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Objective: Fetal growth restriction is associated with increased postnatal cardiovascular morbidity. The alterations in heart physiology and structure caused by in utero nutrient deprivation have not been extensively studied. We aim to investigate the impact of maternal food restriction on the cardiac proteome of newborn rats with normal (non-fetal growth-restricted (FGR)) and reduced (FGR) birth weight. Methods: On day 14 of gestation, 10 timed pregnant rats were randomized into two nutritional groups: (a) Standard laboratory diet and (b) 50% global food restriction. Pups born to food-restricted mothers were subdivided, based on birthweight, into fetal growth-restricted (FGR) and non-FGR, while pups born from normally nourished mothers were considered controls. Rat neonates were euthanized immediately after birth and the hearts of 11 randomly selected male offspring (n = 4 FGR, n = 4 non-FGR, n = 3 control group) were analyzed using quantitative proteomics. Results: In total, 7422 proteins were quantified (q < 0.05). Of these, 1175 were differentially expressed in FGR and 231 in non-FGR offspring vs. control with 151 common differentially expressed proteins (DEPs) between the two groups. Bioinformatics analysis of DEPs in FGR vs. control showed decreased integrin and apelin cardiac fibroblast signaling, decreased muscle contraction and glycolysis, and over-representation of a protein network related to embryonic development, and cell death and survival. Conclusion: Our study illustrates the distinct proteomic profile of FGR and non-FGR offspring of food-restricted dams underlying the importance of both prenatal adversities and birth weight in cardiac physiology and development. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: The present study aimed to assess the association between ovarian volume and demographic and anthropometric parameters, as well as sex hormones and bone mineral density (BMD) in postmenopausal women. Methods: 161 healthy postmenopausal women participated in this cross-sectional study. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Anthropometric parameters included body mass index (BMI) and waist-to-hip ratio (WHR). Ultrasonography was used to estimate the average ovarian volume for each participant. BMD was measured in the femoral neck (FN) and the lumbar spine (LS) using DXA. Results: Mean ovarian volume increased linearly with increasing quartiles of BMI (Q1:0.985±0.25, Q2: 1.11±0.29, Q3: 1.07±0.28, Q4: 1.19±0.38, p-value for linear trend 0.013). Ovarian volume correlated positively with BMI (r=0.128, p-value=0.038), FN BMD (r=0.233, p-value=0.003), FN T-score (r=0.223, p-value=0.004) and FN Z-score (r=0.171, p-value=0.027). Multivariate analysis showed that ovarian volume was predicted by WHR (b-coefficient=0.157, p-value=0.047) and SHBG (b-coefficient= -0.160, p-value=0.042), independently of age and BMI. Finally, FN BMD was predicted by ovarian volume, independently of age, menopausal age and BMI. Conclusion: Ovarian volume was positively and independently associated with adiposity indexes and femoral BMD in postmenopausal women. Lower SHBG levels were associated with higher ovarian volume. Insulin resistance may mediate these results. The significance of these findings should be assessed in larger prospective studies.

Objective: To explore differences in irisin concentrations between lean adolescents with PCOS and age- and body mass index (BMI)-matched controls and examine the associations of irisin with core features of the syndrome. Design: Cross-sectional study. Patients: Lean females with PCOS, aged 13-21 years. Measurements: Physical, hormonal and sonographic assessment. Irisin concentrations were measured with ELISA. Results: Participants included in total 39 sedentary females (mean ± SD; age 17.3 ± 2.1 years, BMI 20.7 ± 1.3 Kg/m2), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to controls had significantly elevated concentrations of fasting serum irisin (mean ± SD; PCOS, 1.7 ± 1.0 μg/mL vs controls, 1.0 ± 0.4 μg/mL; P =.007), luteinizing hormone (LH), oestradiol, testosterone, Δ4-androstenedione, 17-hydroxyprogesterone, glucose, as well as free androgen index, Ferriman-Gallwey score and mean ovarian volume (MOV). For the total sample, circulating irisin was positively correlated with MOV (r =.332, P =.041), glucose (r =.428, P =.007), insulin (rs =.369, P =.021) and HOMA-IR (rs =.422, P =.007) and negatively correlated with QUICKI (r = −.329, P =.041). Follicle-stimulating hormone (B = 0.295, Beta =.342, P =.042) and MOV (B = 0.182, Beta = 0.821, P =.001) were positive predictors, and LH (B = −0.108, Beta = −0.523, P =.010) and testosterone (B = −0.431, Beta = −0.457, P =.032) were negative predictors of irisin concentrations, whereas irisin positively predicted fasting glucose (B = 0.262, Beta = 0.428, P =.007). In the PCOS group, irisin concentrations were positively correlated with HOMA-IR (rs =.416, P =.048) but negatively correlated with LH (rs = −.499, P =.015), testosterone (r = −.585, P =.003), free androgen index (r = −.426, P =.048) and Ferriman-Gallwey score (r = −.533, P =.015). Conclusions: Irisin was associated with the adolescents' metabolic and reproductive characteristics and the hyperandrogenic phenotype of the syndrome. Much research is needed to ascertain mechanisms of elevated serum irisin in adolescent PCOS. © 2018 John Wiley & Sons Ltd

Objective: To describe two clinical cases concerning patients at risk of developing severe ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) stimulation. Design: Description of clinical management and outcomes of patients using an IVF antagonist rescue protocol to prevent OHSS. Setting: Reproductive medicine unit, University Hospital. Materials and Methods: Two infertile patients undergoing controlled ovarian stimulation (COS) for IVF/intracytoplasmic sperm injection (ICSI) presenting with high risk of OHSS. IVF/ICSI patients following COS under short protocol and high risk of OHSS were managed by withdrawing the aganist and replacing it with an antagonist and triggering ovulation with an agonist bolus. Main outcome measures included incidence of OHSS, oocytes retrieved, and pregnancy rates. Results: None of the two patients developed OHSS. None of the patients had metaphase II retrieved oocytes at oocyte retrieval. Conclusions: Use of COS with short protocol in an IVF/ICSI cycle carrics a risk of severe OHSS. Rescuing the cycle by withdrawing the agonist and replacing it with an antagonist and triggering ovulation with an agonist bolus is not always effective and should not be used if short time interval between agonist replacement with antagonist and ovulation triggering is available.

Introduction: Compared to laparotomy, laparoscopy has many benefits for patients, such as shorter recovery and lower morbidity rates. Port site metastases after laparoscopic approach in the treatment of gynecologic malignancies are uncommon. The purpose of this review is to identify and summarize possible risk factors for port-site metastases in patients undergoing laparoscopic surgery in the ambit of gynecologic oncology. Discussion: The precise incidence of port-site metastases is not well known because many patients are not followed-up during the whole postoperative period. Possible risk factors that can increase the risk of port-site metastases can be the presence of large masses in the abdomen, especially in the presence of concomitant ascites and in patients treated for ovarian carcinomas. Different theories have been postulated in order to explain the development of port site metastases during laparoscopy for oncological patients. Conclusions: Patient selection is an essential factor that can influence the incidence of port site metastases in gynecological patients. Robust data regarding port site metastases in gynecologic oncology are needed.

Objective: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups.Methods: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE).Results: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (p < 0.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR.Conclusions: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain. © 2015 Taylor & Francis.

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R-2 = 0.0679, p = 0.01). IL-6 was increased (p = 0.001) in the GDM group (median = 2 pg/ml) compared to the control group (median = 1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r = -0.3382, p < 0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR) = 59.4 %; for 25 % False Positive Rate (FPR); Area Under the Curve (AUC) = 0.7291; Model R-2 = 0.1096, p < 0.001]. IL-6 alone was a significant predictor of GDM (DR = 51.3 %; for 25 % FPR; AUC = 0.6731; Model R-2 = 0.0616, p < 0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR = 67.5 %; for 25 % FPR; AUC = 0.7586; Model R-2 = 0.1521, p < 0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

Objective: To determine whether in vitro fertilization (IVF), frozen replacement cycles offer better outcomes than fresh cycles in order to support, or not, a possible shift towards total replacement of fresh IVF/intracytoplasmic sperm injection (ICSI) cycles from frozen elective transfers (FETs). Study design: Systematic review; opinion paper. Results: Initial results seem to support a shift in current practice towards frozen cycles. Conclusion: Initial results may support replacement all fresh IVF/ICSI cycles with FETs, as this could be a safer and equally effective strategy. However, robust evidence from randomized controlled trials is needed if this will be generally applied.

The most frequent ovarian germ cell tumors are mature cystic teratomas (MCTs), composing 10-25% of all ovarian neoplasms. MCTs have the potential of undergoing malignant transformation, typically in postmenopausal women, with a frequency of 0.17-3%, with squamous cell carcinoma being the most common malignant tumor arising from MCT. We present the rare clinical entity of a squamous cell carcinoma arising from a mature cystic teratoma in a 56-year-old premenopausal woman as well as diagnostic and therapeutic route followed. © 2014, CIC Edizioni Internazionali, Roma.

Objectives To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. Methods A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. Results Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. Conclusions Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis. © 2013 International Menopause Society.

Aim Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. Method A total of 105 healthy postmenopausal women (aged 4568 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17β-estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 03). Results Concerning endogenous hormones, higher Δ4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). Conclusion Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis. © 2012 International Menopause Society.

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements. © 2012 Informa UK, Ltd.

Objectives To evaluate the effect on breast density of two low-dose hormone therapy regimens identical in their estrogen component but different in the progestin. Methods A total of 81 non-hysterectomized postmenopausal women were allocated either to 17β-estradiol 1 mg and norethisterone acetate 0.5 mg E2NETA, n 43 or to 17β-estradiol 1 mg and drospirenone 2 mg E2DRSP, n 38. Treatment was continuous and lasted 12 months. The main outcomes were the changes in breast density according to the Wolfe classification between baseline and 12-month mammograms. Results Involution of the fibroglandular tissue was not seen in either of the treatment groups. Under E2NETA, breast density increased in seven women 16.3. In contrast, only three women 7.9 exhibited a density increase under E2DRSP. Conclusions Although hormone therapy appears to suspend breast involution, it does not increase breast density in the majority of treated women. Progestins differing in pharmacological properties may have a variable impact on breast density. © 2009 International Menopause Society.

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Δ4-androstendione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21-0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Δ4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD. © Springer-Verlag Tokyo 2006.

Objectives: To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. Methods: The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. Results: No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. Conclusion: Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness. © 2005 Elsevier Ireland Ltd. All rights reserved.

Objective: To present a new imaging technique for the evaluation of the functional effectiveness of Creatsas vaginoptasty. Method: Eighteen women with Mayer-Rokitansky-Kuster-Hauser syndrome underwent a transabdominal and transperineal ultrasound examination 4 weeks and 6 months after the surgical creation of a neovagina, and then yearty, with a condom filled with water as a distending and imaging medium. The functional length and width of the neovagina and its axis deviation were assessed, as well as the postoperative quality of the women’s sexual life. Results: A functional vagina 10 to 12 cm in length and 4 to 5 cm in width was observed; its axis deviation, which was similar to the anatomic deviation, was easily determined; and 94.5% of the women reported a satisfactory white 5.5% reported an adequate sexual life. Conclusion: This new imaging technique is a simple and effective alternative for the evaluation of the postoperative effectiveness of colpopoiesis. (c) 2005 International. Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The possibility of reversing the hypoxanthine induced 2-cell block in mouse embryos when cultured in conditions supplemented with compounds that increase (FSH, hMG, IBMX, hCG) or inhibit (GnRH-analogue) cAMP was assessed. When embryos were cultured in Ham’s F-10 without hypoxanthine supplemented with each of the above compounds, no inhibition of blastocyst development was observed. Embryos were then cultured in Ham’s F-10 with hypoxanthine supplemented again with each compound. For the addition of GnRH-analogue or FSH, the rate bf blastocyst formation was comparable with that of the control medium with hypoxanthine alone. Instead, the addition of IBMX or hMG reversed the induced block. There was no reversible effect for the addition of 2 mu g/ml hCG while the latter was observed with higher doses. The results from GnRH-analogue and IBMX addition show that, contrary to what was found for oocytes, stimulation of cAMP reverses the hypoxanthine-induced block in mouse embryos. FSH and hCG also had effects opposite to those observed for oocytes. It is unknown why hMG (FSH + LH) reverses the block, A lower cAMP degradation rate resulting in a higher cAMP level is a possible explanation. Our results provide further evidence that cleavage arrest by hypoxanthine has a different mechanism than the hypoxanthine-induced arrest of meiosis.

The progesterone antagonist mifepristone (RU486), was given in mice once on different days of pregnant mare’s serum gonadotrophin-human chorionic gonadotrophin (PMSG-HCG) treatment and its action upon the induction of ovulation studied. RU486 administered on the day after PMSG significantly reduced the ovulation rate. Ovulation was completely inhibited when the progesterone antagonist was given simultaneously with HCG, but RU486 administered 4 h after HCG treatment remained ineffective. The development of two-cell zygotes harvested on day 2 post-coitum from mice treated with RU486 on the day after the PMSG treatment was followed in vitro and showed a significant decrease in the number of embryos developing to blastocysts. These results favour the involvement of progesterone in the ovulation process, indicating a direct effect of this hormone at the ovarian level via a progesterone receptor-mediated action.