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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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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J Obstet Gynaecol, 2021 Oct 25;1-7. doi: 10.1080/01443615.2021.1959534. Online ahead of print.

Ermioni Tsarna, Panagiotis Christopoulos

Abstract: Gestational diabetes mellitus (GDM) is a common metabolic disease associated with maternal and foetal complications; gut microbiome might participate in GDM pathogenesis. Possible biological links include short chain fatty acids, incretin hormones, bile acids homeostasis and peroxisome proliferator-activated receptor gamma deficiency. Gut microbiome differs in patients with GDM even in early pregnancy, but no differences are observed five years postpartum. Patients have enriched Verrucomicrobia phylum, Christensenellaceae and Lachnospiraceae families, Haemophilus, Prevotella, Actinomyces, Collinsella and Ruminococcus genera during pregnancy. Clostridiales order, Alistipes, Faecalibacterium, Blautia, Eubacterium and Roseburia genera are depleted. However, there is great heterogeneity in the reviewed studies and scientific data on the use of gut microbiome characteristics and related biomarkers in GDM risk stratification and diagnosis are scarce. Probiotics and synbiotics have been tested for prevention and treatment for GDM with limited efficacy. Future studies should explore the effect of probiotics administration at first trimester of pregnancy and their value as adjuvant therapy.

Keywords: GDM; Gestational diabetes; gut microbiome; probiotics; synbiotics.

Front. Endocrinol., 02 August 2021 | https://doi.org/10.3389/fendo.2021.714214

Ifigeneia Kassotaki, Georgios Valsamakis, George Mastorakos, Dimitris K. Grammatopoulos

Abstract: Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s hypothalamic–pituitary–adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.

Keywords: Assisted reproductive techniques; Diabetes mellitus; Neonatal complications; Pregnancy outcome.

Hormones (Athens), 2021 Oct 20, doi: 10.1007/s42000-021-00329-8. Online ahead of print.

Christos F Zymperdikas, Vasileios F Zymperdikas, George Mastorakos, Grigorios Grimbizis, Dimitrios G Goulis

Abstract

Objective: To assess maternal and neonatal outcomes in women with or without preexisting diabetes mellitus (DM) undergoing assisted reproduction technology (ART) treatment.
Methods: Prospective or retrospective controlled trials reporting on women with or without preexisting DM undergoing ART treatment were considered eligible. Twelve electronic databases were systematically searched up to December 2020. The risk of bias was assessed by the Cochrane Risk OF Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Each primary outcome was extracted and pooled as maternal- or neonatal-related.
Results: Two studies were included in the systematic review, reporting on both maternal- and neonatal-related parameters after ART treatment. Due to the limited data, no meta-analysis was conducted. Preterm birth, placenta previa, and excessive bleeding during pregnancy were observed more often in pregnancies complicated by preexisting DM conceived by ART compared with pregnancies without DM. There was no difference in the risk for placental abruption between the groups. Regarding the neonatal outcomes, large-for-gestational-age (LGA) embryos and neonatal intensive care unit (NICU) admission were more commonly reported for women with preexisting DM. In one study, preexisting DM was marginally associated with infant mortality.
Conclusions: Despite the scarce data, preexisting DM in pregnancies conceived by ART is associated with increased risk for maternal and neonatal complications.

Keywords: Assisted reproductive techniques; Diabetes mellitus; Neonatal complications; Pregnancy outcome.

D. Metallinou, K. Tzounara, P. Nikolaidis, C. Nanou, A. Lykeridou

Abstract: Disruption of smooth intrauterine brain development is a significant consequence of premature birth that can lead to adverse neurological outcomes. Although noteworthy progress has been made in the management of preterm neonates, rates of neonatal morbidity and neurodevelopmental disorders remain high in this population, underlining the need to find and institute care practices that protect, in particular, the central nervous system (CNS). A promising model of care for premature neonates is “neuroprotective care”, which reduces the sensory and environmental stimuli of the neonatal intensive care unit (NICU), supporting, in this way, the neuroplasticity of the developing neonatal brain. The clinical practices of this model aim to prevent or minimize the presentation of neurodevelopmental disorders. They can be applied by a specialized interdisciplinary team in the NICU, and close cooperation with the family of the neonate in the care plan is crucial.

Key words: Clinical practices, Neuroprotective care, Premature neonate

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J Obstet Gynaecol. 2020 May;40(4):461-467. doi: 10.1080/01443615.2019.1628191. Epub 2019 Jul 29.

Dimitra Metallinou, Katerina Lykeridou, Grigorios Karampas, Georgios Theodoros Liosis, Chrysanthi Skevaki, Myrto Rizou, Ioannis Papassotiriou, Demetrios Rizos

Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENT What is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role. What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL’s ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary.

Keywords: MMP-9/NGAL complex; Milk; NGAL; diabetic pregnancy; lipocalin-2.

Danai Barlampa, Maria Sotiria Bompoula, Alexandra Bargiota, Sophia Kalantaridou ,  George Mastorakos, Georgios Valsamakis

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is a heterogeneous condition characterized by reproductive, endocrine, metabolic, and psychiatric abnormalities. More than one pathogenic mechanism is involved in its development. On the other hand, the hypothalamus plays a crucial role in many important functions of the body, including weight balance, food intake, and reproduction. A high-fat diet with a large amount of long-chain saturated fatty acids can induce inflammation in the hypothalamus. Hypothalamic neurons can sense extracellular glucose concentrations and participate, with a feedback mechanism, in the regulation of whole-body glucose homeostasis. When consumed nutrients are rich in fat and sugar, and these regulatory mechanisms can trigger inflammatory pathways resulting in hypothalamic inflammation. The latter has been correlated with metabolic diseases, obesity, and depression. In this review, we explore whether the pattern and the expansion of hypothalamic inflammation, as a result of a high-fat and -sugar diet, may contribute to the heterogeneity of the clinical, hormonal, and metabolic presentation in PCOS via pathophysiologic mechanisms affecting specific areas of the hypothalamus. These mechanisms could be potential targets for the development of effective therapies for the treatment of PCOS.

Keywords: high-fat diet; nutrients overconsumption; polycystic ovary syndrome; PCOS; hypothalamic inflammation; hypothalamus

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Dimitra Metallinou, Grigorios Karampas, Eleftheria Lazarou, Nikoletta Iacovidou, Panagiota Pervanidou, Katerina Lykeridou, George Mastorakos, Demetrios Rizos

Abstract

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

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Athanasios Chasiotis, Antonios Makrygiannakis, Sophia Kalantaridou, Nikolaos Vrachnis

Abstract

The aim of this systematic review is the collection and presentation of all scientific data to date, regarding the effectiveness of the intrauterine injury in cases of repeated failed attempts of conception, through in vitro fertilization. A systematic review of studies evaluating the association between intrauterine injury and increased fertility in women with recurrent failed IVF attempts was performed, in the databases Medline, PubMed, Embase, Google Scholar and Cochrane Central Registry, with regard to information about the fertility potential of these women. The data of the studies analyzed in the present study, indicate that there is a significant correlation between endometrial injury and increased fertility in women with repeated failed IVF attempts. Hysteroscopy with endometrial tissue damage, or the use of a suction pipette catheter during the menstrual cycle that precedes the ovarian stimulation for a subsequent IVF / ICSI, can highly improve the implantation and clinical pregnancy rates in women with failed IVF attempts. The application of local endometrial injury at the cycle preceding the ovarian stimulation for IVF/ICSI, especially during the luteal phase, seems to enhance the endometrial receptivity to the implanted fetus. The endometrial injury may induce changes in the endometrium that are thought to be able to improve the outcomes of the assisted reproduction efforts. Future RCTs are required in order to establish the integration of this therapeutic approach in ART protocols.

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