The Contribution of Multiple Pregnancies in Stillbirths in Greece: A Time-Trend Analysis.

Introduction Multiple pregnancy is an established risk factor for fetal death. This study aimed to examine the impact of multifetal pregnancies on stillbirth rates (SBRs) in the Greek population. Methods Data on live births and stillbirths by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. The SBR for multiple and single gestations, and the population attributable risk (%) (PAR (%)) stillbirth attributable to multifetal gestations were calculated, and temporal trends were assessed using joinpoint regression analysis, with annual percentage changes (APC) and 95% confidence interval (95% CI). Results In the period 1957-2021, multiple pregnancies accounted for 9.4% of total stillbirths in Greece and the overall relative risk of fetal death among multifetal gestations was 3.34, in comparison with singletons. The SBR in multiple births remained unchanged from 1957 to 1976 and showed downward trends from 1976 to 2021 (APC = -3.0, 95% CI: -3.4 to -2.7, p < 0.001). PAR (%), after two decades of stability, showed an increasing trend over the period 1975-2011 (APC = 3.4, 95% CI: 2.8 to 4.0, p < 0.001), which was reversed in the more recent decade 2011-2021 (APC = -6.1, 95% CI: -9.6 to -2.5, p = 0.001), with PAR (%) decreasing from a historical high of 19.3% in 2012 to 8.6% in 2021. Conclusion The high incidence of multiple births has a considerable impact on stillbirth rates in the Greek population. The recent downward trends of SBR and PAR (%) of multiple gestations are encouraging, however more measures and targeted interventions are needed to improve perinatal outcomes in multifetal gestation.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021-2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415-6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887-13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400-9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51-15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02-16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05-15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Second Trimester Amniotic Fluid Angiotensinogen Levels Linked to Increased Fetal Birth Weight and Shorter Gestational Age in Term Pregnancies.

BACKGROUND: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin-angiotensin system with fetal growth abnormalities. METHODS: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. RESULTS: Mean angiotensinogen values were 3885 ng/mL (range: 1625-5375 ng/mL), 4885 ng/mL (range: 1580-8460 ng/mL), and 4670 ng/mL (range: 1995-7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. DISCUSSION: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.

Robotic-assisted fertility sparing surgery in gynecological oncology.

While gynecological malignancies are more commonly diagnosed in elderly women, a substantial proportion of women will still be diagnosed with some type of gynecologic cancer during their reproductive age. Over 10% of newly diagnosed ovarian cancers and over one third of newly diagnosed cervical cancers involve women who are under the age of 45. This, coupled with the rising trend of women having their first child after the age of 35, has led to a concerning prevalence of complex fertility issues among women who have been diagnosed with cancer. Since the advent of robotic-assisted surgeries in gynecology, there has been a rise in the occurrence of these procedures. Fertility preserving gynecological surgeries require precise management in order to avoid fertility disorders. Therefore, we conducted a narrative review of robotic assisted fertility sparing surgery in gynecologic malignancies in order to highlight the role of this approach in preserving fertility.

Inguinal Lymph Node Metastasis as Sole Manifestation of Ovarian / Fallopian Tube Cancer: a Review of the Literature.

Background: Ovarian/fallopian tube cancer is the deadliest gynecological malignancy. Most cases are diagnosed at an advanced stage, typically after the cancer has spread to the peritoneal cavity, or via lymphatic drainage. The presence of distant lymph node metastasis in the inguinal region is a rare manifestation of lymphatic metastasis. Since the 2014 FIGO staging revision, ovarian cancer patients with inguinal metastasis are classified as stage IVB. However, the clinical significance of such an upstaging remains under investigation. Materials and Methods: Both Scopus and PubMed / MEDLINE databases were utilized, by inputting the following combination of keywords: (Ovarian cancer OR Fallopian tube cancer) AND (Inguinal lymph node AND Metastasis) on June 31st, 2023. The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. Results: Twelve patients from equal number of case reports were included in our review. Mean age of diagnosis was 56,5 years old, with 3 out of 12 women to be premenopausal at the time of diagnosis. Regarding the histologic type, 67% (8 out of 12) of the cases were serous adenocarcinoma and 4 patients (33%) were diagnosed with fallopian tube malignancy. All patients, except one, were treated with primary cytoreductive surgery. In all patients optimal cytoreductive surgery was achieved. All patients, except one, received adjuvant chemotherapy. Regarding the disease-free survival, mean DFS is calculated approximately at 2 years (23,1 months). Conclusion: Inguinal lymph node metastases from ovarian / fallopian tube malignancy as initial site of metastasis is extremely rare. However, patients with inguinal masses should be investigated for ovarian / fallopian malignancy. Further investigation ought to be conducted to enlighten the pathway and the oncological significance of inguinal lymph node metastasis in ovarian cancer patients.

Uterine collision tumor (PEComa and endometrioid carcinoma) in a tuberous sclerosis patient: a case report.

Perivascular epithelioid cell tumors are very rare mesenchymal neoplasms arising in various locations, such as the female genital tract, kidney, lung, prostate, bladder, pancreas, soft tissues, and bone. They possess a unique immunophenotype, co-expressing myogenic and melanocytic markers; molecular findings include mutations of tuberous sclerosis complex and translocations of transcription factor E3, a member of the microphthalmia transcription factor gene family. We herewith report a uterine collision tumor consisting of a perivascular epithelioid cell tumor and a moderately differentiated endometrial endometrioid carcinoma in a patient with genetically proven tuberous sclerosis; two leiomyomas were also found in contact with the tumor. Although two such cases one with a benign and another with a malignant perivascular epithelioid cell tumor have previously been reported, ours is, to our knowledge, the first reported in a tuberous sclerosis patient.

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns.

BACKGROUND: Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. METHODS: This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. RESULTS: NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. CONCLUSIONS: Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Prenatal Exposure to Bisphenol A: Is There an Association between Bisphenol A in Second Trimester Amniotic Fluid and Fetal Growth?

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual's diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = -0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

Is There a Correlation between Apelin and Insulin Concentrations in Early Second Trimester Amniotic Fluid with Fetal Growth Disorders?

INTRODUCTION: Fetal growth disturbances place fetuses at increased risk for perinatal morbidity and mortality. As yet, little is known about the basic pathogenetic mechanisms underlying deranged fetal growth. Apelin is an adipokine with several biological activities. Over the past decade, it has been investigated for its possible role in fetal growth restriction. Most studies have examined apelin concentrations in maternal serum and amniotic fluid in the third trimester or during neonatal life. In this study, apelin concentrations were examined for the first time in early second-trimester fetuses. Another major regulator of tissue growth and metabolism is insulin. MATERIALS AND METHODS: This was a prospective observational cohort study. We measured apelin and insulin concentrations in the amniotic fluid of 80 pregnant women who underwent amniocentesis in the early second trimester. Amniotic fluid samples were stored in appropriate conditions until delivery. The study groups were then defined, i.e., gestations with different fetal growth patterns (SGA, AGA, and LGA). Measurements were made using ELISA kits. RESULTS: Apelin and insulin levels were measured in all 80 samples. The analysis revealed statistically significant differences in apelin concentrations among groups (p = 0.007). Apelin concentrations in large for gestational age (LGA) fetuses were significantly lower compared to those in AGA and SGA fetuses. Insulin concentrations did not differ significantly among groups. CONCLUSIONS: A clear trend towards decreasing apelin concentrations as birthweight progressively increased was identified. Amniotic fluid apelin concentrations in the early second trimester may be useful as a predictive factor for determining the risk of a fetus being born LGA. Future studies are expected/needed to corroborate the present findings and should ideally focus on the potential interplay of apelin with other known intrauterine metabolic factors.

Experience With J-Plasma Device in Achieving Complete Cytoreduction in Patients With Ovarian Cancer.

BACKGROUND/AIM: Ovarian cancer remains one of the most lethal malignancies in women. Optimal surgical cytoreduction is the most important prognostic factor of survival in patients with advanced ovarian cancer. The helium gas plasma device (J-Plasma) has recently been introduced into surgical treatment of these patients with some promising results. The aim of this study was to evaluate the utility of J-Plasma in the debulking surgery of patients with ovarian cancer. PATIENTS AND METHODS: A single center retrospective analysis of the characteristics of patients with ovarian cancer who had cytoreductive surgery with the use of J-Plasma device from January of 2020 until July of 2022 was conducted. RESULTS: A total of 13 patients were included in our study. Six patients were treated with primary debulking surgery, whereas seven underwent interval debulking surgery after neoadjuvant chemotherapy. Complete cytoreduction was achieved in nine patients (64%), and CC-1 in four patients. Most of the patients did not face any major complications; only 1 patient suffered from small bowel fistula that needed relaparotomy. CONCLUSION: J-Plasma can safely be used in ovarian cancer debulking surgeries performed by gynecologic oncologists in tertiary centres. This technology can safely increase the complete cytoreduction rates.

Follow the River to the Lake: Sentinel Lymph Node Identification Using the Robotic Platform in Endometrial Cancer Patients.

Sentinel lymph node biopsy for the management of endometrial cancer patients has been introduced into surgical staging of these patients. Several articles and guidelines have evaluated and found sentinel lymph node biopsy as an efficient and oncological safe procedure. The aim of this article is to highlight the most important tips and tricks in order to optimize sentinel lymph node identification and dissection based on our experience. Each step of sentinel lymph node identification technique is analyzed. Tips and tricks, such as site and time of indocyanine green dye injection are essential in optimal identification of sentinel lymph node in patients with endometrial cancer. The standardization of the technique and the recognition of anatomic landmarks are essential as they lead to an improved and effective identification of sentinel lymph node.

Temporal Trends in Multiple Births in Greece: The Evolution of an Epidemic.

Introduction Multiple births constitute the dominant adverse effect of fertility treatments and are associated with increased perinatal risks. The aim of this study was to comprehensively examine and present time trends in multiple births in Greece. Methods Data on live births by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. Temporal trends in multiple birth rates (MBR), twin birth rates (TwBR), as well as in triplet and higher-order birth rates (Tr+BR) were assessed using joinpoint regression analysis, and the annual percentage changes (APC) were calculated with a 95% confidence interval (95% CI) and level of statistical significance (p < 0.05). Results The MBR in Greece showed a downward trend from 1957 to 1979 (APC = -1.7, 95% CI: -2.0 to -1.4, p < 0.001). However, the rate started to climb in the 1980s, accelerated during the 1990s, and continued to rise in the two most recent decades, reaching a historic high and a world record of 57.2 per 1,000 births in 2021, i.e., a 3.4-fold increase since 1985. The TwBR increased from an all-time low of 16.5 per 1,000 births in 1978 with APC = 1.4 (95% CI: 0.2 to 2.5, p = 0.021) during 1979-1989, APC = 6.3 (95% CI: 5.5 to 7.2, p < 0.001) during 1989-2001, and APC = 1.2 (95% CI: 0.8 to 1.5, p < 0.001) during the last two decades (2001-2021). The Tr+BR, after an all-time low of 17.5 per 100,000 births in 1966, increased dramatically from 1982 to 2000 (APC = 12.4, 95% CI: 9.6 to 15.2, p < 0.001), leveled off during 2000-2011, and after reaching a historic maximum of 351.1 per 100,000 births in 2010, there was a sharp decreasing trend during the last decade (2011-2021: APC = -12.1, 95% CI: -16.8 to -7.2, p < 0.001). Conclusion The dramatic increases in maternal age as well as in medically assisted conceptions have resulted in an epidemic increase in MBR in Greece reaching world record levels. During the last decade, there was an encouraging decline in the Tr+BR; however, the TwBR has continued to trend upwards.