Safety of non-steroidal anti-inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure when administered for postpartum analgesia in women with hypertensive disorders of pregnancy. METHODS: MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were searched systematically from inception to 5 December 2019 for studies evaluating the safety of postpartum NSAIDs in women with any gestational hypertensive disorder. Randomized controlled trials (RCTs) and cohort studies were eligible for inclusion. Case-control studies, case series and case reports were excluded. The primary outcomes of interest were the incidence of severe hypertension and systolic, diastolic and mean arterial blood pressure. Pooled estimates were obtained by fitting a random-effects statistical model. The quality of evidence was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: Ten studies were included, comprising five RCTs and five retrospective cohort studies and involving a total of 1647 women. All studies were evaluated qualitatively and eight of them were included in the quantitative meta-analysis. Administration of NSAIDs was not associated with a significantly higher risk of severe postpartum hypertension (odds ratio, 1.52 (95% CI, 0.77-3.01)). Similarly, no significant differences were found in postpartum systolic blood pressure (mean difference (MD), -3.03 mmHg (95% CI, -6.21 to 0.15 mmHg)) and mean arterial pressure (MD, -0.38 mmHg (95% CI, -1.88 to 1.11 mmHg)) between women who received NSAIDs and those who did not, whereas postpartum diastolic blood pressure was marginally lower in women treated with NSAIDs (MD, -2.28 mmHg (95% CI, -4.44 to -0.13 mmHg)). The same effects were observed when studies with a large sample size, RCTs, women with severe pre-eclampsia and studies using ibuprofen as the study drug and acetaminophen as the control treatment were examined separately. The credibility of evidence was judged to be very low according to GRADE, owing to concerns about study limitations, inconsistency and imprecision. CONCLUSIONS: This meta-analysis suggests that postpartum administration of NSAIDs is not associated with elevated blood pressure in women with hypertensive disorders of pregnancy. However, the existing evidence is of very low quality, thus future large-scale RCTs are warranted to verify the safety of postpartum NSAIDs in this population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Agenesis of ductus venosus in sequential first and second trimester screening.

OBJECTIVE: The goal of this study is to evaluate the potential of first trimester (FT) screening in the diagnosis of agenesis of the ductus venosus (ADV) and to study its prevalence in a low-risk population, the associated conditions, and pregnancy outcome. METHOD: Prospective, sequential screening study at two tertiary units with morpho-functional evaluation of the ductus venosus during the first and second trimester screening. We quantified the FT detection rate, prevalence, and associated conditions: umbilical shunting type, concomitant anomalies, and outcome. RESULTS: In 6114 consecutive pregnancies, we identified 11 cases of ADV. Ten (91%) were identified during the FT examination. The prevalence was 1 in 556, similar for both centers (1/478 vs. 1/691). Major structural defects and fetal effusions were detected in 8 (73%). twenty two percent had a major chromosomal abnormality. In 3 cases, the anomaly was isolated and had normal outcome, independent of liver by-pass, caliber of the shunt, and NT thickness. CONCLUSIONS: Agenesis of the ductus venosus can be detected during FT. The early detection of ADV is important given its high association with major abnormalities.

Improved detection rate of structural abnormalities in the first trimester using an extended examination protocol.

OBJECTIVE: To assess the potential of first-trimester sonography in the detection of fetal abnormalities using an extended protocol that is achievable with reasonable resources of time, personnel and ultrasound equipment. METHODS: This was a prospective two-center 2-year study of 5472 consecutive unselected pregnant women examined at 12 to 13 + 6 gestational weeks. Women were examined using an extended morphogenetic ultrasound protocol that, in addition to the basic evaluation, involved a color Doppler cardiac sweep and identification of early contingent markers for major abnormalities. RESULTS: The prevalence of lethal and severe malformations was 1.39%. The first-trimester scan identified 40.6% of the cases detected overall and 76.3% of major structural defects. The first-trimester detection rate (DR) for major congenital heart disease (either isolated or associated with extracardiac abnormalities) was 90% and that for major central nervous system anomalies was 69.5%. In fetuses with increased nuchal translucency (NT), the first-trimester DR for major anomalies was 96%, and in fetuses with normal NT it was 66.7%. Most (67.1%) cases with major abnormalities presented with normal NT. CONCLUSIONS: A detailed first-trimester anomaly scan using an extended protocol is an efficient screening method to detect major fetal structural abnormalities in low-risk pregnancies. It is feasible at 12 to 13 + 6 weeks with ultrasound equipment and personnel already used for routine first-trimester screening. Rate of detection of severe malformations is greater in early- than in mid-pregnancy and on postnatal evaluation. Early heart investigation could be improved by an extended protocol involving use of color Doppler.

Maternal age as a predictive factor of pre-term birth. An epidemiological study from 1999 to 2008 in Greece.

The aim of the study was to estimate the risk of pre-term birth in women giving birth in Greece in different age groups. Data about women giving birth in Greece were retrieved from the Hellenic Vital Statistics covering the years from 1999 to 2008. Relative risk using χ(2) contingency tables was estimated among maternal age groups formed. These groups included mothers < 15 years of age, 15-19, 20-34 (used as a control group) and women > 34 (35-39, 40-44, 45-49 and ≥ 50) years of age. Relative risk of each age group was compared with mothers 20-34 years of age. A total of 1,069,413 valid births were included in the study and 72,156 of them were pre-term (6.75% of total count). Results exhibit a 'U'-shaped distribution of risk. Higher risk of pre-term birth is noted in the groups of < 15 years (Pearson χ(2) = 14.964, p < 0.001, risk = 1.569, CI = 1.249-1.970) and above 34 years of age (Pearson χ(2) = 2991.26, p < 0.001, risk = 1.572, CI = 1.546-1.597). For older women, a steep rise in the relative risk for pre-term birth was noted beyond the 40-44 years of age group. Finally, of interest is the fact that 'late' pre-terms (34-36 gestational weeks) account for most of the pre-term birth in mothers beyond 34 years of age.

VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2.

BACKGROUND: Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites. METHODS: T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed. RESULTS: The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells. CONCLUSION: Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.

Regeneration of uterine cervix at 6 months after large loop excision of the transformation zone for cervical intraepithelial neoplasia.

OBJECTIVE: To sonographically investigate cervical regeneration 6 months after large loop excision of the transformation zone (LLETZ) conisation for cervical intraepithelial neoplasia (CIN) pathology. DESIGN: Prospective observational study. SETTING: University Hospital setting. POPULATION: Women having LLETZ conisation for intraepithelial lesions in response to abnormal Papanicolaou smears or colposcopic findings. METHODS: Cervical dimensions were estimated before conisation and at 6 months with three-dimensional sonography and use of vocal™ software. Cone depth was measured using a ruler before fixation, and cone volume was measured using a volumetric tube and the fluid displacement technique. Cervical regeneration was sonographically estimated. MAIN OUTCOME MEASURES: Correlation of cervical volume regeneration with percentage of initial cervical volume excised and remaining cervical tissue immediately after conisation. RESULTS: A cohort of 112 women were initially recruited over a 2-year period and 73 women presented for ultrasound follow up at 6 months. Multivariate linear regression analysis showed that for women matched for age and initial cervical volume, if cervical volume excised was increased by 1% then regeneration of tissue deficit at the cervical crater was reduced by 1.37%. There also seemed to be a cutoff point suggesting that when >14% of initial cervical volume was excised, the tissue deficit at the cervical crater at 6 months was restored by <75% and there was >25% of remaining tissue deficit. CONCLUSIONS: Cervical regeneration at 6 months after excision is dependent on the percentage of initial cervical volume excised and on the remaining cervical tissue immediately after conisation. The greater the cone and the less cervical tissue remaining, the less the degree of cervical regeneration achieved.

Three-dimensional power Doppler ultrasound for the study of cervical cancer and precancerous lesions.

OBJECTIVE: To evaluate the blood flow characteristics of the cervix in normal women and in women with cervical precancerous lesions or cervical cancer. METHODS: We studied 165 women with three-dimensional power Doppler ultrasound (3D-PDU), of whom 71 had cervical cancer, 61 had precancerous lesions and 33 were healthy controls. The cervix was manually traced in the stored volumes using 15° rotation steps and the following 3D-PDU indices were calculated: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). These indices were compared among the study groups and were also correlated with features of the precancerous lesions group and cancer group. RESULTS: The three indices were all statistically significantly higher in the cervical cancer group and precancerous lesions group than in controls (P < 0.001). In addition, significantly higher values of all indices were found in the cervical cancer group than in the precancerous lesions group (P < 0.001). Further analysis according to patient characteristics in the cancer group showed that VI, FI and VFI were not significantly different in relation to grade, histology, presence of positive lymph nodes or lymphovascular space involvement (P > 0.05). However, VI was significantly higher in patients with Stages IIIB-IV cancer than in patients with less advanced disease (P = 0.045). In the cervical cancer group there was a significant positive correlation between 3D-PDU indices and cervical volume. CONCLUSION: 3D-PDU assessment of the cervix reveals significant differences in all indices studied between women with cervical precancerous lesions or cancer and healthy women. In women with cervical cancer, an advanced stage is associated with higher VI, but 3D-PDU indices are not related to other pathological characteristics.

Safety of hormone replacement therapy in gynaecological cancer survivors.

Therapy for endometrial, ovarian and cervical cancer in young women can cause sudden onset of intense menopausal symptoms, such as hot flushes, emotional disorders and sexual dysfunction. In order to overcome these unpleasant and sometimes severe symptoms, hormone replacement therapy (HRT) has proven to be very effective. However, its safety remains controversial. We reviewed English literature and examined whether administration of HRT in this specific population is related with more recurrences and worse prognosis. Current scientific data, comprising mainly retrospective studies, suggest that recurrence rates and survival are comparable between HRT users and non-users. However, large randomised trials are missing and definitive conclusions cannot be drawn. Gynaecological cancer survivors using HRT, although they seem to have little if any risk for recurrence, should be correctly informed about the lack of strong evidence.

Prognostic factors for early-stage epithelial ovarian cancer, treated with adjuvant carboplatin/paclitaxel chemotherapy: a single institution experience.

OBJECTIVE: Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy. METHODS: Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy. RESULTS: Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p<0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%). CONCLUSIONS: Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.

Causes of infertility in men with Down syndrome.

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.

The expression of receptivity markers in the fallopian tube epithelium.

Pinopodes represent the morphological and integrins, the biomolecular markers of endometrial receptivity. We studied using scanning electron microscopy, the expression of pinopodes on tubal samples and their corresponding endometria, from 21 women of reproductive age (7 from proliferative phase, 7 from day LH +5 and 7 from day LH +7). In addition, we examined the immunohistochemical staining of integrins alpha v beta 3, alpha v beta 5 and their ligands, fibronectin (FN) and osteopontin (OPN) in the same tubal epithelium samples. Pinopodes were detected on the tubal epithelium exclusively during day LH +7, coincident with their formation in the endometrium and synchronous to alpha v beta 3 sharp increase in the oviduct epithelium, suggesting a regulation similar to the endometrium. In contrast, alpha v beta 5, FN and OPN remained unchanged during the cycle. These results show for the first time the formation of pinopodes in the tubal epithelium at the time of endometrial receptivity and correlate it with the upregulation of the intact dimmer alpha v beta 3 in the tubes.

Serum biochemical markers of brain injury.

The diagnosis and assessment of brain damage is currently based on the clinical examination and the modern neuro-imaging techniques. Electrophysiology, haemodynamic monitoring and invasive neuromonitoring constitute additional tools for monitoring of the brain function and clinical course of the patient. However, despite the substantial progress, clinical and neuro-monitoring methods are quite often not sufficient to evaluate and quantify the severity of the initial and secondary destructive processes and hence they cannot guide efficient therapeutic measures and prognosticate effectively the outcome. During the last decades, researchers and clinicians have focused on specific markers of brain cell damage to improve the diagnosis and monitoring of neurological insults. Lactate dehydrogenase, creatine kinase, neuron specific enolase, have been proposed as potential markers of brain injury. More recently, other glial markers such as the Myelin Basic Protein, the glial fibrillary acidic protein and the S-100B protein have been measured in blood and used as surrogate biochemical markers for brain injury. This review summarizes published findings on the above brain specific serum biochemical markers with emphasis on those with clinical utility.

Clinical significance of hepatitis B surface antigen in cord blood of hepatitis B e-antigen-negative chronic hepatitis B virus-infected mothers.

Vertical transmission of hepatitis B virus (HBV) infection during the perinatal period is the major cause of HBV transmission. The aim of our study was to evaluate the serological and virological profiles of HBV infection in cord blood samples obtained from HBeAg-negative chronic HBV-infected women, at delivery, and to investigate their relationship with the clinical outcome (possible transmission of HBV) in neonates receiving the currently approved passive-active immunoprophylaxis schedule. Sixteen women (32%) exhibited HBsAg positivity in the cord blood but HBV-DNA has not been detected in any of the 50 cord blood samples evaluated. We conclude that HBsAg can be transferred through the placental barrier, as with other proteins, in about one third of HBeAg-negative chronic HBV-infected pregnant women, irrespective of the maternal viral load, the mode of delivery or the placenta HBV pathology. The clinical impact of this phenomenon on the intrauterine-transplacental or perinatal transmission of HBV infection and/or passive-active immunoprophylaxis failure does not seem to be important.

Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery.

OBJECTIVE: To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD). DESIGN: Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007. SETTING: A tertiary referral centre for fetal medicine. METHODS: Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis. MAIN OUTCOME MEASURES: The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD. RESULTS: Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median=609 pg/ml, interquartile range: 445.7-782.7) compared to controls (median=322.1 pg/ml, interquartile range: 277.7-414.4), (P<0.001). IL-18 level was also significantly higher (P<0.001) in cases with positive amniotic fluid cultures (median=697.7, interquartile range: 609.0-847.2) compared to those with negative ones (median=330.9 pg/ml, interquartile range: 235.2-440.8). CONCLUSIONS: Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.

Management of a pregnancy complicated by yolk sac tumor.

BACKGROUND: The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach. CASE: A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle. CONCLUSION: In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Peritoneal implantations of papillary serous ovarian cystadenocarcinoma 13 days after initial laparoscopic treatment for a presumed benign ovarian cyst.

We report a case of a 24-year-old female who underwent laparoscopy for a presumed benign ovarian mass. Frozen sections at laparoscopy initially revealed a borderline papillary serous ovarian tumour. Final histology showed an invasive papillary serous ovarian tumor (grade 1). Subsequent staging laparotomy conducted 13 days later revealed peritoneal implantations thus upgrading the initially thought Stage Ia papillary serous ovarian tumour at laparoscopy to Stage IIc. The patient after laparotomy had an uneventful postoperative course and received six cycles of chemotherapy based on taxol and carboplatin. A short review of the literature is also presented, concerning the factors which affect the patient's prognosis in cases of unexpected ovarian malignancy found during laparoscopy that are treated with subsequent staging laparotomy.

Clinicopathological features of primary fallopian tube carcinoma: a single institution experience.

PURPOSE OF INVESTIGATION: Primary fallopian tube carcinoma (PFTC) is a rare malignancy with only few data existing on the impact of prognostic factors. METHODS: We retrospectively analyzed 26 patients. Tissue blocks were reviewed and sections were stained for vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2), c-erbB-2, estrogen (ER), and progesterone receptors (PgR). RESULTS: Reactivity for VEGF, ER, PgR, MMP-2, MMP-9, TIMP-1, TIMP-2 and c-erbB-2 was observed in 85%, 46%, 27%, 11.5%, 58%, 0%, 23% and 8% of specimens, respectively. None of the markers studied displayed prognostic significance. Regarding clinical prognostic factors, the hazard ratio (HR) for progression and death for patients with tumor residuum > 2 cm was 5.24 (p < 0.01) and 11.19 (p < 0.005), respectively. Patients with advanced stage disease had a HR of 12.55 (p < 0.05) for progression, while the HR for death was not found to be statistically significant. CONCLUSION: None of the biomarkers studied seems to influence survival. Early-stage disease and optimal debulking are associated with improved outcome.

Extrauterine pregnancy resulting from late spontaneous rupture of an unscarred gravid uterus: case report.

PURPOSE: Rupture of the unscarred grand uterus is a rare obstetric event associated with major perinatal mortality and a high incidence of maternal mortality and morbidity, particularly peripartum hysterectomy. METHODS & RESULTS: We present the case of a primigravida woman who was admitted at 38 weeks of gestation complaining of intermittent abdominal pain and vaginal bleeding. Although initial evaluation suggested that both mother and fetus were doing well, continuous assessment resulted in cesarean section due to variable decelerations and increasing abdominal pain. An unexpected abdominal pregnancy was discovered resulting from a complete uterine rupture. A healthy infant was delivered and hysterectomy was performed. CONCLUSION: Although extrauterine advanced abdominal pregnancy resulting from late uterine rupture is associated with high maternal and perinatal mortality, a high index of suspicion, close surveillance and ultrasonography can achieve good outcome for both mother and infant. We strongly believe, that this case report contributes to the insight and further knowledge of this rare pregnancy complication.

Alexithymia is positively associated with the outcome of in vitro fertilization (IVF) treatment.

The goal was to examine prospectively the relation of psychological factors to the outcome after in vitro fertilization (IVF) in a sample of Greek women. Previous studies investigating the relation of IVF outcome to anxiety and depression have yielded contradictory results; other psychological dimensions have not been studied. 81 women who followed an IVF program during a 6-mo. period were prospectively evaluated. Demographic and gynecological data were assessed and women completed questionnaires measuring anxiety, depression, narcissistic traits, over-dependency, self-esteem, hostility, and alexithymia. Multiple logistic regression analysis showed that successful IVF outcome correlated with more alexithymic characteristics and younger age. Correlation between alexithymia and successful IVF outcome is demonstrated. This might be explained by the "operational" nature of IVF techniques, to which alexithymic individuals would respond better.

Imperforate hymen with hematocolpometra combined with elevated Ca125.

In the present case, ultrasound examination ruled out the presence of hematosalpinx or other gynecological tumors. This was of great importance to the surgical intervention, especially for avoiding laparotomy. Dilatation of the vagina and uterus, due to imperforate hymen with retrograde menstruation should be considered in the differential diagnosis of abdominal pain in premenarchal girls (Fig. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.