Stress urinary incontinence and endogenous sex steroids in postmenopausal women.

AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121-125, 2017. © 2015 Wiley Periodicals, Inc.

Thyroid function and autoimmunity are associated with the risk of vertebral fractures in postmenopausal women.

Overt or subclinical thyroid dysfunction may affect the risk of fragility fractures. The aim of the present study was to assess the association of thyroid function and autoimmunity with vertebral fractures (VF) in a large sample of Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid postmenopausal women, aged 35-79 years. Euthyroidism was verified by serum thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4-4.5 µIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase antibodies (anti-TPO) were compared according to the presence of VFs. Multivariate logistic regression showed that the presence of VFs was predicted independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age, and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312, p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637, p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower circulating TSH had higher risk of having a VF, independently of age, menopausal age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies also indicated an elevated risk of fracture. Levels of thyroid hormones had no apparent effect on the risk of fracture. Further studies are necessary to establish the significance of our findings.

Association of sex hormones and glucose metabolism with the severity of multiple sclerosis.

PURPOSE/AIM OF THE STUDY: We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. MATERIAL AND METHODS: This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. RESULTS: Follicle-stimulating hormone correlated with mean EDSS scores (r = -0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = -0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal-mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. CONCLUSION: Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

OBJECTIVE: To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. INTERVENTION(S): A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. OUTCOME: Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. RESULTS: The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. CONCLUSIONS: AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Indices of adiposity and thyroid hormones in euthyroid postmenopausal women.

OBJECTIVE: We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. DESIGN: Cross-sectional study. METHODS: Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. RESULTS: After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(ß)=0.035, P=0.020 and FT3:FT4, Exp(ß)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(ß)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81 ± 0.62 cm vs 1.54 ± 0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(ß)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, ß=0.259, P=0.040) and women with higher WHR (ß=0.309, P=0.020) but not among women with lower BMI or WHR values. CONCLUSION: Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings.

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study.

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERß)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERß and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERß was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERß and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

Bsm1 vitamin D receptor polymorphism and calcium homeostasis following bariatric surgery.

PURPOSE/AIM: To evaluate the association between the Bsm1 vitamin D receptor polymorphism and the calcium-vitamin D-parathormone axis following bariatric surgery. MATERIALS AND METHODS: This cross-sectional study included 86 morbidly obese patients, who underwent either gastric bypass or sleeve gastrectomy, with a mean follow-up of four years. Calcium metabolism indices and bone turnover markers were assessed according to the presence of secondary hyperparathyroidism and the Bsm1 vitamin D receptor genotypes. RESULTS: Secondary hyperparathyroidism (42.2% of sample) was associated with lower levels of 25hydroxyvitamin D and elevated markers of bone turnover. In subjects without secondary hyperparathyroidism, presence of the unfavorable B allele resulted in higher levels of parathormone (Bb and BB vs. bb genotype: 50.3 ± 8.2 pg/dl vs. 44.4 ± 10.7 pg/dl, p = .011, adjusted for weight loss, baseline body mass index, 25hydroxyvitamin D, surgical procedure, and duration after surgery). In the whole sample, patients bearing the unfavorable B allele exhibited lower weight loss, a parameter that was negatively associated with markers of bone resorption. CONCLUSIONS: Secondary hyperparathyroidism is highly prevalent after bariatric surgery. Bsm1 vitamin D receptor polymorphism may have an effect in early stages of calcium metabolism imbalance, while no association is detected in patients who have already developed secondary hyperparathyroidism. Moreover, vitamin D receptor polymorphism is associated with post-surgery weight loss, a process related to bone turnover.

Vertebral fracture prevalence among Greek healthy middle-aged postmenopausal women: association with demographics, anthropometric parameters, and bone mineral density.

BACKGROUND CONTEXT: The prevalence of skeletal fractures shows a marked geographic variability; however, data regarding the Greek population remain limited. PURPOSE: To evaluate the frequency of asymptomatic vertebral fractures (VFs), and potential risk factors, in a large sample of Greek postmenopausal women. STUDY DESIGN: A cross-sectional study at the University Menopause Clinic. PATIENT SAMPLE: Four hundred fifty-four postmenopausal women aged 35 to 80 years, with an average menopausal age of 9.2±7.1 years. OUTCOME MEASURES: They included medical history, anthropometric and biochemical parameters, bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), and LS lateral radiographs. METHODS: Lumbar spine lateral radiographs were evaluated according to quantitative procedures, aiming to identify VFs. Anthropometric and biochemical parameters and values of BMD were compared according to the presence of VFs. RESULTS: A total of 37 (8.15%) women had at least one VF. Lumbar spine and FN-osteoporosis was identified in up to 23.1% and 40.9% subjects with prevalent VFs, respectively. The prevalence of VFs was largely associated with age, with women aged 60 years or more presenting an up to fourfold risk compared with younger women. Moreover, the presence of VFs was associated with higher menopausal age, advanced age at menarche, a history of early menopause, and prolonged lactation. Lower LS-BMD and, especially, FN-BMD were negatively associated with VF prevalence (prevalent VF vs. no VF: LS-BMD, 0.89±0.16 g/cm(2) vs. 0.98±0.16 g/cm(2), p=.010; FN-BMD, 0.72±0.10 g/cm(2) vs. 0.81±0.12 g/cm(2), p=.008). CONCLUSIONS: Asymptomatic VFs are common among Greek healthy middle-aged postmenopausal women. More than 50% subjects with prevalent VFs present with normal BMD or osteopenia. Age and bone density classification at the FN presented the strongest association with the prevalence of VFs.

Application of Creatsas vaginoplasty after radical surgical treatment of sarcoma botryoides.

BACKGROUND: Sarcoma botryoides of the female genital tract is a rare malignancy. For many years, treatment consisted of radical procedures involving removal of the vagina, cervix, and uterus. Reconstructive surgery is essential for these patients, in order to achieve vaginal penetrative sexual intercourse. CASE: A 17-year-old adolescent, with medical history of surgical excision of uterus and vagina at the age of 2, due to sarcoma botryoides, underwent Creatsas vaginoplasty. A neovagina with adequate dimensions to allow comfortable sexual intercourse was created, without the need for postoperative dilations and without any complications. SUMMARY AND CONCLUSIONS: Creatsas vaginoplasty can be safely performed in patients with medical history of radical pelvic surgery, while other more invasive techniques may carry an increased risk of intra- or postoperative complications.

Hemizona assay and sperm penetration assay in the prediction of IVF outcome: a systematic review.

The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA's role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52-100%), specificity (0-100%), and PPV (18-100%) and NPV (0-100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75-100%), good specificity (57-100%), and high PPV (79-100%) and NPV (68-100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting.

Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor- κ B Ligand, and Subclinical Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus.

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor- κ B ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthy matched controls, were studied with anthropometric and laboratory measurements, including serum OPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P 0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6 mg/dl, P 0.025). Both in the total study population (ß 0.418, P 0.027) and among T1DM patients separately (ß 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPG in both groups (ß -0.335, P 0.003 and ß -0.356, P 0.008 respectively), while sRANKL levels were not associated with any factor. Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear.

Hofbauer cells morphology and density in placentas from normal and pathological gestations.

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction.

BACKGROUND: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 50% of women presenting with subfertility. Subfertility affects 15% to 20% of couples trying to conceive. A significant proportion of these women ultimately need assisted reproductive technology (ART). In vitro fertilisation (IVF) is one of the assisted reproduction techniques employed to raise the chances of achieving a pregnancy. For the standard IVF technique, stimulating follicle development and growth before oocyte retrieval is essential, for which a large number of different methods combining gonadotrophins with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response, characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome. A potentially effective intervention for women with PCOS-related subfertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only data available have derived from observational studies and non-randomised clinical trials. OBJECTIVES: To compare outcomes associated with in vitro maturation (IVM) followed by vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) versus conventional IVF or ICSI, among women with polycystic ovarian syndrome (PCOS) undergoing assisted reproductive technologies (ART). SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials to May 2013 for any relevant trials identified from the title, abstract, or keyword sections. This was followed by a search of the electronic database MEDLINE, EMBASE, LILACS and CINAHL, without language restriction. We also performed a manual search of the references of all retrieved articles; sought unpublished papers and abstracts submitted to international conferences, searched the clinicaltrials.gov and WHO portal registries for submitted protocols of clinical trials, and contacted experts. In addition, we examined the National Institute of Clinical Excellence (NICE) fertility assessment and treatment guidelines and handsearched reference lists of relevant articles (from 1970 to May 2013). SELECTION CRITERIA: All randomised trials (RCTs) on the intention to perform IVM before IVF or ICSI compared with conventional IVF or ICSI for subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Three review authors (CS, MK and NV) independently assessed eligibility and quality of trials. Primary outcome measure was live birth rate per randomised woman. MAIN RESULTS: There were no RCTs suitable for inclusion in the review, although there are currently three ongoing trials that have not yet reported results. AUTHORS' CONCLUSIONS: Though promising data on the IVM technique have been published, unfortunately there is still no evidence from RCTs upon which to base any practice recommendations regarding IVM before IVF or ICSI for women with PCOS. Meanwhile, the results of the above-mentioned ongoing trials are awaited and, of course, further evidence from good quality trials in the field is eagerly anticipated.

Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype.

OBJECTIVE: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. METHODS: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima-media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. RESULTS: Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. CONCLUSION: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.

Hofbauer cells morphology and density in placentas from normal and pathological gestations / Morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

OBJETIVO: Em placentas de gestações sem complicações, as células de Hofbauer desaparecem ou se tornam raras após o quarto ou quinto mês de gestação. Entretanto, a imunohistoquímica revela que uma alta porcentagem de células estromais pertencem às células de Hofbauer. O objetivo do presente estudo foi investigar as alterações da morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas. MÉTODOS: Foram examinadas 70 placentas: 16 provenientes de gestações normais a termo, 10 de abortos espontâneos no primeiro trimestre, 26 de casos diagnosticados como anormalidade cromossômica do feto, e amostras de tecido placentário com complicações causadas pela restrição de crescimento intrauterino (8) ou pelo diabetes mellitus gestacional (10). Cortes corados com hematoxilina-eosina (HE) foram submetidos a estudo histológico e imunohistoquímico utilizando-se os seguintes marcadores: CD 68, lisozima, antiquimotripsina A1, CK-7, vimentina, e Ki-67. RESULTADOS: Em gestações normais a termo, o estudo HE revelou células de Hofbauer em 37,5% dos casos, enquanto a imunohistoquímica as revelou em 87,5% dos casos. Em abortos do primeiro trimestre e em casos de diagnóstico prenatal de anormalidades cromossômicas fetais, tanto o estudo básico como o estudo imunohistoquímico foram positivos para células de Hofbauer. Em gestações complicadas pela restrição de crescimento intrauterino ou pelo diabetes mellitus gestacional, imunoreação positiva foi observada respectivamente em 100 e 70% dos casos. CONCLUSÕES: As células de Hofbauer estão presentes nos vilos placentários durante a gestação, embora com densidade progressivamente reduzida. O marcador mais específico para sua detecção parece ser a antiquimotripsina A1. Vale salientar que atividade mitótica de células de Hofbauer não foi detectada em nosso estudo, uma vez que o marcador de multiplicação celular Ki-67 foi negativo em todas as amostras examinadas.

Addition of prednisolone and heparin in patients with failed IVF/ICSI cycles: a preliminary report of a clinical trial.

Through a non-randomized clinical trial, we examined the theoretical benefit of the coadministration of low molecular weight heparin (LMWH) and prednisolone on pregnancy outcomes in women with previously failed IVF/ICSI cycles. Fifteen women constituted the study group, and were compared with 19 women receiving LMWH alone and another 18 women with no drugs. Our finding that the combination of the two drugs produced positive differences in terms of embryo quality, pregnancy and live birth rates points to the necessity for adequately powered randomized trials.

Granulocyte macrophage colony stimulating factor supplementation in culture media for subfertile women undergoing assisted reproduction technologies: a systematic review.

Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure.

Subclinical atherosclerosis in menopausal women with low to medium calculated cardiovascular risk.

BACKGROUND: The menopausal status is closely related with cardiovascular disease (CVD). Nevertheless, it is still not included in risk stratification by total cardiovascular risk estimation systems. The present study aimed to evaluate the extent of subclinical vascular disorders in young healthy postmenopausal women. METHODS: This cross-sectional study consecutively recruited 120 healthy postmenopausal women without clinically overt CVD or diabetes, aged 41-60 years and classified as not high-risk by the Heartscore (<5%). In addition to risk factors used for Heartscore calculations, years since menopause and associated risk factors (triglycerides (range 37-278 mg/dl), waist circumference (62-114 cm), fasting blood glucose (69-114 mg/dl) and HOMA-IR (0.44-5)) were also assessed. Carotid-femoral pulse wave velocity, carotid and femoral intima-media thickness in the abnormal range as well as atheromatous plaques both in carotid and femoral arteries were used to define the presence of subclinical atherosclerosis. RESULTS: Subclinical atherosclerosis and the presence of at least one plaque were identified in 55% and 28% of women, respectively. Subjects with subclinical atherosclerosis had higher age, years since menopause, HOMA-IR and blood pressure. By multivariate analysis years since menopause and systolic blood pressure independently determined subclinical atherosclerosis while 79% of intermediate-risk women (Heartscore 2-4.9%) being in menopause for at least 4 years would be reclassified to a higher risk for the presence of atherosclerosis. CONCLUSION: Subclinical atherosclerosis was highly prevalent in postmenopausal women with low to medium Heartscore. Thus our data suggest that menopausal status and associated risk factors should be additionally weighted in risk calculations, regarding primary prevention strategies in this population.

Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios.

OBJECTIVE: To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E(2) ratios. DESIGN: Prospective, nonrandomized study. SETTING: Reproductive medicine clinic. PATIENT(S): The study group consisted of 29 infertile men with a low serum T/E(2) ratio (<10). INTERVENTION(S): Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months. MAIN OUTCOME MEASURE(S): Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E(2). In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated. RESULT(S): The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E(2) ratios improved both hormonal and semen parameters. CONCLUSION(S): This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy.