COX isozymes and non-uniform neoangiogenesis: What is their role in endometriosis?

This literature review compared the efficacy in of NSAIDs with a placebo in pain relief and disease regression of endometriosis. Despite the poor evidence found, the results showed that NSAIDs were more effective in pain relief with regressive effects on the endometriotic lesions compared to placebo. We postulate herein that COX-2 is chiefly responsible for pain whilst COX-1 is responsible mainly for the establishment of endometriotic lesions. Hence, there must be a temporal difference in the activation of the two isozymes. We differentiated between two pathways in the conversion of arachidonic acid to prostaglandins by the COX isozymes referred to as 'direct' and indirect', supporting our initial theory. Finally, we postulate that there are two stages of neoangiogenesis in the formation of endometriotic lesions; 'founding' that first establishes blood supply and 'maintenance' that upkeeps it. This is fertile ground for further research in a niche that needs more literature. Its aspects may be diversely explored. The theories we propose offer information for a more targeted treatment of endometriosis.

Screening for monogenic subtypes of gestational diabetes in a high prevalence island population - A whole exome sequencing study.

AIMS: The reported frequency of monogenic defects of beta cell function in gestational diabetes (GDM) varies extensively. This study aimed to evaluate the frequency and molecular spectrum of variants in genes associated with monogenic/atypical diabetes in non-obese females of Maltese ethnicity with GDM. METHODS: 50 non-obese females who met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosis of GDM and with a first-degree relative with non-autoimmune diabetes were included in this study. Whole exome capture and high throughput sequencing was carried out. Rare sequence variants were filtered, annotated, and prioritised according to the American College for Medical Genetics guidelines. For selected missense variants we explored effects on protein stability and structure through in-silico tools. RESULTS: We identified three pathogenic variants in GCK, ABCC8 and HNF1A and several variants of uncertain significance in the cohort. Genotype-phenotype correlations and post-pregnancy follow-up data are described. CONCLUSIONS: This study provides the first insight into an underlying monogenic aetiology in non-obese females with GDM from an island population having a high prevalence of diabetes. It suggests that monogenic variants constitute an underestimated cause of diabetes detected in pregnancy, and that careful evaluation of GDM probands to identify monogenic disease subtypes is indicated.

Biological and biochemical characteristics of a Mediterranean population with Gestational Diabetes Mellitus.

The interplay of various nutrients provided to the developing foetus determines the growth potential of the conceptus. This study assessed the inter-relationship between these nutrients in a Mediterranean population including 1062 pregnant, previously non-diabetic women. These underwent an oral glucose tolerance test (oGTT) and were accordingly classified into gestational hyperglycaemic and normoglycaemic groups. Fasting insulin, HbA1c, and lipid profiles were further assessed, and the anthropomorphic characteristics of the mother and child at birth were measured. Lipid profiles were compared between the two groups and related to the biological characteristics of the mother and child at birth. Gestational hyperglycaemia was significantly associated with elevated triglycerides (P<0.0001) and decreased low density lipoprotein cholesterol (LDL-C) (P=0.02). There were no significant changes in total cholesterol and high density lipoprotein cholesterol (HDL-C) levels. Maternal BMI correlated positively with the various glycaemic indices (P<0.0001) and triglycerides (P<0.0001), but inversely with cholesterol (P<0.0001), HDL-C (P<0.0001) and LDL-C (P<0.0001). The infant birth weight correlated positively with maternal body weight (P<0.0001), LDL-C (P<0.0001) and the glycaemic indices (P<0.0001), but negatively with cholesterol (P<0.0001), triglycerides (P<0.0001), HDL-C (P<0.0001) and FBG (P<0.0001). This study confirms that the maternal body mass index (BMI), insulin resistance, and LDL-C levels positively contribute towards foetal growth, whereas a negative correlation was noted with cholesterol, triglycerides, and HDL-C.

Pregnancy outcomes in substance-misusing pregnant women: A 10-year retrospective study.

In this ten-year retrospective study we were able to show that Maltese substance-misusing mothers (SMMs) have significantly different socio-biological characteristics from mothers in the general population which seem to impact on neonatal outcomes. Significant differences from the general population were noted in the SMM's age, age at first pregnancy, marital status, educational background, number of cigarettes smoked, number of offspring and weight gained in pregnancy. SMMs booked their pregnancy in hospital later than the general population. On the other hand their infants had a lower mean birth weight and head circumference, had lower Apgar scores, were of lesser gestational age and premature. They were less breast-fed and stayed longer in hospital after their birth.

A proposal for the use of uniform diagnostic criteria for gestational diabetes in Europe: an opinion paper by the European Board & College of Obstetrics and Gynaecology (EBCOG).

Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent across Europe, and the development of a uniform GDM screening strategy is necessary. Such a strategy would create opportunities for more women to receive timely treatment for GDM. Developing a consensus on screening for GDM in Europe is challenging, as populations are diverse and healthcare delivery systems also differ. The European Board & College of Obstetrics and Gynaecology (EBCOG) has responded to this challenge by appointing a steering committee, including members of the EBCOG and the Diabetic Pregnancy Study Group (DPSG) associated with the EASD, to develop a proposal for the use of uniform diagnostic criteria for GDM in Europe. A proposal has been developed and has now been approved by the Council of the EBCOG. The current proposal is to screen for overt diabetes at the first prenatal contact using cut-off values for diabetes outside pregnancy, with particular efforts made to screen high-risk groups. When screening for GDM is performed at 24 weeks' gestation or later, the proposal is now to use the 75 g OGTT with the new WHO diagnostic criteria for GDM. However, more research is necessary to evaluate the best GDM screening strategy for different populations in Europe. Therefore, no clear recommendation has been made on whether a universal one-step, two-step or a risk-factor-based screening approach should be used. The use of the same WHO diagnostic GDM criteria across Europe will be an important step towards uniformity.

The medical aspects of the 1565 Great Siege of Malta.

The 1565 Siege of Malta served as a turning point in the westward Ottoman advance. The 4-month long siege was resisted by the indomitable belief of the defenders that their cause was just and holy. It also required prior detailed organisation to ensure sufficient war materials and that the overall health of the combatants and non-combatants was maintained throughout the months of the siege. This article reviews the contemporary and historical sources relating to the conflict to identify the medical operational plans used by the military during this historic siege.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth: A position statement by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Pre-term birth is associated with significant neonatal morbidity and mortality. Pre-term births are associated with significant health and neuro-developmental risks in childhood and adulthood. Women with multiple pregnancies are at much higher risks. Low levels of omega-3 long-chain polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are associated with higher risk of pre-term labour and increased consumption of foods rich in omega-3 PUFA or supplements are associated with a 11 % and 42 % risk reduction of early and late preterm births, respectively.

European Board and College of Obstetrics and Gynaecology position statement on maternal mortality surveillance in Europe.

Maternal mortality data and review are important indicators of the effectiveness of maternity healthcare systems and an impetus for action. Recently, a rising incidence of maternal mortality in high income countries has been reported. Various publications have raised concern about data collection methods at country level, as this usually relies mainly on national vital statistics. It is therefore essential that the collected data are complete and accurate and conform to international definitions and disease classification. Accurate data and review can only be truly available when an Enhanced Obstetric Surveillance System is in place. EBCOG calls for action by national societies to work closely with their respective ministries of health to ensure that high quality surveillance systems are in place.

Variations in sexual and reproductive health services for the provision of comprehensive contraceptive and abortion services across Europe: A questionnaire-based study commissioned by the European Board and College of Obstetrics & Gynaecology (EBCOG) and European Society of Contraception (ESC).

A questionnaire-based study was jointly organised by European Board and College of Obstetrics and Gynaecology and European Society of Contraception to evaluate the current status as regards access and quality of care regarding contraception, abortion care, and pre-conceptional counselling and care among the 26 European countries. There are considerable variations among these countries as regards the provision of contraceptive services and abortion care. There is ample room for improvement through European training and education programs. However, the most important difference is the absence of a comprehensive network of healthcare providers in various countries to deliver these services at different points of access. There is notable absence of educational programs and instructional materials tailored specifically for nurses and midwives in several countries. This deficiency impedes the professional development and skills enhancement of these healthcare professionals, potentially compromising the quality of healthcare services provided to women in these countries.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

The potential impact of tobacco use on female fertility and pregnancy outcomes: An invited scientific review by EBCOG.

Tobacco use in pregnant women remains prevalent with an estimated prevalence of 8.1 % in the European region. In whatever form it is partaken, tobacco use is associated with significant short- and long-term consequences for both the mother and the progeny thus making the habit an important obstetric and public health concern. It is recommended that an active intervention policy should be adopted by healthcare providers to promote preconception smoking cessation and provide services for counselling with behavioural modification support, and the provision of smoking cessation pharmaceutical services. Women who continue to smoke should have closer antenatal surveillance throughout the whole of pregnancy.

High-intensity exercise during pregnancy - A position paper by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Most guidelines recommend regular physical exercise to all pregnant women. However, because of the anatomical and physiological changes which occur during pregnancy, high-intensity exercise and forms of extreme sports can place the pregnant woman and her fetus at risk of harm.

Harmful effects of opioid use in pregnancy: A scientific review commissioned by the European Board and College of obstetrics and gynaecology (EBCOG).

Caring for pregnant women who have a recreational opioid use disorder is a common clinical challenge in modern obstetric care. These are an elusive population who often have multiple social issues that complicate their pregnancy management. Comprehensive and supportive maternal care can motivate these mothers to change her lifestyle. Multidisciplinary non-judgemental approach with appropriate medication and management, can result in good pregnancy outcomes for mother and her baby.

Commercial Air And High-Altitude Travel by Pregnant Women: A scientific review commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Air travel and long distance travel may have adverse effect on the pregnancy-induced physiology and these effects are more marked among those with pre-existing medical conditions. There are significantly increased risks of deep venous thrombosis, inflight transmission of infections, preterm labour, and other significant obstetric and medical complications that may be exacerbated by the flight and may require emergency care. Transient changes in cardiotocographic tracings during third trimester of pregnancy have been reported following air travel. It has been suggested that pregnant members of the flight crew may be at a slightly higher risk of spontaneous miscarriages. There are no contra-indications for healthy pregnant women on air travel. Those with underlying medical conditions should only embark on long distance travel following consultation with their obstetrician. Pregnant women should be advised to familiarise themselves with the healthcare system in the country/region they will be visiting and draw up an emergency plan of how they will contact the healthcare system at their destination.

The role of traditional complementary physical interventions in obstetrics - A scientific review commissioned by the European board and college of obstetrics and gynaecology (EBCOG).

Because of the fear of the use of pharmacological agents, many pregnant women are opting to use alternative management modalities either as primary management or to compliment standard contemporary medical practices. The traditional complementary physical interventions of acupuncture, acupressure, and electrostimulation have a long tradition of use in traditional Chinese medical practice and are advocated for the management of antenatal conditions such as spontaneous miscarriages, gastrointestinal, respiratory, and urinary problems. They have also been advocated as useful to help the process of labour in promoting a cephalic delivery, induction/augmentation of labour and pain relief. Postpartum these modalities have been said to help the secretion and production of milk. While a number of studies, some randomized controlled, have suggested a potential role for these traditional complementary physical interventions, systematic reviews have generally failed to show a definite conclusive beneficial role and all reviews generally suggest the need for further controlled research in the field. Since no adverse effects appear to be associated with the use of these modalities in pregnancy, such modalities of management can be considered but only as an adjuvant to standard pharmacological management after a full clinical assessment has ruled out underlying pathology.

The consequences of armed conflict on the health of women and newborn and sexual reproductive health - A position statement by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Armed conflict brings about significant health-related consequences to the non-combatant population especially the elderly, women, and children. The consequences for women extend further than battle-related deaths. One important consequence of conflict is the population displacement resulting from individuals and families seeking safety in non-conflict zones. This forced migration places women at risk of gender-based violence during their journey and for this reason the host countries should ensure that the migrants are given access to reproductive health services, including providing emergency contraception and abortion. In the conflict zone, the collapse of all social support, including healthcare services, contribute towards a marked deterioration in the level of care provided to ensure reproductive health and safe motherhood. In addition, the community living the conflict zone is at an increased risk of community infectious disease and poor management of chronic illness. Women and children are almost always innocent victims of war. The international community must act effectively to primarily avoid conflict by sound diplomatic intervention and, when diplomacy fails, reduce the consequences of conflict.

Provision of antenatal care in Europe-A scientific study commissioned by European Board and College of Obstetrics and Gynaecology (EBCOG).

Differences in the way health care delivery across countries may have important impacts on health outcomes and can result in inequalities. A questionnaire survey of members of national societies through EBCOG and EAPM was carried out in 2021. A total of 53 responses were received from 26 countries. Most countries reported that routine antenatal care is primarily delivered by medical staff, involving obstetric specialists or family doctors mostly in government-run facilities. Women from minority groups are able to access antenatal care easily in most countries. Less than 10% of women did not attend antenatal care throughout the pregnancy. Most booking for antenatal care takes place in the first trimester and the number of visits range from 6 to 10 depending on parity. Most countries provide routine ultrasound with 2-3 reported scans performed by specifically trained health care professionals. Facilities for prenatal screening/diagnosis of malformations in both low- and high-risk cases varied across Europe. While antenatal care is relatively standardized throughout Europe, important differences still exist in care delivery and accessibility to care. Antenatal preventive strategies appear to be variably available throughout Europe.

GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic Tumors­Current Challenges and Future Directions

More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on expert opinion, retrospective studies, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges through the creation of a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, "Basic and Translational Research on Rare Gynecological Cancer") have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state-of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide.

EBCOG position statement about the use of herbal medication during pregnancy.

Pregnant women often resort to herbal medication to ameliorate the disturbing symptoms associated with pregnancy in the mistaken belief that these are safe and carry no potential harmful effects to the developing fetus. Healthcare personnel must be cognizant of the potential adverse side effects of these substances to be able to better advise their patients.