implications for obstetrical care during the pandemic as well as for official recommendations und information strategies regarding the COVID-19 vaccination.
Purpose The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. Methods A prospective case–control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal–Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17–20 weeks (only in early GDM cases), 26–30 weeks, 32–35 weeks and 36–39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). Results GDM group had significantly lower values of CO and SV than controls from the early third trimester (26–30 weeks) until term (p < 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p < 0.001). GDM women showed also lower INO values than controls in all assessments. Conclusions A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow‐up.
Origin of data set
Bleeding duration (Kaplan–Meier curve)
Purpose To improve counseling of women by reporting bleeding characteristics at home after medical management of an early pregnancy loss (EPL) with mifepristone and misoprostol, and to evaluate occurring bleeding patterns as a prognostic tool. Methods This prospective two-center observational cohort study enrolled 197 women who presented with an EPL (embryonic or anembryonic miscarriage) from December 2017 to April 2019 and chose a home-based medical management with 200 mg mifepristone and 800 mcg misoprostol. From the day of mifepristone intake, the strength of vaginal bleeding was recorded daily for 2 weeks by the patient herself using a diary sheet. Treatment success was defined as no histologically confirmed retained products of conception (RPOC) within 3 months. After considering all drop-out criteria, 154 women were included in the analysis. Results 40.0% of patients (95% CI 30.4–49.6) already reported bleeding onset in the time period between the intake of mifepristone and misoprostol. The median duration of vaginal bleeding including spotting was 13 days. The chance of RPOC was about sixfold (OR 6.06, 95% CI 2.15–17.10) in the group of persistent bleeding after 2 weeks compared to the group with a terminated bleeding at that time. Exploratory regression analysis indicated association of higher serum levels of leukocytes at treatment start with RPOC (p = 0.013). Conclusions Terminated bleeding after 2 weeks is a useful indicator for successful medical induction of EPL. Women undergoing medical treatment with mifepristone must be informed about the high frequency of bleeding onset before misoprostol intake. Clinical trial registration DRKS—German Clinical Trials Register, ID: DRKS00013515, registration date 05.12.2017.
a Villitis of unknown etiology, high-grade (Hematoxylin and Eosin, magnification is 100×). On the left of the photomicrograph, normal villi are present. On the right, a focus with lymphohistiocytic inflammation and destruction of terminal villi and stem villi is visible. Placenta from the 40th gestational week, perinatal complications were a pathologic CTG and FGR. b Chronic deciduitis with plasma cells (Hematoxylin and Eosin, magnification is 100×). The decidua basalis on the left of the photomicrograph shows a dense lymphoplasmacytic infiltrate that does not involve the adjacent villi on the right. Placenta from the 39th gestational week with bleeding and placental abruption
a Chronic chorioamnionitis (Hematoxylin and Eosin, magnification is 20×). A dense lymphocytic infiltrate is present beneath the amnion epithelium. The inflammation involves the amnion, chorion leave and the decidua capsularis. Placenta from the 33th gestational week with preterm birth. b Chronic histiocytic intervillositis (Hematoxylin and Eosin, magnification is 200×). In the intervillous space histiocytic cells with round, elongated and sometimes folded nuclei can be detected. There is no infiltration of the villi which show an intact morphology. Placenta from the 26th gestational week, intrauterine fetal demise, the stillborn had a weight below the 3rd percentile. c Eosinophilic/T-cell chorionic vasculitis (Hematoxylin and Eosin, magnification is 100×). On the left, the lumen of a large vessel of the chorionic plate is visible. There is a predominantly lymphocytic inflammation with many eosinophilic granulocytes and partial destruction of the vessel wall resulting in necrotic areas with fibrin. Placenta from the 38th gestational week with preterm rupture of membranes. History of intrauterine fetal demise with villous dysmaturity
Distribution of the major perinatal complications hypertensive disorders of pregnancy (HDP), FGR and preterm birth in the different histologically defined lesions. Early-onset (< 34th gestational age) and late-onset (≥ 34th gestational age) manifestations were considered
Purpose Chronic inflammatory disorders of the placenta, in particular villitis of unknown etiology (VUE), chronic deciduitis (CD), chronic chorioamnionitis (CC), chronic histiocytic intervillositis (CHI), and eosinophilic/T-cell chorionic vasculitis (ETCV) can exclusively be diagnosed histologically. Using a standardized procedure for submission and pathological–anatomical examination of placentas in a single perinatal care center, we analyzed the association of chronic placental lesions to perinatal complications. Methods We reviewed all singleton placentas and miscarriages that were examined histologically over a period of ten years after having implemented a standardized protocol for placental submission in our hospital. Cases with chronic inflammatory lesions were identified, and clinical data were analyzed and compared with a focus on preterm birth, hypertensive disorders, and fetal growth restriction and/or fetal demise. Results In 174 placentas, at least one of the chronic inflammatory entities was diagnosed. CD was the most frequent disorder (n = 95), and had strong associations with preterm birth (47.3% of all cases with CD) and intrauterine fetal demise. VUE (n = 74) was exclusively diagnosed in the third trimester. This disorder was associated with a birth weight below the 10th percentile (45% of the cases) and hypertensive disease in pregnancy. Miscarriage and intrauterine fetal demise were associated with CHI (in 66.7% of cases, n = 18). Conclusions Chronic inflammatory disorders are frequently observed and contribute to major obstetric and perinatal complications. Further studies are needed to get a better picture of the connection between adverse obstetric outcomes and chronic inflammation to aid in the better counseling of patients.
Purpose Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. Methods Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. Results 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI − 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference − 114.34 [− 122.97; − 105.71]) and RH (mean difference − 287.14 [− 392.99; − 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference − 3.06 [− 3.28; − 2.83]) and RH (mean difference − 3.77 [− 5.10; − 2.44]) compared to AH. Conclusion Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.
Flow diagram of the systematic review and meta-analysis: search and study selection
Forest plot of diagnostic odds ratio (DOR) of all 27 studies
a Forest plot of diagnostic odds ratio (DOR) of all 21 studies including women with unknown ovarian reserve before being included in the pooled studies. b Forest plot of diagnostic odds ratio (DOR) of all six studies including women with low ovarian reserve before being included in the pooled studies. c Forest plot of diagnostic odds ratio (DOR) of six studies including women with younger age before being included in the pooled studies. D Forest plot of diagnostic odds ratio (DOR) of ten studies including women with advanced age before being included in the pooled studies
Hierarchical summary receiver operating characteristic curve (HSROC) of AMH in the prediction of live birth after IVF/ICSI with 95% confidence region, 95% prediction region and diagonal line of no discrimination. a Women with unknown ovarian reserve. b Women with low ovarian reserve. c Women with younger age. d Women with advanced age
Purpose To update the evidence of anti–müllerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age. Methods PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS–2 checklist was employed to assess the quality of the included studies. Results We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89–2.59), and 2.49 (95% CI 1.26–4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87–2.60). For younger women, the DOR was 1.41 (95% CI 0.99–2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity. Conclusions This study revealed that AMH had better prediction for live birth in advanced–age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.
Purpose Cirrhosis is a diffuse pathology characterized by fibrosis of the liver and is the last stage of chronic liver diseases. It is a serious medical condition which seriously impacts reproduction and reproductive life span. The aim of this study is to evaluate the outcomes of pregnancies complicated with liver cirrhosis. Methods Retrospective chart review of the fetal and maternal results of 20 pregnant women with liver cirrhosis who had undergone antenatal follow-up and delivery at a tertiary center in a 12-year period was performed. Results Chronic hepatitis B was found to be the leading cause of liver cirrhosis in the study group, with a rate of 25% (n: 5/20). The average MELD score was calculated as 8.8 ± 3.5. Only three patients developed hepatic decompensation during pregnancy. Fetal demise was observed in 10% of the cases (n: 2/20, MELD scores 8 and 17). MELD score was significantly higher in the patients with adverse perinatal outcomes. Conclusion Even though pregnancy is rarely observed in women with liver cirrhosis, many patients are able to achieve favorable maternal and fetal results without developing hepatic decompensation with appropriate management and close follow-up. The Model for End-Stage Liver Disease (MELD) score is a clinical tool utilized to estimate the severity and survival for chronic liver disease and was previously found to be associated with unfavorable outcomes in pregnant patients. Our study confirms this finding with the current experience from a tertiary care center.
Aims The various diagnostic criteria for polycystic ovary syndrome (PCOS) raised problem for PCOS research worldwide. PCOS has been demonstrated to be significantly associated with immune response. We aimed to identify several immune-related biomarkers and construct a nomogram model for diagnosis in PCOS. Methods The mRNA expression data were downloaded from Gene Expression Omnibus (GEO) database. Significant immune-related genes were identified to be the biomarkers for the diagnosis of PCOS using random forest model (RF), support vector machine model (SVM) and generalized linear model (GLM). The key biomarkers were selected from the optimal model and were utilized to construct a diagnostic nomogram. Receiver operating characteristic (ROC) curves was used to evaluate diagnostic ability of nomogram. Moreover, the relative proportion of 22 immune cell types was calculated by CIBERSORT algorithm. Results Four immune-related biomarkers (cAMP, S100A9, TLR8 and IL6R) were demonstrated to be highly expressed in PCOS. The nomogram constructed on the ground of the four key biomarkers showed perfect performance in diagnosis of PCOS, whose AUC were greater than 0.7. Higher infiltrating abundance of neutrophils, resting NK cells and activated dendritic cells were observed in PCOS and were tightly associated with the four key biomarkers. Conclusions This study identified several immune-related diagnostic biomarkers for PCOS patients. The diagnostic nomogram constructed based the biomarkers provide a theory foundation for clinical application. Multiple immune cells were associated with the expression of these four biomarkers and might played a vital role in the procession of PCOS.
Overall prevalence of different HPV genotypes
Proportion of single and multiple infections of HPV in the HPV-positive groups according to age
High-risk HPV subtype infection frequency
Low-risk HPV subtype infection frequency
Purpose Human papillomavirus (HPV) infection, especially high-risk HPV, is a major etiological factor for cervical cancer. This study aimed to investigate the distribution of human papillomavirus infection among female outpatients in Northeast China. Methods A total of 110,927 women aged between 18 and 80 years from Shengjing Hospital of China Medical University, tested with the HPV Geno-Array Test Kit (HybriBio), were enrolled in this study. Results The overall prevalence of HPV infection in the study population was 16.95% (18,802/110,927). A total of 21 HPV genotypes were identified and the six most prevalent ones were HPV16 (5.78%), HPV58 (2.62%), HPV52 (1.91%), HPV33 (1.55%), HPV53 (1.45%), and HPV18 (1.16%). The prevalence of single HPV was 83.58% (15,714/18802) and that of multiple HPV was 16.42% (3088/18802). HPV16, HPV58, and HPV52 were the most common types of HR-HPV infections, while CP8304, HPV11, and HPV6 were the most common types of LR-HPV infections. Among the multiple infection groups, HPV16 was the most common type of co-infection. Furthermore, the prevalence of HPV infections varied among different age groups. Age-specific prevalence of HPV exhibited two peaks in the youngest age group and in the group aged 50–60 years. Conclusion HPV16, 58, 52, 33, 53, and 18 were the most common types in the general female population. The prevalence of HPV infection varied among different age groups. This study provides guidance for future HPV-based cervical cancer screening tests and prophylactic HPV vaccinations in China.
FIGO leiomyoma subclassification system. Reprinted from Ref. [15].
Copyright 2011. with permission, from Ref. [12]. ((Licensed Content Publisher: John Wiley and Sons—Licensed Content Autor: Malcom G. Munro. Granted Licensed Number: 52129990134061))
Transient occlusion of the uterine artery on the right side with straight 11 mm Yasargil® clip (FE769K; Aesculap)
Transient occlusion of the uterine artery on the right side with curved 13.8 mm Yasargil® clips (FE783K; Aesculap)
Vascular clip is inserted through the 10-mm trocar, is opened by an alligator forceps and placed over the uterine artery
Reconstruction of the uterine wall with interrupted intracorporal double-layer sutures
Objectives The goal of this study was to examine the safety, feasibility, and effectiveness of the use of a microsurgical temporary vascular clip system to facilitate the laparoscopic enucleation of very large intramural uterine fibroids. Methods In this retrospective study, the surgical outcomes of 26 patients who underwent laparoscopic myomectomy with temporary uterine vessel clipping for very large (the largest measured diameter ≥ 9 cm) symptomatic intramural uterine fibroids in two tertiary referral hospitals between September 2017 and March 2020 were examined. Titan-made vascular clips (YASARGIL® Aneurysm Clip System) were used to temporarily occlude the bilateral uterine arteries and utero-ovarian vessels. Main outcomes included operating time, blood loss, number of leiomyomas and weight, conversion rate, intra- and postoperative complication rates, and length of hospital stay. Results Twenty six patients were included. Dominant intramural uterine fibroid diameters were 9–22 cm. The general characteristics of the patients were similar. The mean surgery duration and intraoperative blood loss were 175.3 ± 32.7 (range 120–250) min and 241.1 ± 103 (range 100–450) ml, respectively. The median postoperative drop in hemoglobin was 0.89 ± 0.75 g/dL. No patient required blood transfusion. No procedure was converted to laparotomy. No major intra- or postoperative complication occurred. Conclusions Laparoscopic myomectomy for very large intramural uterine fibroids can be performed safely and effectively, with less intraoperative blood loss, using vascular clips for temporary clamping of the bilateral uterine vessels.
Top-cited authors
Eyal Sheiner
  • Ben-Gurion University of the Negev
Antonio Simone Laganà
  • Università degli Studi di Palermo
Salvatore Giovanni Vitale
  • University of Catania
Markus Wallwiener
  • Universität Heidelberg
Ruslan Sergienko
  • Ben-Gurion University of the Negev