Rate of Involved Endocervical Margins According to High-Risk Human Papillomavirus Subtype and Transformation Zone Type in Specimens with Cone Length ≤ 10 mm versus > 10 mm-A Retrospective Analysis.

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013-2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ.

HPV screening in the urine of transpeople - A prevalence study.

Background: There is limited data on human papillomaviruses (HPV) prevalence in transpeople due to low acceptance rate of screening methods. HPV tests from self-collected urine are gender-neutral, have a high acceptance, and have a comparable accuracy in females to clinician-collected samples. The aim of this study was to evaluate both the HPV prevalence in the urine in a large cohort of 200 transpeople with common risk profiles and the acceptability of such screening method. Methods: The study was conducted at the outpatient clinic for transpeople at the Department of Obstetrics and Gynaecology, Medical University of Vienna, Austria. 200 transpeople have been enrolled between May and October 2021. Inclusion criteria were gender identity dysphoria, age over 18 years, and adequate language skills.Subjects were asked to answer a survey concerning gender identity, established risk factors for HPV infections as well as their preference regarding urine or provider-collected cytology-/HPV-based screening, and to provide a urine sample. Five patients not able to provide urine were excluded. HPV genotyping was performed using a validated multiplex real-time PCR assay, which simultaneously detects 28 HPV genotypes. This trial is registered at ClinicalTrials.gov, NCT04864951. Findings: Overall HPV positivity was 19·0% (37/195), 24·2% in female to male, 11·8% in male to female, 26·3% in genderqueer/non binary/other subjects, 27·9% in subjects currently having a cervix, and 26·0% in subjects born with cervix. Independent of gender reassignment surgery, being born with a cervix was associated with a higher risk of HPV infections (p = 0·008), yet 42·3% (44/104) have never attended cervical cancer screening. Overall, 79·0% (154/195) of transpeople would prefer urine HPV tests to provider-collected HPV screening. Interpretation: HPV testing in self-collected urine samples provides a unique opportunity for screening of this hard-to-reach population and should be evaluated in further studies. Funding: None.

Effect of Viewing Disney Movies During Chemotherapy on Self-Reported Quality of Life Among Patients With Gynecologic Cancer: A Randomized Clinical Trial.

Importance: In addition to treatment efficacy, evaluation of adverse effects and quality of life assessments have become increasingly relevant in oncology. Objective: To evaluate the association of watching Disney movies during chemotherapy with emotional and social functioning and fatigue status. Design, Setting, and Participants: This randomized clinical trial was performed from December 2017 to December 2018 at a cancer referral center in Vienna, Austria. A consecutive sample of women with gynecologic cancers was recruited through July 2018. Inclusion criteria included age older than 18 years, written informed consent, and planned 6 cycles of chemotherapy with either carboplatin and paclitaxel or carboplatin and pegylated liposomal doxorubicin. Exclusion criteria were inadequate knowledge of the German language or receipt of other chemotherapy regimens. Data analysis was performed from February 2019 to April 2019. Intervention: Participants were either shown Disney movies or not during 6 cycles of chemotherapy. Before and after every cycle, they completed standardized questionnaires from the European Organisation for Research and Treatment of Cancer (EORTC). Main Outcomes and Measures: Primary outcomes were change of quality of life, as defined by the EORTC Core-30 (version 3) questionnaire, and fatigue, as defined by the EORTC Quality of Life Questionnaire Fatigue, during 6 cycles of chemotherapy. Results: Fifty-six women entered the study, and 50 completed it, including 25 women in the Disney group (mean [SD] age, 59 [12] years) and 25 women in the control group (mean [SD] age, 62 [8] years). In the course of 6 cycles of chemotherapy, patients in the Disney group felt less tense and worried less than patients in the control group according to their responses to the questions about emotional functioning (mean [SD] score, 86.9 [14.3] vs 66.3 [27.2]; maximum test P = .02). Furthermore, watching Disney movies was associated with less encroachment on patients' family life and social activities, as evaluated by the social functioning questions (mean [SD] score, 86.1 [23.0] vs 63.6 [33.6]; maximum test P = .01). Moreover, this intervention led to fewer fatigue symptoms (mean [SD] score, 85.5 [13.6] vs 66.4 [22.5]; maximum test P = .01). Perceived global health status was not associated with watching Disney movies (mean [SD] score, 75.9 [17.6] vs 61.0 [25.1]; maximum test P = .16). Conclusions and Relevance: These findings suggest that watching Disney movies during chemotherapy may be associated with improvements in emotional functioning, social functioning, and fatigue status in patients with gynecologic cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03863912.

Prevalence of Gestational Diabetes in Triplet Pregnancies: A Retrospective Cohort Study and Meta-Analysis.

BACKGROUND: Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). The literature on GDM rates in triplet pregnancies is scarce. METHODS: A retrospective cohort study was performed to assess the prevalence of GDM in women with a triplet pregnancy. GDM was defined through an abnormal oral glucose tolerance test (OGTT). A meta-analysis of GDM prevalence was also carried out. RESULTS: A cohort of 60 women was included in the analysis. Of these, 19 (31.7%) were diagnosed with GDM. There were no differences in pregnancy outcomes between women with and without GDM. In the meta-analysis of 12 studies, which used a sound GDM definition, an estimated pooled prevalence of 12.4% (95% confidence interval: 6.9%-19.1%) was found. In a leave-one-out sensitivity analysis, the estimated GDM prevalence ranged from 10.7% to 14.1%. CONCLUSION: The rate of GDM seems increased in women with triplets compared to singleton pregnancies. However, GDM did not impact short-term pregnancy outcomes.

The impact of p16ink4a positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study.

PURPOSE: To evaluate HPV and p16ink4a status as prognostic factors in patients with invasive vulvar cancer. METHODS: Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16ink4a status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16ink4a positivity. RESULTS: 135 patients were included in the analysis. 32 (23.7%) showed a p16ink4a expression of over 25%. Disease-free and disease-specific survival was longer in p16ink4a positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16ink4a positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. CONCLUSIONS: Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16ink4a positive invasive vulvar cancer.

Prognostic Laboratory Parameters in Placental Abruption: A Retrospective Case-Control Study.

To evaluate routine laboratory parameters in women with and without placental abruption (PA) and in controls, 417 women were included in this retrospective cohort study in a tertiary-care center. 118 women with PA (Group A: 54 without vaginal bleeding and Group B: 64 with bleeding), 130 women without either PA or vaginal bleeding throughout their pregnancy (Group C), 123 women with vaginal bleeding but without PA (Group D), and 46 healthy pregnant women who had undergone a control laboratory evaluation in the second/third trimester for history of previous cytomegalovirus (additional control group) were included. Hemoglobin, leukocytes, thrombocytes, C-reactive protein (CRP), and fibrinogen were obtained within 48 hours before C-section and/or at the time of bleeding onset. Cases (Groups A and B) revealed higher CRP levels than controls (Groups C and D) after multivariate analysis in the sub-analyses of bleeding (0.56 mg/dL, interquartile range (IQR) 0.28­1.24 vs. 0.51 mg/dL, IQR 0.28­0.84; odds ratio (OR) 1.108, p = 0.006) and non-bleeding women (0.64 mg/dL, IQR 0.48­1.08 vs. 0.32 mg/dL, IQR 0.18­0.61; OR 7.454, p < 0.001). The non-bleeding cases (Group A) revealed significantly higher leukocyte (12.01 g/L, IQR 9.41­14.10 vs. 9.21 g/L, IQR 7.95­10.49; OR 1.378, 95% confidence interval (CI): 1.095⁻1.735; p = 0.006) and CRP levels (0.64 mg/dL, IQR 0.48­1.08 vs. 0.33 mg/dL, IQR 0.20­0.50; OR 7.942, 95% CI: 1.435­43.958; p = 0.018) than the additional control group. In cases, none of the laboratory parameters differed between women with and without bleeding. The significantly increased CRP levels found for women with PA and the lack of a difference in CRP between bleeding and non-bleeding cases point toward a chronic process underlying placental abruption. However, this laboratory parameter does not seem clinically relevant for distinguishing between women with and without placental abruption at this point in time.

Risk-adapted management for vasa praevia: a retrospective study about individualized timing of caesarean section.

PURPOSE: Vasa praevia is a rare condition with high foetal mortality if not detected prenatally. There is limited evidence available to determine the ideal timing of delivery and management recommendations. The aim of this study was to critically review our experience with vasa praevia, with a focus on diagnosis and management. METHODS: In a retrospective analysis, all cases of vasa praevia identified in our department from January 2003 to December 2017 were included. All cases were diagnosed antenatally during sonographic inspection of the placenta, and individualized management for each patient was performed based on individual risk factors. 19 cases of vasa praevia were identified (15 singletons, four twins). 13 patients (79%) presented placental anomalies. In patients at high risk for preterm birth, caesarean delivery was performed between 34-35 weeks after early hospitalization and administration of corticosteroids, whereas in patients at low risk for preterm birth, caesarean section could be delayed to 35-37 weeks of gestation. Administration of corticosteroids was not obligatory in the latter cases. RESULTS: There were two acute caesarean sections, due to premature abruption of the placenta and vaginal bleeding. There was no maternal or foetal/neonatal death. None of the neonates required blood transfusion. There is limited evidence available with which to determine the ideal timing of delivery. CONCLUSION: However, our individualized, risk-adapted management, which attempts to delay the timing of caesarean section up to two weeks beyond the standard recommendation, seems feasible, with just two emergency caesarean sections and no case of foetal or maternal death.

Heavy black tea consumption and elevated CA 19-9 and CA 125 levels. A case report on a patient with ovarian endometriotic cysts.

In this case report, we present a case of false positive CA 19-9 and CA 125 levels in a patient with suspected endometriotic cysts. The patient is a 34-year-old nulliparous woman with heavy black tea consumption and elevated CA 19-9 and CA 125 levels. After discontinuation of black tea intake and careful exploration of other possible factors, CA 19-9 and CA 125 levels dropped markedly. As a conclusion, heavy black tea consumption can lead to false positive results of elevated CA 19-9 and CA 125 levels.

Does anti-Mullerian hormone predict the outcome of further pregnancies in idiopathic recurrent miscarriage? A retrospective cohort study.

PURPOSE: To evaluate whether anti-Mullerian hormone, basal follicle-stimulating hormone, luteinizing hormone, estradiol, and female age would predict future outcomes in women with idiopathic recurrent miscarriage. METHODS: One hundred and sixteen women with idiopathic recurrent miscarriage were retrospectively included. Luteal support with or without a combined treatment regimen for idiopathic recurrent miscarriage was applied in a tertiary-care center in Vienna. Occurrence and outcome of further pregnancies were analyzed. RESULTS: Within a median follow-up duration of 42.3 months, 94 women (81.0%) achieved one or more pregnancies. Further miscarriages occurred in 47 patients in whom only a higher number of previous miscarriages was predictive (OR 3.568, 95% CI 1.457-8.738; p = 0.005). Fifty-seven women had a live birth > 23 + 0 gestational weeks. In a multivariate analysis, age (OR 0.920, 95% CI 0.859-0.986; p = 0.019) and the number of previous miscarriages (OR 0.403, 95% CI 0.193-0.841; p = 0.016), but not AMH (OR 1.191, 95% CI 0.972-1.461; p = 0.091) were significantly predictive. CONCLUSION: AMH seems of either no or only minor relevance for the prediction of further miscarriages and live birth in women with idiopathic recurrent miscarriage.

Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia.

Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE). Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE. In contrast to published literature, we demonstrate that placenta-associated diamine oxidase (DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels. Cultures of primary EVTs express and secret large amounts of bioactive DAO. ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs. Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels. This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.

Reliability of sonographic fetal weight estimation in triplet pregnancies: a retrospective cohort study.

PURPOSE: To review our experience in ultrasound fetal weight estimation in our large population of triplet pregnancies. METHODS: Ninety-seven triplet pregnancies were retrospectively included between January 2003 and January 2017. Sonographic fetal weight estimation using Hadlock's and Schild's formulas was compared to actual birth weight in a tertiary-care center in Vienna, Austria. Statistical analyses were performed using a stepwise linear regression model and crosstabs. RESULTS: The median discrepancy between the sonographically estimated fetal weight by Hadlock's formula and the actual birth weight was 106 g (IQR 56-190). The percentage error and its standard deviation were - 2.5 ± 12.1%, and the median percentage error was - 3.6%. Concerning the use of Hadlock's formula, estimated fetal weight was the most important factor predictive of actual birth weight with an estimate of 0.920 (p < 0.001). Female neonates had been overestimated by a mean of 50.473 g per fetus. The sonographic prediction of small-for-gestational-age neonates was significantly reliable (p < 0.001), with positive and negative predictive values ranging from 81.3 to 100.0%. Similar results were obtained for Schild's formula. CONCLUSION: Even if sonographically estimated fetal weight in triplet pregnancies has a high overall accuracy of fetal weight estimation, there are some limitations in prediction of intrauterine growth restrictions, especially in female fetuses.

Fetal Survival in Second-Trimester Termination of Pregnancy Without Feticide.

OBJECTIVE: To evaluate the rate of live birth and the duration of survival after termination of pregnancy without feticide. METHODS: We conducted a retrospective analysis of 241 terminations of pregnancy without feticide for fetal anomalies or genetic abnormalities between 20 0/7 and 24 0/7 weeks of gestation at a single tertiary care referral center in Europe between February 2003 and May 2017. A multivariate binary regression model was used to evaluate factors associated with live birth. RESULTS: Pregnancies were terminated at a mean gestational age of 22.1±1.1 completed weeks of gestation. Median birth weight was 440 g (range 141-1,890 g). Live birth occurred in 122 cases (50.6%, 95% CI 44.4-56.8); median survival time was 32 minutes (range 1-267 minutes). Factors associated with live birth were gestational age at labor induction (odds ratio 1.41, 95% CI 1.01-2.01; P=.049) and fetal anomalies (P=.046). CONCLUSION: After termination of pregnancy without feticide between 20 0/7 and 24 0/7 weeks of gestation, the live birth rate was 50.6% (95% CI 44.4-56.8). A lower gestational age at labor induction and the presence of skeletal, cerebral, renal, or multiple fetal anomalies increased the chance of stillbirth.

Oligomannosidic glycans at Asn-110 are essential for secretion of human diamine oxidase.

N-Glycosylation plays a fundamental role in many biological processes. Human diamine oxidase (hDAO), required for histamine catabolism, has multiple N-glycosylation sites, but their roles, for example in DAO secretion, are unclear. We recently reported that the N-glycosylation sites Asn-168, Asn-538, and Asn-745 in recombinant hDAO (rhDAO) carry complex-type glycans, whereas Asn-110 carries only mammalian-atypical oligomannosidic glycans. Here, we show that Asn-110 in native hDAO from amniotic fluid and Caco-2 cells, DAO from porcine kidneys, and rhDAO produced in two different HEK293 cell lines is also consistently occupied by oligomannosidic glycans. Glycans at Asn-168 were predominantly sialylated with bi- to tetra-antennary branches, and Asn-538 and Asn-745 had similar complex-type glycans with some tissue- and cell line-specific variations. The related copper-containing amine oxidase human vascular adhesion protein-1 also exclusively displayed high-mannose glycosylation at Asn-137. X-ray structures revealed that the residues adjacent to Asn-110 and Asn-137 form a highly conserved hydrophobic cleft interacting with the core trisaccharide. Asn-110 replacement with Gln completely abrogated rhDAO secretion and caused retention in the endoplasmic reticulum. Mutations of Asn-168, Asn-538, and Asn-745 reduced rhDAO secretion by 13, 71, and 32%, respectively. Asn-538/745 double and Asn-168/538/745 triple substitutions reduced rhDAO secretion by 85 and 94%. Because of their locations in the DAO structure, Asn-538 and Asn-745 glycosylations might be important for efficient DAO dimer formation. These functional results are reflected in the high evolutionary conservation of all four glycosylation sites. Human DAO is abundant only in the gastrointestinal tract, kidney, and placenta, and glycosylation seems essential for reaching high enzyme expression levels in these tissues.

Intra- versus retroplacental hematomas: a retrospective case-control study on pregnancy outcomes.

BACKGROUND: Intrauterine hematomas are a common pregnancy complication. The literature lacks studies about outcomes based on hematoma localization. Thus, we aimed to compare pregnancies complicated by an intraplacental hematoma to cases with a retroplacental hematoma and to a control group. METHODS: In a retrospective case-control study, 32 women with an intraplacental hematoma, 199 women with a retroplacental hematoma, and a control group consisting of 113 age-matched women with no signs of placental abnormalities were included. Main outcome measures were pregnancy complications. RESULTS: Second-trimester miscarriage was most common in the intraplacental hematoma group (9.4%), followed by women with a retroplacental hematoma (4.2%), and controls (0%; p = 0.007). The intraplacental hematoma group revealed the highest rates for placental insufficiency, intrauterine growth retardation, premature preterm rupture of membranes, preterm labor, preterm delivery <37 weeks, and early preterm delivery <34 weeks (p < 0.05), followed by the retroplacental hematoma group. When tested in multivariate models, intraplacental hematomas were independent predictors for placental insufficiency (ß = 4.19, p < 0.001) and intrauterine growth restriction (ß = 1.44, p = 0.035). Intrauterine fetal deaths occurred only in women with a retroplacental hematoma (p = 0.042). CONCLUSIONS: Intra- and retroplacental hematomas have different risk profiles for the affected pregnancy and act as independent risk factors.

HPV prevalence in vulvar cancer in Austria.

BACKGROUND: Even if vulvar cancer is not common, over one hundred women are affected in Austria per year. There is strong evidence that basaloid and warty variants are associated with types of human papillomavirus (HPV). METHODS: The aim of this study is to analyze the types of HPV in vulvar cancer in Austria. This cross-sectional period-prevalence international collaborative study on archival specimens was performed in cooperation with the Institut Catalan di Oncologia in Barcelona, Spain. A total of 177 consecutive samples of Austrian women were analyzed to detect the presence of various HPV types using the SPF10 PCR/DEIA/LiPA25 system. Furthermore, the expression of the tumor suppressor protein p16INK4a was analyzed by immunohistochemistry (CINtec histology kit, ROCHE). A tumor was considered HPV-driven if an overexpression of p16INK4a was detected. RESULTS: In all, 41 cases of vulvar cancer tested positive for HPV DNA (23%) and 32 (18%) were p16 positive. Patients with warty and basaloid squamous cell cancer were significantly younger than those with keratinizing squamous cell cancer (63.3 years vs. 71.0 years, p = 0.021). In addition, 77.4% of all cases suffering from warty or basaloid squamous cell cancer tested positive for HPV, compared to 9.5% of the keratinizing squamous cell cancer cases (p < 0.001). The most commonly detected HPV strain was type 16, followed by 31 and 33. CONCLUSION: Infection with HPV type 16 appears to be strongly correlated to the development of warty or basaloid squamous cell cancer. Vaccination against HPV can be expected to prevent this type of vulvar cancer.

Anti-Mullerian hormone is linked to the type of early pregnancy loss in idiopathic recurrent miscarriage: a retrospective cohort study.

We correlated Anti-Mullerian hormone (AMH) levels and other parameters for ovarian reserve to the gestational age at the time of pregnancy loss in women with idiopathic recurrent miscarriage. In a retrospective study, 79 patients had suffered a total of 266 miscarriages. When comparing women with an "unembryonic" to those with an "embryonic" most recent miscarriage, there was no difference in median age (36.3 years, IQR 31.6-40.1 versus 34.2 years, IQR 29.9-38.0; p = 0.303) but in median AMH levels (0.7, IQR 0.2-18, versus median 1.8, IQR 1.3-3.3, respectively, p = 0.044) and in the rate of patients with an AMH ≤ 1 ng/mL (23/37, 62.2%, versus 8/42, 19%; p < 0.001). Thus, AMH might add to the diagnostic process in recurrent miscarriage in the future.

Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials.

BACKGROUND: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody responses was assessed. METHODS: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. RESULTS: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1. CONCLUSIONS: 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination.

Cervical length dynamics in triplet pregnancies: a retrospective cohort study.

PURPOSE: To review our experience with a screening program that included sequential cervical length measurements in our large population of triplet pregnancies. METHODS: Seventy-eight triplet pregnancies were retrospectively included. Cervical length measurements were performed by transvaginal ultrasound in 2-week intervals from week 16 + 0 onwards in a tertiary-care center in Vienna. The main outcome measurement was preterm delivery prior to 32 + 0 weeks of gestation. Statistical analyses were performed using paired and unpaired t tests and a stepwise linear regression model. RESULTS: There were 26 cases of preterm delivery (33.3%). Women with preterm delivery revealed significant cervical length shortening from week 22 + 0 (median 33 mm, interquartile range, IQR 17-39) to 24 + 0 (median 21 mm, IQR 7-30; p = 0.005). This was not observed in women without preterm delivery. From week 22 + 0 onwards, both groups showed further significant 2-week differences in cervical length (p < 0.05). Univariate analysis of cervical length in weeks 20 + 0, 22 + 0, and 24 + 0 as well as cervical length dynamics from 22 + 0 to 24 + 0 predicted preterm delivery. CONCLUSIONS: In triplet pregnancies, a decrease in cervical length seems physiological from week 22 + 0 onwards. A sharp decrease in cervical length from the 22 + 0 to the 24 + 0 week as well as the smaller cervical length in weeks 20 + 0, 22 + 0, and 24 + 0 increase the risk of preterm delivery.

Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions.

STUDY QUESTION: Do extravillous trophoblasts (EVTs) invade non-arterial decidual vessels in healthy and pathological pregnancies? SUMMARY ANSWER: Our results reveal that trophoblast invasion of venous and lymphatic vessels is a frequent event during the first trimester of pregnancy and is compromised in  recurrent spontaneous abortion (RSA). In addition, the present data suggest that EVTs populate regional lymph nodes during pregnancy. WHAT IS ALREADY KNOWN: Human trophoblasts remodel and invade decidual spiral arteries. In addition, a recent report demonstrates that trophoblasts contact and invade decidual veins. STUDY DESIGN, SIZE, DURATION: Tissue samples of human first trimester deciduae basalis (n = 54, 6th-13th weeks of gestation) obtained from elective pregnancy terminations were used to study trophoblast invasion into veins and lymphatics, in comparison to arteries. Age-matched cases of idiopathic, recurrent spontaneous abortions tissue samples (n = 23) were assessed for cell numbers of EVTs in these decidual vessels. In addition, lymph nodes of four pregnant women were analysed for the presence of EVTs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Localization, frequency and EVT-mediated targeting and invasion of arterial, venous as well as lymphatic vessels were determined in first trimester decidua basalis tissue sections using immunofluorescence staining with antibodies against CD31, CD34, ephrin B2 (EFNB2), ephrin receptor B4 (EPHB4), HLA-G, podoplanin, prospero-related homeobox 1 (Prox-1), alpha-smooth muscle actin 2 (ATCTA2), von willebrand factor (vWF) and proteoglycan 2 (PRG2). Arterial, venous and lymphatic-associated EVTs were further characterized according to their position in the vascular structure and classified as intramural (im) or intraluminal (il). MAIN RESULTS AND THE ROLE OF CHANCE: EVTs, specifically expressing PRG2, target and invade veins and lymphatics in first trimester decidua basalis since HLA-G+ trophoblast were detected in the vascular wall (intramural EVT, imEVTs) and in the lumen of these vessels (intraluminal EVT, ilEVTs). In total, 276 arteries, 793 veins and 113 lymphatics were analysed. While EVTs contact and invade arteries and veins to a similar extent we found that lymphatics are significantly less affected by EVTs (P = 0.001). Moreover, ilEVTs were detected in the lumen of venous and lymphatic vessels, whereas ilEVTs were only found occasionally in the lumen of arteries. Interestingly, RSA tissue sections contained significantly more arterial (P = 0.037), venous (P = 0.002) and lymphatic vessels (P < 0.001), compared to healthy controls. However, while RSA-associated arterial remodeling was unchanged (P = 0.39) the ratios of EVT-affected versus total number of veins (P = 0.039) and lymphatics (P < 0.001) were significantly lower in RSA compared to age-matched healthy decidual sections. Finally, HLA-G+/PRG2+/CD45-EVTs can be detected in regional lymph nodes of pregnant women diagnosed with cervical cancer. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, first trimester decidual tissues from elective terminations of pregnancies have been examined and used as a reference for healthy pregnancy. However, this collective may also include pregnancies which would have developed placental disorders later in gestation. Due to limitations in tissue availability our staining results for EVT-specific marker expression in regional lymph nodes of pregnant women are based on four cases only. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we propose migration of HLA-G+ cells into regional lymph nodes during pregnancy suggesting that the human EVT is capable of infiltrating maternal tissues via the blood stream. Moreover, the description of compromised EVT invasion into the venous and lymphatic vasculature in RSA may help to better understand the pathological characteristics of idiopathic recurrent pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Austrian Science Fund (grant P-25187-B13 to J.P. and grant P-28417-B30 to M.K.). There are no competing interests to declare.