Physical and Sedentary Activities in Association with Reproductive Outcomes among Couples Seeking Infertility Treatment: A Prospective Cohort Study.

BACKGROUND: The aim of this study was to investigate the association of physical activity (PA) with assisted reproductive technology (ART) treatment and pregnancy outcomes among couples seeking infertility treatment. METHODS: This prospective cohort study was carried out among 128 infertile individuals (64 couples), entering the infertility clinic for ART procedures. Baseline PA (before entering any treatment) was assessed using accelerometry for both women and men. For every couple the infertility treatment outcomes were recorded. RESULTS: The couples that required invasive ART procedures such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) spent less time in vigorous PA (-73 min/week per couple, woman + man) than those couples who became spontaneously pregnant after entering the study (p = 0.001). We observed no significant associations between the time spent in physical activities and positive pregnancy test or live birth. CONCLUSIONS: Our results do not support a positive nor negative relation between the time the couples spent in physical activities and the chances of getting pregnant or having a baby among patients seeking infertility treatment. However, couples undergoing invasive ART procedures did less vigorous PA than couples that became spontaneously pregnant, suggesting that PA may interfere with their reproductive health.

Women's experiences of miscarriage related to diagnosis, duration, and type of treatment.

INTRODUCTION: Women with miscarriage experience several negative emotional feelings such as grief, isolation, coping, and despair. However, less is known about how the type of treatment and diagnosis of miscarriage influence the emotional experience. MATERIAL AND METHODS: The present study was a randomized prospective longitudinal cohort study, in which women with spontaneous miscarriage (n = 35), and women with missed miscarriage (n = 67), were included to answer three validated questionnaires: Revised Impact of Miscarriage Scale, Perinatal Grief Scale, and Montgomery and Åsberg Depression Rating Scale, concerning experience of miscarriage, psychological well-being, and mental health 1 week and 4 months after finalized treatment. RESULTS: There was no difference between the 2 diagnosis groups in feelings as measured by Revised Impact of Miscarriage Scale, Montgomery and Åsberg Depression Rating Scale, and Perinatal Grief Scale 1 week after the miscarriage. However, the psychological well-being improved significantly 4 months after the miscarriage. Separated by treatment, women treated with misoprostol alone had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration. CONCLUSIONS: It can be concluded that diagnosis of miscarriage had limited influence on the experiences of miscarriage, but shorter duration of treatment with misoprostol and subsequent vacuum aspiration resulted in fewer depressive symptoms.

Hyaluronan-binding protein 2 (HABP2) gene variation in women with recurrent miscarriage.

BACKGROUND: Idiopathic recurrent miscarriage, defined as three or more consecutive miscarriages, is a distressing early pregnancy complication. Although, the etiology of recurrent miscarriage is still unknown, an aberrant regulation of the endometrial receptivity marker hyaluronan-binding protein 2 (HABP2) has been suggested. The objective of the present study was to investigate the effect of genetic variations of HABP2 in women with idiopathic recurrent miscarriage compared to fertile women. METHODS: This study was designed as a case-control study. In total, 165 women who had three or more consecutive miscarriages and 289 fertile women were included in the study. Polymorphisms in the HABP2 gene were analyzed using TaqMan SNP Genotyping Assays. Three polymorphisms in the HABP2 gene, rs1157916, rs2240879 and rs7080536 (Marburg I) were studied. RESULTS: Polymorphism in HABP2 showed no significant difference in women with recurrent miscarriage compared to fertile women, except for rs1157916 minor A allele that was more prevalent among RM patients (p = 0.058). Significantly higher live birth rate was observed among women with three to four miscarriages compared to those with more miscarriages (p = 0.001). CONCLUSIONS: Variations in the HABP2 gene did not seem to be involved in the etiology of recurrent miscarriage, while, the number of previous miscarriages had an impact on the live birth rate.

Longitudinal study of emotional experiences, grief and depressive symptoms in women and men after miscarriage.

OBJECTIVE: Although miscarriage is common and affects up to 20% of pregnant women, little is known about these couples' short term and long term experiences after miscarriage. The aim of the present study was to study emotional experience, grief and depressive symptoms in women and men, one week and four months after miscarriage. RESEARCH DESIGN /SETTING: Women, (n = 103), and their male partner (n = 78), were recruited at the gynecological clinic after miscarriage. Control women were recruited from the general population. Three validated questionnaires concerning psychological wellbeing and mental health, RIMS, PGS and MADRS-S were answered by the participants one week and four months after the miscarriage. FINDINGS: It was shown that for women, the emotional experiences of miscarriage, grief and depressive symptoms were more pronounced than for their male partners. Grief and depressive symptoms were reduced with time, which was not the case for the emotional experiences of miscarriage. Previous children was favorable for emotional experience while previous miscarriage or infertility treatment made the emotional experience worse. CONCLUSION: Grief and depressive symptoms is reduced over time while emotional experiences such as isolation, loss of baby and a devastating event persist for longer time than four months. Lack of previous children, previous miscarriage and infertility diagnosis could increase negative emotional experiences after miscarriage, this was especially pronounced for grief reaction. The questionnaires could be used both clinically and in research to understand the emotional experiences after miscarriage.

HRG C633T polymorphism and risk of gestational hypertensive disorders: a pilot study.

BACKGROUND: Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders. METHODS: It was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP. RESULTS: The genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04-2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity. CONCLUSIONS: The HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.

Validation of the Revised Impact of Miscarriage Scale for Swedish conditions and comparison between Swedish and American couples' experiences after miscarriage.

INTRODUCTION: There is a lack of knowledge in women's and men's experience of miscarriage. The Revised Impact of Miscarriage Scale (RIMS) has been used in United States to measure the experiences after miscarriage. The first objective was to test the consistency of RIMS for Swedish conditions. The second purpose of this study was to compare Swedish and American couples' experience of miscarriage by use of the RIMS. METHODS: Forward and back translation was used for translating RIMS into Swedish. This is a hospital-based comparative study including Swedish couples (n = 70) and American couples (n = 70). The couples were matched by the women's age, week of miscarriage and number of children. All participants answered socio-demographic, fertility and depression-scale questions in addition to RIMS. RESULTS: Cronbach's alpha analysis was above 0.650, the mean value was 0.824. There was no significant difference between the Swedish and American participants on the factors 'Isolation/Guilt' and 'Devastating event', but the Swedish women and men scored significantly lower on the factor 'Loss of baby' than the American women and men. The men, Swedish and American combined, scored lower than the women in all factors but the correlation within the couples was similar for both Swedish and American couples. CONCLUSIONS: The high consistency between the countries suggests that the RIMS questionnaire is reliable for both women and men to be used in both countries and two of three factors were similar between the two countries.

Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

BACKGROUND: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. MATERIALS AND METHODS: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. RESULTS: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. CONCLUSIONS: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

Compliance to the recommended use of folic acid supplements for women in Sweden is higher among those under treatment for infertility than among fertile controls and is also related to socioeconomic status and lifestyle.

Background: Folate has been discussed in relation to fertility among women, but studies on women under treatment for infertility are lacking. Objective: The objective of this study was to investigate folic acid supplement use and folate status among women under treatment for infertility (hereafter infertile) and fertile women also in regard to socioeconomic and lifestyle factors. Design: Lifestyle and dietary habits, and use of dietary supplements were assessed using a questionnaire. Blood samples were obtained for analysis of folate status. 24-hour recall interviews were also performed. Results: Highly educated, employed and infertile women were most prone to using folic acid supplements. The infertile women had a significantly better folate status than the fertile women. Folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and were employed. Our questionnaire data had only fair agreement with the data from 24-hour recalls, but the folate status data was clearly correlated to our questionnaire results. Conclusions: Infertile women were most prone to using folic acid supplements and had better folate status than the controls. High educational and employment status were found to be key factors for high compliance to the recommended use folic acid supplements.

Effect of Lignocaine on IL-6, IL-8, and MCP-1 in Peritoneal Macrophages and Endometriotic Stromal Cells.

OBJECTIVE: The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells. DESIGN: Experimental in vitro study on human cells. POPULATION AND SAMPLE: Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons. METHODS: Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs. RESULTS: The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls ( P = .028 and P = .018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines ( P = .043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment. CONCLUSION: Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.

Stanniocalcin-1 expression in normal human endometrium and dysregulation in endometriosis.

OBJECTIVE: To determine expression of stanniocalcin-1 (STC1) in human endometrium with and without endometriosis and its regulation by steroid hormones. DESIGN: Laboratory study. SETTING: University. PATIENT(S): Nineteen women with endometriosis and 33 control women. INTERVENTION(S): Endometrial biopsy and fluid sampling. MAIN OUTCOME MEASURE(S): Analysis of early secretory (ESE) and midsecretory (MSE) endometrial secretomes from fertile women with the use of nano-liquid chromatography-dual mass spectrometry; real-time quantitative polymerase chain reaction, and immunohistochemistry for STC1 and its receptor calcium-sensing receptor (CASR) mRNA and proteins in endometrium with and without endometriosis; evaluation of STC1 and CASR mRNA expression in endometrial stromal fibroblasts (eSF) from women with and without endometriosis decidualized with the use of E2P or 8-bromo-cyclic adenosine monophosphate (cAMP). RESULT(S): STC1 protein was strongly up-regulated in MSE versus ESE in endometrial fluid of fertile women. STC1 mRNA significantly increased in MSE from women with, but not from those without, endometriosis, compared with proliferative endometrium or ESE, with no significant difference throughout the menstrual cycle between groups. STC1 mRNA in eSF from control women increased >230-fold on decidualization with the use of cAMP versus 45-fold from women with endometriosis, which was not seen on decidualization with E2/P. CASR mRNA did not exhibit significant differences in any condition and was not expressed in isolated eSF. STC1 protein immunoexpression in eSF was significantly lower in women with endometriosis compared with control women. CONCLUSION(S): STC1 protein is significantly up-regulated in MSE endometrial fluid and is dysregulated in eutopic endometrial tissue from women with endometriosis. It is likely regulated by cAMP and may be involved in the pathogenesis of decidualization defects.

Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer.

Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).

Vaginal Gene Expression During Treatment With Aromatase Inhibitors.

BACKGROUND: Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. PATIENTS AND METHODS: Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. RESULTS: The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. CONCLUSION: In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation.

Physical activity, fatness, educational level and snuff consumption as determinants of semen quality: findings of the ActiART study.

In this study, the association between physical activity and other potential determinants, objectively measured by accelerometry, was examined. Sixty-two men attending an infertility clinic participated in the study. Obese men (body mass index ≥ 30) and those with a waist circumference 102 cm or more had lower semen volume than the other men (P < 0.05). Higher values in sperm parameters were observed in participants who completed university studies and those who did not consume snuff, compared with the other participants (P < 0.05). Finally, men who spent an average number of 10 min-bouts of moderate-to-vigorous physical activity had significantly better semen quality than those who engaged in low or high numbers of bouts of activity (P < 0.05). No associations were found for sedentary or moderate-to-vigorous physical activity time when it was not sustained over 10 min, i.e. not in bouts. Men who have average levels of physical activity over sustained periods of 10 min are likely to have better semen quality than men who engage in low or high levels of such activity. Similarly, high levels of total and central adiposity, low educational level and snuff consumption are negatively related to semen quality.

Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to in vitro fertilization pregnancy outcome.

OBJECTIVE: To study folic acid intake, folate status and pregnancy outcome after infertility treatment in women with different infertility diagnoses in relation to methylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C and 1793G>A polymorphisms. Also the use of folic acid supplements, folate status and the frequency of different gene variations were studied in women undergoing infertility treatment and fertile women. DESIGN: Observational study. SETTING: University hospital. POPULATION: Women undergoing infertility treatment and healthy, fertile, non-pregnant women. METHODS: A questionnaire was used to assess general background data and use of dietary supplements. Blood samples were taken to determine plasma folate and homocysteine levels, and for genomic DNA extraction. A comparison of four studies was performed to assess pregnancy outcome in relation to MTHFR 677 TT vs. CC, and 1298 CC vs. AA polymorphisms. MAIN OUTCOME MEASURES: Folic acid supplement intake, and plasma folate, homocysteine and genomic assays. RESULTS: Women in the infertility group used significantly more folic acid supplements and had better folate status than fertile women, but pregnancy outcome after fertility treatment was not dependent on folic acid intake, folate status or MTHFR gene variations. CONCLUSION: High folic acid intakes and MTHFR gene variations seem not to be associated with helping women to achieve pregnancy during or after fertility treatment.

Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion.

Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.

The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage: a pilot study.

BACKGROUND: Histidine-rich glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage. METHODS: The study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. RESULTS: The results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p<0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p<0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p<0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p<0.05). CONCLUSIONS: Women who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.

Bisphenol A affects human endometrial endothelial cell angiogenic activity in vitro.

The widespread Bisphenol A (BPA) is classified as an endocrine-disrupting chemical (EDC) with estrogenic properties. Human endometrial endothelial cells (HEECs) play a key role in the endometrial angiogenesis that is under the control of estradiol. The hypothesis was that BPA may affect endometrial angiogenesis by disturbing some functional properties of the HEEC. To study this, primary HEECs were exposed to environmentally relevant doses of BPA. The HEECs were co-cultured with primary endometrial stromal cells to create conditions as similar to the in vivo situation as possible. The effects of BPA were evaluated by proliferation and viability assays, tube-formation assays, quantitative PCRs, Western blots and ELISAs. BPA slightly increased HEEC tube formation and VEGF-D protein expression compared with vehicle, without affecting HEEC viability or proliferation. Bisphenol A thus caused changes in HEEC activities in vitro, and may therefore have disturbing effects on endometrial angiogenesis.

Mifepristone-exposured human endometrial endothelial cells in vitro.

The antiprogestin mifepristone has been used for more than 20 years as a medical alternative for early pregnancy termination. After mifepristone administration, significant changes have been observed in the endometrial vessels, with cell injury and cell death in capillary endothelial cells. In this study, the effect of mifepristone on human endometrial endothelial cells (HEECs) in vitro was evaluated using proliferation and viability assays, quantitative polymerase chain reaction of markers important for the regulation of angiogenesis, and by tube formation assay. There were no detectable effects of mifepristone on HEECs messenger RNA expression of the studied markers. Exposure to mifepristone did not alter tube formation. However, mifepristone exposure to HEECs cocultured with endometrial stromal cells significantly reduced the activity in the tube formation assay compared with mifepristone exposure of HEECs in monoculture. This implies that mifepristone causes changes in HEEC-associated angiogenic activity and that this effect is mediated through stromal cells via paracrine mechanisms.

Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors.

OBJECTIVE: Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women. METHODS: This is a cross-sectional study that compares postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH. RESULTS: Aromatase inhibitor-treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH. CONCLUSIONS: Women with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.

Guidelines for the design, analysis and interpretation of 'omics' data: focus on human endometrium.

BACKGROUND: 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data. METHODS: Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013. RESULTS: The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies. CONCLUSION: A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.