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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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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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Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males[:]

C E L L  B I O L O G Y

Maria Apostolopoulou, Lucia Mastrototaro, Sonja Hartwig, Dominik Pesta, Klaus Straßburger, Elisabetta de Filippo, Tomas Jelenik, Yanislava Karusheva, Sofiya Gancheva, Daniel Markgraf, Christian Herder, K. Sreekumaran Nair, Andreas S. Reichert , Stefan Lehr, Karsten Müssig, Hadi Al-Hasani, Julia Szendroedi , Michael Roden

High-intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impact on metabolism remains unclear. We hypothesized that 12-week HIIT increases insulin sensitivity in males with or without type 2 diabetes [T2D and NDM (nondiabetic humans)]. However, despite identically higher VO2max, mainly insulin-resistant (IR) persons (T2D and IR NDM) showed distinct alterations of circulating small extracellular vesicles (SEVs) along with lower inhibitory metabolic (protein kinase Cε activity) or inflammatory (nuclear factor κB) signaling in muscle of T2D or IR NDM, respectively. This is related to the specific alterations in SEV proteome reflecting down-regulation of the phospholipase C pathway (T2D) and up-regulated antioxidant capacity (IR NDM). Thus, SEV cargo may con-tribute to modulating the individual metabolic responsiveness to exercise training in humans.

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Ανατολή Πετρίδου

Η Ανατολή Πετρίδου είναι εργαστηριακό και διδακτικό προσωπικό στο Τμήμα Επιστήμης Φυσικής Αγωγής και Αθλητισμού (ΤΕΦΑΑ) Θεσσαλονίκης του Αριστοτέλειου Πανεπιστημίου Θεσσαλονίκης (ΑΠΘ) στο γνωστικό αντικείμενο «Εργαστηριακές εφαρμογές στην αξιολόγηση της βιολογικής απόδοσης του ανθρώπου». Είναι απόφοιτος του ΤΕΦΑΑ του ΑΠΘ και του Τμήματος Βιοχημείας και Βιοτεχνολογίας του Πανεπιστημίου Θεσσαλίας.

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Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Hormones (Athens) 2022 May 6. doi: 10.1007/s42000-022-00370-1. Online ahead of print.

Areti Mina, Georgios Boutzios, Ioannis Papoutsis, George Kaparos, Panagiotis Christopoulos, Eleni Kousta, Minas Mastrominas, Sotirios Athanaselis, George Mastorakos
PMID: 35524040, DOI: 10.1007/s42000-022-00370-1

Abstract: Purpose | Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. Methods | This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. Results | The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. Conclusion | FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

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Απονομή του τίτλου του επισκέπτη καθηγητή της Ιατρικής Σχολής ΕΚΠΑ

Το Δ.Π.Μ.Σ. «Έρευνα στη Γυναικεία Αναπαραγωγή» ανακοινώνει την απονομή του τίτλου του Επισκέπτη Καθηγητή της Ιατρικής Σχολής ΕΚΠΑ στους κάτωθι καθηγητές-συνεργάτες του προγράμματος:

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Uterine sparing management in patients with endometrial cancer: a narrative literature review

Journal of Obstetrics and Gynaecology

Maria Zisi, Dimitrios Zygouris, Orestis Tsonis, Sofia Papadimitriou, Mastorakos George, Sophia Kalantaridou& Minas Paschopoulos

Abstract: Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg–320 mg for MA and 250 mg–600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo–oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient’s age and whether they fulfil the strict criteria selection.

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Major histocompatibility complex(mhc) molecules identification in vaginal cells during menstrual cycle

GYNECOLOGY AND OBSTETRICS

Socrates Megoulas, Savvidi Amalia, Stelios Fiorentzis and Mihail Tziolas

Abstract: Causes of subfertility in women are under investigation, with the vaginal canal being the first barrier before the fertilization and implantation process. Although the mechanisms of protection of the allogeneic fetus from the maternal immune response seem to have a main role through the preimplantation period, they are not yet described in detail. There appears to be an important relation between them and the polymorphism of major histocompatibility complex (MHC) proteins. However, it is unknown which are expressed in the vaginal canal cells and how they behave during the menstrual cycle. This clinical research aimed to prove the existence of these unusual MHC proteins in vaginal cells, especially during ovulation. We selected women of reproductive age in different menstrual cycle phases and collected vaginal samples. The samples then were processed with immunofluorescence protocol or ELISA protocol techniques. The protein molecules that were calculated are MHCI, MHCII, TCRa b, TCRg d. During ovulation, MHCII and TCRg d were expressed in higher numbers over MHCI and TCRa b (p=0.0461, p=0.0104), using immunofluorescence. Whereas using ELISA showed statistical significance only in the expression of TCRg d over TCRa b (p=0.0012). Managing to identify the existence of polymorphic molecules of the immune system in the vagina proves the immunological reaction starts taking place in the vagina, and there is possibly a relation between the immunosuppression mechanisms surrounding trophoblast implantation and early pregnancy success. As the research progresses, it is possible to trace those mechanisms back to subfertility cases.

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