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

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.Peer reviewe

Transcriptome Profiling of Human Pre-Implantation Development

BACKGROUND: Preimplantation development is a crucial step in early human development. However, the molecular basis of human preimplantation development is not well known. METHODOLOGY: By applying microarray on 397 human oocytes and embryos at six developmental stages, we studied the transcription dynamics during human preimplantation development. PRINCIPAL FINDINGS: We found that the preimplantation development consisted of two main transitions: from metaphase-II oocyte to 4-cell embryo where mainly the maternal genes were expressed, and from 8-cell embryo to blastocyst with down-regulation of the maternal genes and up-regulation of embryonic genes. Human preimplantation development proved relatively autonomous. Genes predominantly expressed in oocytes and embryos are well conserved during evolution. SIGNIFICANCE: Our database and findings provide fundamental resources for understandin

Characteristics and possible function of pinopodes seen on the surface of the receptive human endometrium

A synchronized development of embryo and endometrium is a prerequisite for a successful implantation. During the time of implantation, pinopodes appear on the endometrial surface. The precise function of these structural markers of endometrial receptivity is not known, but it is generally believed that they play a role in the implantation process. Further understanding of the function of these biomarkers and their role in embryo implantation could aid in better diagnosis and treatment of infertile couples in the future

Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility

Background: Infertile women might get pregnant sometime after fertility treatment, but today, there is no prediction model on who will eventually have children. The objective of the present study was to characterize hormone levels in an arbitrary menstrual cycle in women with unexplained infertility and male infertility, and to determine the predictive value for long-term possibility of live birth. Methods: In this cross-sectional study, with 71 infertile women with diagnosis unexplained infertility and male infertility, blood samples were obtained during the proliferative and secretory phases of an arbitrary menstrual cycle. Serum concentrations of FSH, LH, AMH, inhibin B, estradiol, progesterone, PRL and TSH were determined. The predictive value of ovulation and hormonal analysis was determined by identifying the proportion of women with at least one live birth. Mann Whitney U test, chi2 test and Spearman's correlation were used for statistical analysis. A value of p < 0.05 was considered statistically significant. Results: There were no differences in hormone values and live birth rates between women with unexplained infertility and male infertility. The best sole predictors of live birth were age of the women, followed by ovulatory cycle, defined as serum progesterone concentration of greater than or equal to 32 nmol/L, and a serum TSH concentration of less than or equal to 2.5 mIU/L. Combining the age with the ovulatory cycle and serum TSH less than or equal to 2.5 mIU/L or serum AMH greater than or equal to 10 pmol/L the predictive value was close to 90%. Conclusions: Age in combination with the presence of an ovulatory cycle and serum TSH or serum AMH is predictive for long-term live birth. The advantage of serum AMH compared with serum TSH is the very little variation throughout the menstrual cycle, which makes it a useful tool in infertility diagnosis

Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial

STUDY QUESTION Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate? SUMMARY ANSWER Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births. WHAT IS KNOWN ALREADY Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited. STUDY DESIGN, SIZE, DURATION This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration. LIMITATIONS, REASONS FOR CAUTION The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos. WIDER IMPLICATIONS OF THE FINDINGS Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmo, Sweden. The authors have no personal conflicting interests to declare. DATE OF FIRST PATIENT'S ENROLMENT 18 February 2013

HRG C688T 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

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

Ultrasonographic findings in spontaneous miscarriage: relation to euploidy and aneuploidy

Objective: To evaluate a possible correlation between transvaginal ultrasound findings in miscarriages and cytogenetic analyses from chorionic villi obtained by dilatation and curettage. Design: Prospective, population-based study. Setting: University-based hospital. Patient(s): Five hundred seventy-six women with spontaneous miscarriage diagnosed between 6 and 12 completed pregnancy weeks. Intervention(s): Transvaginal ultrasonography and dilatation and curettage. Main Outcome Measure(s): Cytogenetic analyses and ultrasound measurement of embryonic pole. Result(s): The mean gestational age was 9.5 weeks. Chromosomal analyses were successful in 259 cases, 159 with cytogenetic abnormalities and 100 euploidy. Empty gestational sacs were equally often found in euploidy and aneuploidy, whereas small embryonic or fetal poles were significantly more often associated with aneuploidy. Conclusion(s): A smaller than expected fetal size when a miscarriage is diagnosed during the first trimester is significantly associated with a chromosomal aberration. (Fertil Steril(R) 2011;95:221-4. (C) 2011 by American Society for Reproductive Medicine.