Category Archives: Δημοσιευμένες εργασίες

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Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis

Eirini Papadimitriou, Georgios Boutzios, Alexander G. Mathioudakis, Nikos F. Vlahos, Panayiotis Vlachoyiannopoulos, George Mastorakos

Abstract
Purpose: A systematic review and meta-analysis was conducted comparing the presence of antiphospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.

Methods: Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set.

Results: Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively).

Conclusion: The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.

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The role of maternal physical activity on in vitro fertilization outcomes: a systematic review and meta‑analysis

Eleftheria Kakargia, Eleftherios Mamalakis, Maximos Frountzas, Evangelos  Anagnostou, Charalampos Siristatidis

Abstract
Purpose This systematic review is designed to summarize the evidence concerning the impact of maternal physical activity on the reproductive outcomes following assisted reproduction techniques (ART), namely in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
Methods We searched for eligible studies on PubMed, EMBASE databases and the Cochrane Library from their inception until September 2021. Our primary outcomes were live birth rate and miscarriage, while secondary ones included clinical pregnancy and implantation rates. The quality of the evidence was evaluated using a study-specific adaptation of the Robins I tool.
Results Quantitative data from 10 cohort studies (CS) and 2 randomized control trials (RCT), involving 3431 women undergoing ART treatments, were included in the analyses. The pooled results exhibited uncertainty regarding the effect of physical activity on live birth rate per woman (OR 1.15, 95% CI 0.92–1.43, p = 0.23, I2 = 61%, 9 studies) and miscarriage rates (OR 0.79, 95% CI 0.44–1.43, p = 0.43, I2 = 44%, 6 studies). However, physical activity was associated with significantly improved clinical pregnancy rate after ART (OR 1.39, 95% CI 1.08–1.79, p = 0.0009, I2 = 68%, 10 studies), whereas implantation rate after ART almost reached statistical significance (OR = 1.95, 95% CI 0.99–3.82, p = 0.05, I2 = 77%).
Conclusion The current evidence is still insufficient to firmly conclude on the effect of maternal physical activity on live birth, miscarriage and implantation rates. Although clinical pregnancy rates favored physical activity in this group of patients, these results must be undertaken with caution due to the low quality and the high heterogeneity of the studies included.

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Effect of oral contraceptives on bone mineral density

C. Ampatzis, S. Zervoudis, G. Iatrakis, G. Mastorakos

Abstract
Contraceptives are widely used in our times and a lot of research has been conducted to clarify their impact on Bone Mineral Density. Combined Oral Contraceptives (COCs) may be detrimental to the BMD of adolescents. However, low-dose are more protective than ultra-low-dose COCs. When it comes to premenopause and perimenopause, COCs have no impact on BMD in women with good ovarian function and no estrogen deficiency. In women with impaired ovarian function, it seems that COCs have a positive influence on BMD. Progestin onlypills may not affect BMD, but further research is needed. Depot medroxyprogesterone acetate injection (DMPA) has a negative impact, especially in adolescents, which is duration related but evidence shows that BMD recovers after discontinuation. Levonorgestrel-releasing intrauterine system (LNG-IUS) has no impact on BMD.

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Tools for Quality of Life Assessment during Pregnancy: A Narrative Review

Kyriaki Mitta, Gesthimani Mintziori, George Mastorakos, Eleftheria Taousani, Maria Tzitiridou and Dimitrios G. Goulis

Background: Pregnancy is a period of physiological and hormonal alterations that can decrease the quality of life (QoL). Women’s subjective perception of QoL is clinically relevant for assessing the effectiveness of interventions and identifying susceptibility to depression.Objective: This review aims to identify, present, and critically appraise the assessment tools of QoL during pregnancy.Methods: A narrative review of the English-language literature was conducted through the PubMed, CENTRAL, Scopus, and Google Scholar electronic databases.Conclusion: Several generic instruments have been proposed, such as pregnancy-specific and disease- specific questionnaires concerning common diseases during pregnancy. Plasma, salivary and hair cortisol, inflammatory, genetic and epigenetic biomarkers and gut microbiome have also been investigated as potential indicators of maternal anxiety. Their use can quantify the association between pregnancy-specific anxiety and QoL. Application of validated assessment tools of QoL during pregnancy could improve QoL, maternal health interventions, and early identification of susceptibility to maternal depression.

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The addition of clomiphene citrate to ovarian stimulation protocols for poor responders

Olga Triantafyllidou, Giorgos Sigalos, Laertis Gkoles, Stavroula Kastora, Panagiotis Vakas, Eugenia Batsiou, Nikos Vlahos

Poor ovarian response (POR) is one of the most challenging problems in assisted reproduction. Several strategies have been used to improve pregnancy rates. The use of Clomiphene Citrate (CC) has been shown to improve ovarian stimulation outcomes and decrease gonadotropin requirements in women of advanced reproductive age. However, the combination of CC and gonadotropins to improve pregnancy rates after in IVF in poor responders is still unexplored due to the small number of trials with few participants.
This is a prospective cohort trial involving 12 patients diagnosed with poor ovarian response who underwent ovarian stimulation during the period between June 2015 and September of 2017. All patients were treated with the maximum dose of gonadotropins (hMG, 300 IU/day, hMG group) according to a short gonadotropin/GnRH antagonist protocol. In a subsequent cycle those patients underwent the same stimulation protocol with the addition of 100 mg of CC from day 3 to day 7 (CC-hMG group).
Supplementation with 100 mg of CC resulted in a statistically significant increase in estradiol levels, number of follicles and number of oocytes retrieved, as well as an increase in the number of total embryos available for transfer. Furthermore, a significant reduction was observed in cancellation rates in the CChMG group. Two clinical pregnancies, which resulted in two live births and 3 biochemical pregnancies were achieved in the CC/hMG group.
Furthermore, by employing open-source, biological data we identified a common gene (Estrogen Receptor 1, ESR1) between genetic targets of clomiphene treatment and POR which could explain the benefits of clomiphene in this group of patients.
In conclusion, the addition of CC 100 mg to the stimulation regimen in women diagnosed with POR and previous failed IVF cycles could improve stimulation results, but this study could not demonstrate any benefit in terms of clinical pregnancies and live births. The effectiveness of this treatment requires further investigation.

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The Current Evidence Regarding COVID-19 and Pregnancy: Where Are We Now and Where Should We Head to Next?

Theodoros Kalampokas, Anna Rapani, Maria Papageorgiou, Sokratis Grigoriadis, Evangelos Maziotis, George Anifandis, Olga Triantafyllidou, Despoina Tzanakaki, Spyridoula Neofytou, Panagiotis Bakas, Mara Simopoulou and Nikolaos Vlahos

Abstract: Despite the volume of publications dedicated to unraveling the biological characteristics and clinical manifestations of SARS-CoV-2, available data on pregnant patients are limited. In the current review of literature, we present an overview on the developmental course, complications, and adverse effects of COVID-19 on pregnancy. A comprehensive review of the literature was performed in PubMed/Medline, Embase, and Cochrane Central databases up to June 2021. This article collectively presents what has been so far reported on the identified critical aspects, namely complications during pregnancy, delivery challenges, neonatal health care, potential routes of viral transmission, including vertical transmission or breastfeeding, along with the risks involved in the vaccination strategy during pregnancy. Despite the fact that we are still largely navigating uncharted territory, the observed publication explosion in the field is unprecedented. The overwhelming need for data is undoubtable, and this serves as the driver for the plethora of publications witnessed. Nonetheless, the quality of data sourced is variable. In the midst of the frenzy for reporting on SARSCoV-2 data, monitoring this informational overload is where we should head to next, considering that poor quality research may in fact hamper our attempts to prevail against this unparalleled pandemic outbreak.

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Identification of Genetic Causes in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome: A Systematic Review of the Literature

Varvara Ermioni Triantafyllidi, Despoina Mavrogianni, Andreas Kalampalikis, Michael Litos, Stella Roidi and Lina Michala

Abstract: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition characterizing females with absence of the uterus and part of the vagina. Several genetic defects have beencorrelated with the presence of MRKH; however, the exact etiology is still unknown due to the complexity of the genetic pathways implicated during the embryogenetic development of the Müllerian ducts. A systematic review (SR) of the literature was conducted to investigate the genetic causes associated with MRKH syndrome and Congenital Uterine Anomalies (CUAs). This study aimed to identify the most affected chromosomal areas and genes along with their associated clinical features in order to aid clinicians in distinguishing and identifying the possible genetic cause in each patient offering better genetic counseling. We identified 76 studies describing multiple genetic defects potentially contributing to the pathogenetic mechanism of MRKH syndrome. The most reported chromosomal regions and the possible genes implicated were: 1q21.1 (RBM8A gene), 1p31-1p35 (WNT4 gene), 7p15.3 (HOXA gene), 16p11 (TBX6 gene), 17q12 (LHX1 and HNF1B genes), 22q11.21, and Xp22. Although the etiology of MRKH syndrome is complex, associated clinical features can aid in the identification of a specific genetic defect.

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Progestins and the risk of breast cancer

G. Mastorakos, G. Iatrakis, S. Zervoudis, S. Syropoulou

Abstract
Objectives. The present paper aims to investigate the effects of both progesterone and progestin treatment mainly related to the occurrence of breast cancer in women.
Materials and methods. Extensive systematic bibliographic review of Greek and International articles was conducted through the electronic databases Pubmed, Cinahl, Uptodate, and Google Scholar for the identification of articles related to progesterone, progestins and breast cancer treatment.
Results. Hormone therapy with the use of estrogen alone presents a small increased risk or does not present at all an increased risk of breast cancer. With ORs in some studies below 1.0 in current users for 3 plus years and safe option until 7 years, while in other studies the risk was increased with the ORs 1.29. However, the use of estrogen in combination with progestogens, depending on the type of progestogens, shows an increased risk of breast cancer, with the ORs to vary between 1.14- 2.38 from 3 to 5 years and is inversely proportional to the time of its use. This risk varies depending on the combination of the preparations. Other factors that are associated with breast cancer risk when receiving hormone therapy are the years that hormone therapy is taken, directly proportional to the risk. At higher risk are older women, women with low body mass index in menopause (BMI <25kg/m2) and women with increased mammographic breast density. Continued use of hormone therapy is associated with an increased risk for breast cancer compared to sequential. The risk became visible sooner to women who used in the past hormone therapy and were using it again. Starting hormone therapy in the immediate postmenopausal period also increased the risk for breast cancer. Hormone therapy was associated with tumors with positive estrogen and progesterone receptors, and also the lobular histological type was associated with its use. Tibolone use was associated with an increased risk.

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Severe hypovitaminosis D in pregnant refugees arriving in Europe: neonatal outcomes and importance of prenatal intervention

Anna Liori, Damaskini Polychroni, Georgios K Markantes, Maria Stamou, Sarantis Livadas, George Mastorakos and Neoklis Georgopoulos

Abstract: Adequate vitamin D levels are particularly important in pregnant women for both maternal and neonatal health. Prior studies have shown a significantly hi gh prevalence of vitamin D deficiency (VDD) among refugees. However, no study has addressed the prevalence of VDD in pregnant refugees and its effects on neonatal health. In this study, we examined the prevalence of VDD in refugee pregnant women living in Greece an d compared our results with Greek pregnant inhabitants. VDD was frequent in both group s but was significantly more common in refugees (92.2 vs 67.3% of Greek women, P = 0.003) with 70.6% of refugees having severe hypovitaminosis D (<10 ng/mL). As a resu lt, most newborns had VDD, which affected refugee newborns to a greater extent. Our re sults suggest a need to screen newcomer children and pregnant women for VDD in all host countries around the world. Such a screen will appropriately guide early and effectiv e interventions with the goal to prevent adverse neonatal and maternal outcomes.

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Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea

Aikaterini Kapama, Dimitrios T. Papadimitriou, George Mastorakos, Nikolaos F. Vlahos and Maria Papagianni

Abstract: Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.

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