Αποτελέσματα της εργασίας παρουσιάστηκαν στο 4th ISNS Middle East-North Africa Regional Meeting, Limassol, Cyprus, March 8-11, 2020, “Introducing and expanding Newborn Screening in the MENA region”.

Gkika Anna¹, Papathanasiou Mando¹, Platis Dimitrios¹, Voutetakis Antonis², Mastorakos George³, Kanaka-Gantenbein Christina², Girginoudis Panagiotis¹, Joanne Traeger-Synodinos⁴ and Iliadi Alexandra¹

¹Institute of Child Health, Hellenic Newborn Screening Laboratory, Athens, Greece
³Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital
³Unit of Endocrinology, Diabetes Mellitus and Metabolism, ARETAIEION Hospital, Faculty of Medicine, National and Kapodistrian University of Athens
⁴Laboratory of Medical Genetics, National and Kapodistrian University of Athens

Introduction: Congenital hypothyroidism (CH) is the most frequently encountered Congenital Endocrinopathy, with a prevalence of 1:1500-3000 births, and may lead to mental subnormality if not diagnosed and treated promptly. Implementation of Neonatal Screening Programs for Congenital Hypothyroidism (CH) have reduced related nosologies and eradicated CH-associated mental impairment. The Hellenic Newborn Screening Program is carried out by the Institute of Child Health (ICH) which is also responsible for final diagnosis, treatment initiation and clinical and hormonal follow-up of CH patients. 

Objectives: The identification of biomarker-polymorphisms (SNPs) in genes associated with Thyroid hormones metabolic pathways that can be correlated with clinical features of CH, such as L-T4 replacement therapy response, would be an extremely valuable tool for the prognosis of the disease at a very early stage. Genetic analysis was focused on the detection of 6 single nucleotide polymorphisms (SNPs), rs1991517, rs225014, rs939348, rs4704397, rs12095080, rs11206244 in TSHR, DIO1, DIO2, THRa, PDE8B genes. The present study is the first attempt to correlate specific polymorphisms with clinical features in CH children with a known pathoetiology of the disease.

Methods: Laboratory, clinical and ultrasonographic data were recorded from the medical records of children diagnosed with CH by the Hellenic Neonatal CH Screening Program. Patients with specific inclusion criteria (n= 400): CH dyshormonogenesis/transient CH, age >3 years old, natural conception, monocytic pregnancy, non- syndromic, non- low birth-weight were selected.  DNA was isolated and genotyped with RE-PCR. Statistical analysis was performed to compare clinical features such as birth weight, gestational age, TSH and FT4 before LT-4 substitution, Guthrie TSH level, dose at 1 and 3 years and BMI at 3 and 5 years with different genotypes.

Results/Discussion: CH is a multifactorial and polygenetic disease with a variety of features and phenotypes. Identifying genetic biomarkers that might help us predict LT-4 substitution dose, clinical outcome/severity of disease is of paramount importance.

Vasiliki M. Korvesi MD, MSc | Ioanna Chouvarda Prof. | George Mastorakos Prof. | Dimitrios G. Goulis Prof.

DOI: 10.1111/eci.13291

Abstract
Background: Despite the production of clinical practice guidelines (CPGs) in many medical areas, their use is not sufficiently adopted in clinical practice. Incorporation of CPGs in knowledge tools (KnowT) or decision support systems (DSS) for routine use can improve healthcare providers’ compliance to CPGs. Materials and methods: Clinical practice guidelines for gestational diabetes mellitus (GDM) were searched for, collected and compared. The CPG that met prespecified criteria ([a] published by a European or American organization between 2010 and 2018, [b] being developed a systematic way and [c] having statements of “level of evidence” and “strength of recommendation”) was chosen for implementation (Endocrine Society, 2013). Its recommendations were deconstructed, re-organized and reconstructed as an algorithm (in the form of a flowchart), which was integrated into a KnowT. Content completeness and evaluation of CPG by the Guideline Implementability Appraisal tool (GLIA) were performed as well. The primary objective was the development of a clinical algorithm in the field of GDM and its integration into a KnowT. The secondary objective was to demonstrate the completeness of the CPG content and evaluate its implementability in the KnowT. Results: Endocrine Society 2013 CPG was restructured as a flowchart, and a KnowT was constructed with the use of the “Openlabyrinth” software. The completeness of the content was confirmed, and GLIA appraisal demonstrated its implementability. Conclusion: Endocrine Society 2013 CPG for GDM is a complete set of recommendations. Its structure makes possible the design of a clinical algorithm and its implementation into a KnowT.

Olga Triantafyllidou, Georgios Kolovos, Charalambos Voros, Athanasios Vlachos, Panagiotis Vakas, Nikos Vlahos

PMID: 31979988, DOI: 10.1080/14647273.2019.1704451

Abstract

The risk of recurrence after surgery is a major problem in women who are suffering from endometriosis. The prescription oral contraceptives (OCs) in the treatment of endometriosis-related pain, in women who do not desire fertility, is still controversial. The aim of this prospective cohort study is to evaluate the time until the reduction in the mean intensity of dysmenorrhoea and deep dyspareunia takes effect, for patients who use combined OCs in the accepted cyclic manner, versus in the continuous fashion as after the laparoscopic excision of endometriosis. A total of 28 patients diagnosed with endometriosis who underwent surgical treatment were offered at least a 12 months course of oral contraceptives. The intensity of both symptoms was reduced at the end of observational period in both groups. The use of continuous OCs (11 patients) was associated with a more pronounced reduction in the mean intensity of dyspareunia and dysmenorrhoea at 9 (p = 0.004) and 6 (p = 0.003) months respectively as compared to the cyclic group (17 patients).

Keywords: Oral contraceptives; dysmenorrhoea; dyspareunia; endometriosis; laparoscopy.

Foteini Anifantaki, Ioannis Boutas, Theodoros Kalampokas, Emmanouil Kalampokas, Chrisostomos Sofoudis, Nikolaos Salakos

Abstract
Background Endometriosis is a common, estrogen-dependent, gynecological disease, which is defined as the presence of endometrial tissue outside the uterine cavity. Current data have associated endometriosis with specific malignancies, including ovarian and breast cancer. Purpose The purpose of our study is to summarize and present published literature providing evidence regarding the possible relationship between endometriosis and breast cancer. Methods Pubmed and Scopus databases were searched systematically for studies that sought to identify a potential association of endometriosis and breast cancer. 15 relevant articles were retrieved and included in the present review. Results A small number of observational studies have shown a correlation of endometriosis and breast cancer. Other studies found that the risk of breast cancer increases with age. The scenario of an early interruption of the inflammatory process, derived from endometriosis, by oophorectomy and a possible consequent decrease in the risk of breast cancer has also been proposed. The hypothesis that both conditions could be related through common mutations on BRAC1 and BRAC2 genes has also been investigated. Conclusion The available published evidence is inconclusive. Further studies are needed to evaluate the association of endometriosis and breast cancer and the possible pathogenetic pathways that relate the two disorders.

Keywords: Endometriosis  Breast cancer  Breast neoplasm  Breast malignancies

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Evangelos Iliopoulos*

Background: During the last years new targeted regimen for several autoimmune diseases has been developed leading to an ameliorated quality of life for these patients. Nevertheless, their fertility potential seems to be impaired either by the activity of the autoimmune diseases or by the medical treatment used to suppress these conditions. This systematic review intends to reveal how autoimmune diseases and their regimen affect male fertility.
Methods: A search of English-language articles from electronic databases was conducted. The results that were used referred to impaired fertility in male patients with Systemic Lupus Erythematosus, Behcet’s disease, gout, dermatomyositis, celiac disease, rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis and sarcoidosis.
Conclusion: Thirty-nine articles were finally included regarding the following diseases: Dermatomyositis, Systemic Lupus Erythematosus, Behcet’s disease, Gout, Celiac disease, Rheumatoid arthritis, Ankylosing spondylitis, Inflammatory bowel disease, Psoriasis, Sarcoidosis as well as two systematic reviews. Cyclophosphamide therapy seems to impair fertility in male patients with Systemic Lupus Erythematosus and Behcet’s disease. Colchicine use may lead to sperm abnormalities in patients with gout whereas anti-TNF treatment in ankylosing spondylitis does not affect the fertility potential. Antisperm antibodies and sulphasalazine treatment in rheumatoid arthritis, as well as mesalazine, infliximab and methotrexate use in inflammatory bowel disease, result in gonadal dysfunction, respectively. More data addressing male fertility are needed for patients with Dermatomyositis, Sarcoidosis, Psoriasis and Celiac disease. Fertility impairment is common in autoimmune diseases. Henceforth, more studies are needed to identify the relationship between fertility and immunity.

Keywords: Autoimmune diseases; Male fertility; Sperm abnormalities; Semen quality; Fertility impairment

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Konstantinos Sfakianoudis, Konstantinos Pantos, Sokratis Grigoriadis, Anna Rapani, Evangelos Maziotis, Petroula Tsioulou, Polina Giannelou, Adamantia Kontogeorgi, Agni Pantou, Nikolaos Vlahos, Michael Koutsilieris, Mara Simopoulou

Purpose This systematic review including a meta-analytical approach aims to investigate the safety and efficacy of employing a double ovarian stimulation (DuoStim) and a subsequent double oocyte retrieval in the same menstrual cycle, in poor ovarian reserve (POR) patients.
Methods A systematic search of literature was performed in the databases of PubMed/MEDLINE, Embase, and Cochrane Central Library up untilMarch 2019. Both prospective and retrospective cohort studies considered suitable for inclusion reported on women with POR undergoing a DuoStim in the follicular (FPS) and luteal phase (LPS) of the same menstrual cycle. Following the systematic review of the literature, a meta-analytical approach was attempted.
Results This study indicates that DuoStimis correlatedwith a higher number of retrieved oocytes,matureMII oocytes, and goodquality embryos in comparison to conventional stimulation. Additionally, LPS seems to be correlated with an equal or an even higher overall performance in comparison to FPS.
Conclusion DuoStim favors an enhanced clinical outcome in regard to the total number of yielded oocytes, mature oocytes, and available embryos, along with the quality of obtained embryos. Sourced data indicate that LPS is not correlated with a higher aneuploidy rate. This option may present as promising for the time-sensitive nature of POR patients’ management, by enabling a higher oocyte yield during a single menstrual cycle.

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Leila Top, Nicolaos Salakos, Michalis Kaloeidas, Georgios Koumantakis, Perilkis Panagopoulos, Efthimios Deligeoroglou

Aim: The aim of this study is to summarize the methods used for contraception from antiquity to nowadays and to highlight the latest ones with their advantages and disadvantages.
Materials and Methods: In order to gather the following data, scientific papers from the PUBMED database, ancient texts, historical data, newer article-searching literature, contraceptive methods and the collection of books of the Family Planning Department of the 2nd Department of Obstetrics & Gynecology of the Aretaieion Hospital.
Results: Contraception is a means of controlling fertility, is an old and sexual function. The history of contraception began with the discovery of the relationship between intercourse and pregnancy. Over the years many contraceptive methods have emerged, involving mechanical components up to the use of pharmaceuticals, and several of them were natural and others were artificial.
Conclusions: Today contraception provides the couples with the opportunity to determine both the time and number of pregnancies. The progress in the decrease of the number of unwanted pregnancies and the provision of contraception with minimal side effects is a collective effort requiring constant collaboration of reliable clinics, scientists and volunteers of clinical trials in combination with the collaboration of the pharmaceutical industry, family planning organizations and the government. The new contraception alternatives are going to improve the opportunities of an appropriate, acceptable contraceptive method by the wider public, eliminating thus birth control failure.

Key Words: Contraception, methods of contraception, history of contraception, new methods of contraception.

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Anastasios Chatziaggelou, Evangelos G. Sakkas , Raffaella Votino, Maria Papagianni , George Mastorakos

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders characterized by defects of adrenal steroidogenesis due to mutations in one of the following enzymes: 21-hydroxylase (21OH), 11b-hydroxylase (11bOH), 17a-hydroxylase (17OH; also known as 17, 20-lyase), 3b hydroxysteroid dehydrogenase type 2 (3bHSD2), steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and P450 oxidoreductase (POR). More than 95% of congenital adrenal hyperplasia cases are due to mutations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme (P450c21). This work focuses on this type of CAH given that it is the most frequent one. This disease is characterized by impaired cortisol and aldosterone production as well as androgen excess. A variant of the CAH is the non-classic type of CAH (NCCAH), usually asymptomatic before the 5th year of age, diagnosed during puberty especially in patients visiting a fertility clinic. NCCAH is characterized mainly by anovulatory cycles and/or high androgen concentrations. Both types of CAH are associated with infertility. Given that the incidence of NCCAH is greater than that of CAH, patients suffering from NCCAH are more often diagnosed for the first time in a fertility clinic. Thus, screening for NCCAH should always be considered. The causes of infertility in CAH patients are multi-factorial including virilization of external genitalia, altered psychosocial development, and hormonal disorders. The main challenges encountered in assisted reproduction are the androgen excess-associated anovulatory cycles as well as the increased circulating progesterone concentrations during the follicular phase which impact endometrial receptivity, tubal motility, and cervical thickness. Administration of sufficient substitution dose of glucocorticoids usually resolves these problems and leads not only to successful assisted reproduction treatment but also to spontaneous pregnancy. Patients with CAH should be followed by a multidisciplinary team including gynecologist, endocrinologist, and pediatrician.

Keywords: infertility, IVF (in vitro fertilization), congenital adrenal hyperplasia (CAH), pregnancy, assisted reproduction (ART)

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Panagiota Papargyri, Evangelia Zapanti, Nicolaos Salakos, Loukas, Papargyris, Alexandra Bargiota & George MASTORAKOS

Abstract

Introduction: In the human organism, a constant interplay exists between the stress system [which includes the activity of the hypothalamic-pituitary-adrenal (HPA) axis] and the adipose tissue. This interplay is mediated by hormones of the HPA axis such as corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and glucocorticoids (GCs) and adipokines secreted by the adipose tissue. Areas covered: In this critical review, the bi-directional interactions between HPA axis and the most studied adipokines such as leptin and adiponectin, as well as the pro-inflammatory adipocytokines tumor necrosis factor (TNF) and interleukin (IL) 6 are presented. Furthermore, these interactions are described in normalcy as well as in specific clinical paradigms of stress-related disorders such as eating disorders, hypothalamic amenorrhea, and stress-related endogenous hypercortisolism states. Wherever new therapeutic strategies emerge, they are presented accordingly. Expert commentary: Additional research is needed to clarify the mechanisms involved in the interplay between the HPA axis and the adipose tissue. Research should be focused, in particular, on the development of new therapeutic means targeting dysfunctional adipose tissue in stress-related situations.

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