The ethics and practice of perinatal care at the limit of viability: FIGO recommendations.

An arbitrary gestational age limit of viability cannot be set, and in clinical practice the focus should be on a periviability interval-the so-called "gray zone" of prognostic uncertainty. For cases within this interval, the most appropriate decision-making process remains debatable and periviability has emerged as one of the greatest challenges in bioethics. Universally recognized ethical principles may be interpreted differently due to socioeconomic, cultural, and religious aspects. In the case of periviability, there is considerable uncertainty over whether interventions result in a greater balance of clinical good over harm. Furthermore, the fetus or neonate is unable to exercise autonomy and the physicians and parents will act as patient surrogates. When parents and physicians disagree about the infant's best interest, a dialogue without paternalistic attitudes is essential, whereby physicians should only offer, but not recommend, perinatal interventions. Parental choice, based on thorough information, should be respected within the limits of what is medically feasible and appropriate. When disagreements between parents and physicians occur, how is consensus to be achieved? Professional guidelines can be helpful as a framework and starting point for discussion. In reality, however, guidelines only rarely draw categorical lines and in many cases remain vague and ambiguously worded. Local ethics committees can provide counseling and function as moderators during discussions, but ethics committees do not have decision precedence. Counseling assumes the most significant role in periviability discussions, taking into consideration the particular fetal and maternal characteristics, as well as parental values. Several caveats should be observed relative to counseling: message fragmentation or inconsistence should be minimized, prognosis should preferably be presented in a positive framing, and overreliance on statistics should be avoided. It is recommended that decisions regarding neonatal resuscitation in the periviability interval be made before birth and not conditional on the newborn's appearance at birth. Regardless of decision, it is important to assure pre- and postnatal coherence. The present article describes how individual physicians, centers, and countries differ in the approach to the decision to initiate or forgo intensive care in the periviability interval. It is impossible to provide a global consensus view and there can be no unifying ethical, moral, or practical strategy. Nevertheless, ethically justified, quality care comprises early involvement of the obstetric and neonatal team to enable a coherent, comprehensible, nonpaternalistic, and balanced plan of care. Ultimately, physicians will need to adjust the expectations to the local standards, local outcome data, and local neonatal support availability.

Implementation of the Robson Classification in Greece: A Retrospective Cross-Sectional Study.

Cesarean sections have become the most commonly performed operations around the world. The World Health Organization recommended the use of the Robson classification system as a universal standard to establish a joint control system in healthcare facilities. The aim of this study was to implement the Robson classification for the first time in Greece to identify trends in cesarean births and examine the groups of women who are the main contributors to the increasing rates. Moreover, the indicators for cesarean sections will be evaluated as per the Robson classification. In the sample analysis, we included the records of 8572 women giving birth in one private health facility in Greece. A total of 8572 women gave birth during the study period, of which 5224 (60.9%) were cesarean section births and 3348 (39.1%) were vaginal births. In our study, according to the Robson classification, the largest contributors to the overall CS rate were as follows: (a) nulliparous women with a single cephalic term pregnancy, who were either labor induced or delivered by cesarean section before labor-Group 2 (34.6%); (b) multiparous women with a single cephalic term pregnancy and at least one previous cesarean section-Group 5 (30.7%); (c) women with a single cephalic preterm pregnancy-Group 10 (11.7%); (d) women with multiple pregnancies-Group 8 (7.0%). Our study is expected to assist policymakers in Greece in planning further interventions for each subgroup of women in order to reduce the overall CS rate and unnecessary CSs.

What is already done by different societies in reduction of maternal mortality? Are they successful at all?

Maternal mortality represents a major issue for every health system, especially in developed countries that aim on creating protocols to retain a declining pattern. With the appropriate medical supplies and training, some of these countries have made a remarkable progress in preventing maternal morbidity and mortality. On the contrary, developing countries have still made little or even no progress. Identifying determinants and designing strategies is of great importance in order to overcome such difficulties. The aim of this study is to identify the main causes of maternal mortality in the different societies.

Evaluation of the efficacy of cervical pessary combined with vaginal progesterone in women with a short cervix and additional risk factors for preterm delivery.

OBJECTIVE: The aim of this study was to examine the efficacy of a combined management with cervical pessary and vaginal progesterone of women with a singleton pregnancy and a short cervix in both low and high risk-cases based on their previous obstetrical history and maternal factors. STUDY DESIGN: This was a prospective cohort study of women with a singleton pregnancy and a sonographically detected mid-trimester cervical length ≤ 25 mm. The high-risk group consisted of women with a history of a previous spontaneous preterm birth (PB), or a second-trimester miscarriage, or a loop electrosurgical excision procedure of the cervix (LEEP) while the low-risk group of women without such a history. All women were managed with cervical pessary and daily vaginal administration of 200 mg of progesterone. The primary outcome measure was spontaneous delivery before 34 weeks (238 days) of gestation. RESULTS: One hundred ninety-six cases with a CL ≤ 25 mm were detected during the study period. Fifty-two women declined to participate in the study. The remaining 144 women were divided into two groups based on the presence (n = 44) or absence (n = 100) of specific risk factors for PB. The rate of PTB < 34 weeks was similar in both low and high-risk pregnancies while a significantly higher rate of sPTB < 37 weeks was found in women with high-risk pregnancies (p = .005). CONCLUSION: The combined treatment of cervical pessary and vaginal progesterone has a similar influence on preterm delivery rate < 34 weeks, in both low and high-risk women, with a mid-trimester short cervix.

Maternal and neonatal outcomes following a prolonged second stage of labor: A meta-analysis of observational studies.

Several articles investigated the impact of prolonged second stage of labor on maternal and neonatal outcomes; however, strict consensus is still lacking. The purpose of the present meta-analysis is to investigate risk factors that contribute to the pathophysiology of prolonged labor as well as effect sizes of maternal and neonatal morbidity. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar database. Observational studies (prospective and retrospective) were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses we avoided language, country and date restrictions. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with Rstudio. Overall, 13 studies were included in the present systematic review that comprised 337.845 parturient. Prolonged second stage was associated with higher odds of postpartum hemorrhage, chorioamnionitis, endometritis, postpartum fever and obstetric anal sphincter injury. Persistent occiput posterior position and shoulder dystocia were also more prevalent compared to women with normal duration of the second stage. The need for admission to the neonatal intensive care unit was higher as well as the risk of developing neonatal sepsis. On the other hand, the odds of perinatal death were comparable among cases with prolonged and normal duration of the second stage. The results of the present meta-analysis clearly indicate that deliveries following a prolonged second stage of labor are at increased risk of maternal and neonatal complications. The presented effect estimates can be used in current clinical practice during patient counseling.

Presence of amniotic fluid sludge and pregnancy outcomes: A systematic review.

INTRODUCTION: Several studies acknowledge that the presence of amniotic fluid sludge (AFS) is an independent predictive factor for preterm birth. In the present systematic review, we summarize research that focuses on the comparison of pregnancy outcomes among women with and without AFS. MATERIAL AND METHODS: Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were systematically searched from inception. Both observational and randomized controlled studies were considered eligible provided that they reported data on pregnancy outcomes among women with and without AFS. Outcomes were not meta-analyzed because of the high heterogeneity in terms of selected population and outcome reporting. RESULTS: Seventeen studies of 2432 women were included in this review. Six studies evaluated women at high risk for preterm birth. Pregnancies complicated by AFS had a lower gestational age at delivery and increased incidence of preterm delivery at <37 weeks. Neonatal death rates and admission to the Neonatal Intensive Care Unit were also increased. Evidence in low-risk women, those with signs of preterm labor, in those carrying twins, and in women with cervical cerclage or Arabin pessary was extremely limited. CONCLUSIONS: Women with AFS seem to deliver at an earlier gestational age, and preterm birth rates are also increased. Limited data seem to point to neonatal morbidity and mortality being increased. However, the presence of a direct association should not be assumed because the evidence is not adjusted for the presence of confounders.

Progestogens for the prevention of preterm birth and risk of developing gestational diabetes mellitus: a meta-analysis.

BACKGROUND: Several articles have implied that progestogen supplementation during pregnancy to reduce the risk of preterm birth may increase the risk for developing gestational diabetes mellitus. OBJECTIVE: The purpose of the present meta-analysis was to accumulate existing evidence concerning this correlation. DATA SOURCES: We searched Medline (1966-2019), Scopus (2004-2019), Clinicaltrials.gov (2008-2019), EMBASE (1980-2019), Cochrane Central Register of Controlled Trials CENTRAL (1999-2019), and Google Scholar (2004-2019) databases. STUDY ELIGIBILITY CRITERIA: Randomized trials and observational studies were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses, we avoided language, country, and date restrictions. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of included studies was evaluated with the Cochrane risk of bias and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with the Open Meta-Analyst software. Trial sequential analysis was conducted with the trial sequential analysis program. RESULTS: Overall, 11 studies were included in the present meta-analysis that recruited 8085 women. The meta-analysis revealed that women who received 17-alpha hydroxyprogesterone caproate had increased the risk of developing gestational diabetes mellitus (risk ratio, 1.73, 95% confidence interval, 1.32-2.28), whereas women who received vaginal progesterone had a decreased risk, although the effect did not reach statistical significance because of the unstable estimate of confidence intervals (risk ratio, 0.82, 95% confidence interval, 0.50-1.12). Meta-regression analysis indicated that neither the methodological rationale for investigating the prevalence of gestational diabetes mellitus (incidence investigated as primary or secondary outcome) (coefficient of covariance, -0.36, 95% confidence interval, -0.85 to 0.13, P = .154) nor the type of investigated study (randomized controlled trial/observational) (coefficient of covariance -0.361, 95% confidence interval, -1.049 to 0.327, P = .304) significantly altered the results of the primary analysis. Trial sequential analysis suggested that the meta-analysis concerning the correlation of 17-alpha hydroxyprogesterone caproate was of adequate power to reach firm conclusions, whereas this was not confirmed in the case of vaginal progesterone. CONCLUSION: The results of the present meta-analysis clearly indicate that women who receive supplemental 17-alpha hydroxyprogesterone caproate for the prevention of preterm birth have an increased risk of developing gestational diabetes mellitus. On the other hand, evidence concerning women treated with vaginal progesterone remains inconclusive.

Prevention of spontaneous preterm birth.

BACKGROUND: It is estimated that globally, approximately 13 million preterm infants are born annually and a much higher number of pregnancies are characterized by threatening preterm birth. FINDINGS: A proportional inverse correlation between gestational age at delivery and neonatal mortality has been observed which is more prevalent in countries without high standard neonatal care. The socioeconomic burden of preterm birth is enormous, as preterm neonates are particularly prone to severe morbidity that may expand up to adulthood. Several strategies have been proposed for the prevention of preterm birth which can be sub-stratified as primary (when these apply to the general population), secondary (when they target women at risk), and tertiary (optimizing neonatal outcomes when preterm birth cannot any longer be prevented). The aim of this review is to summarize the most important strategies.

Safety and efficacy of the cervical pessary combined with vaginal progesterone for the prevention of spontaneous preterm birth.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of the combined treatment of cervical pessary and endovaginal progesterone for the prevention of spontaneous preterm birth (SPB) in women with a short cervical length (CL) between 20 and 24 weeks of gestation. MATERIALS AND METHODS: This is a prospective study of women with a singleton pregnancy and a sonographically detected mid-trimester CL ≤25 mm. The primary outcome measure was spontaneous delivery before 34 weeks (238 days) of gestation. RESULTS: The study sample consisted of 90 women with a mean CL of 14.2 mm (SD=6.5 mm). Of the women, 34.4% had at least one risk factor for SPB; 7.8% delivered preterm before 34 weeks of gestation, and 25.6%, before 37 weeks. Neonatal death occurred in two (2.2%) cases due to respiratory distress syndrome. Lower body mass index values, history of preterm delivery and number of second trimester miscarriages were independently associated with delivery before 34 weeks. CONCLUSION: The combination of vaginal progesterone and cervical pessary for the prevention of SPB in women with a short cervix is safe and well tolerated. This therapy was associated with pregnancy prolongation, reduced prematurity rate and a low rate of perinatal complications.

Assessment of Uterocervical Angle Width as a Predictive Factor of Preterm Birth: A Systematic Review of the Literature.

BACKGROUND: Uterocervical angle (UCA) has been recently proposed as a potential marker that could accurately predict preterm birth (PTB). The purpose of the present systematic review is to accumulate current evidence and provide directions for future research. MATERIALS AND METHODS: We used the Medline (1966-2018), Scopus (2004-2018), Clinicaltrials.gov (2008-2018), EMBASE (1980-2018), Cochrane Central Register of Controlled Trials CENTRAL (1999-2018), and Google Scholar (2004-2018) databases in our search. RESULTS: Eleven studies were finally included in the present systematic review that evaluated data from 3,018 women. The significant heterogeneity in terms of outcome reporting and outcome reporting measures (use of optimal cut-off values) precluded meta-analysis. However, existing data support that second trimester UCA measurement might be used as a predictive factor of PTB <34 weeks, as at least two studies in unselected singleton pregnancies and two studies in pregnancies with an ultrasonographically shortened cervix seem to support this hypothesis. The most commonly reported cut-off values were 105° and 95°. CONCLUSIONS: UCA measurement during the second trimester of pregnancy may be a useful method of determining women at risk of delivering preterm. However, more studies are needed to assess the reproducibility of these findings and reach conclusive evidence.

Subserosal uterine injection of blue dye for the identification of the sentinel node in patients with endometrial cancer: a feasibility study.

OBJECTIVE: To define the detection rate, sensitivity, and negative predictive value (NPV) of the sentinel node technique in patients with endometrial cancer. METHODS: Patients with endometrial cancer after informed consent underwent subserosal injection of blue dye during hysterectomy in a tertiary gynae/oncology department between 2010 and 2014. The procedure was performed in all cases by the same team including two gynae/oncologist consultants and one trainee. All relevant perioperative clinicopathological characteristics of the population were recorded prospectively. The identified sentinel nodes were removed separately and a completion bilateral pelvic lymphadenectomy followed in all cases. Simple statistics were used to calculate the sensitivity and NPV of the method on per patient basis. RESULTS: Fifty-four patients were included in this study. At least one sentinel node was mapped in 46 patients yielding a detection rate of 85.2%. Bilateral detection of sentinel nodes was accomplished in only 31 patients (57.4%). The mean number of sentinel nodes was 2.6 per patient and the commonest site of identification was the external iliac artery and vein area (66%). Six patients (11%) had a positive lymph node, and in five of them, this was the sentinel one yielding a sensitivity of 83.3% and an NPV of 97.5%. The overall detection rate improved significantly after the first 15 cases; however, this was not the case for the bilateral detection rate. CONCLUSION: Our study is in accordance with previous studies of sentinel node in endometrial cancer and further demonstrates and enhances the confidence in the technique. In the current era of an ongoing debate on whether a systematic lymphadenectomy in patients with endometrial cancer is still necessary, we believe that the sentinel node is an acceptable alternative and should be applied routinely in tertiary centres following a strict algorithm.

Laparoscopic Cystectomy In-a-Bag of an Intact Cyst: Is It Feasible and Spillage-Free After All?

This prospective study was conducted to assess the feasibility of laparoscopic cystectomy of an intact adnexal cyst performed inside a water proof endoscopic bag, aiming to avoid intraperitoneal spillage in case of cyst rupture. 102 patients were recruited. Two of them were pregnant. In 8 of the patients the lesions were bilateral, adding up to a total of 110 cysts involved in our study. The endoscopic sac did not rupture in any case. Mean diameter of the cysts was 5.7 cm (range: 2.3-10.5 cm). In 75/110 (68.2%) cases, cystectomy was completed without rupture, whereas in the remaining 35/110 (31.8%) cases the cyst ruptured. Minimal small spillage occurred despite every effort only in 8/110 (7.2%) cases with large (>8 cm) cystic teratomas. There were no intraoperative or postoperative complications. We concluded that laparoscopic cystectomy in-a-bag of an intact cyst is feasible and oncologically safe for cystic tumors with a diameter < 8 cm. Manipulation of larger tumors with the adnexa into the sac may be more difficult, and in such cases previous puncture and evacuation of the cyst contents should be considered.

Fetal loss following second trimester amniocentesis. Who is at greater risk? How to counsel pregnant women?

OBJECTIVE: The purpose of this retrospective observational cohort study was to determine the impact of certain risk factors on fetal loss, after mid-trimester amniocentesis. MATERIAL AND METHODS: Six thousand seven-hundred and fifty-two (6752) consecutive amniocenteses with known pregnancy outcome performed during a 7-year period (2004-2010) were included in this study. Different maternal-, fetal- and procedure-related factors were evaluated in this study. RESULTS: During this 7-year period, 6752 cases who underwent amniocentesis, with complete data available were evaluated for the outcome and risk factors mentioned. Total fetal loss rate (FLR) up to the 24th week was 1.19%. Risk factors associated with increased risk of fetal loss after amniocentesis were maternal age (OR:2.0), vaginal spotting (OR:2.2) and serious bleeding (OR:3.5) during pregnancy, history of 2nd trimester termination of pregnancy (OR:4.0), history of more than three spontaneous (OR:3.0) or surgical first trimester abortions (OR:2.1), fibromas (OR:3.0) and stained amniotic fluid (OR:6.1). CONCLUSIONS: Amniocentesis is a safe-invasive procedure for prenatal diagnosis with total FLR of 1.19% in our institution during the study period. The present study has emphasized the significance of certain risk factors for adverse outcome and therefore the need to individualize the risk.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

BACKGROUND/AIM: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). PATIENTS AND METHODS: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. RESULTS: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). CONCLUSION: AR expression does not seem to play a prognostic role in TNBC.

Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas.

BACKGROUND: Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas. METHODS: Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography. RESULTS: Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues. CONCLUSIONS: This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.

Risk for fetal loss and prematurity after 12,413 second trimester amniocenteses in a single center.

OBJECTIVES: The purpose of this retrospective controlled study is to estimate the risk for fetal loss and preterm delivery attributed to second trimester amniocentesis from a single tertiary center. METHODS: The study group consists of 12,413 singleton pregnancies with consecutive amniocenteses, performed in a single tertiary center during a 15-year period (1996-2010) with known pregnancy outcome. The control group consisted of 6993 pregnancies with negative second trimester screening for aneuploidies during the same period who did not have any invasive test. The two groups were compared in terms of fetal loss rate up to 24 weeks and premature deliveries. RESULTS: Total fetal loss up to 24 weeks in the study group, excluding terminations of pregnancy, was estimated at 1.25% (1.05%-1.45%, confidence interval [CI]: 95%). In the control group the loss rate was 0.65% giving a procedure related fetal loss rate of 0.6% which was not found to be a statistically significant difference. Delivery before the 28th, 32nd, 34th, and 37th week in the study group was reported in 0.2%, 0.8%, 1.2% and 8.1% respectively, and it was not statistically different from controls. CONCLUSION: The present study has shown that the risk of miscarriage that can be attributed to amniocentesis in our institution is 0.6%, and this is not statistically significant when compared with cases without any invasive procedure during pregnancy. Similarly, the risk for preterm labor was not statistically significant when compared with controls.