Infertility and Early Pregnancy Loss

The inability to achieve a recognized pregnancy may result from either failure of conception or implantation or an early postimplantation loss. Recently, a highly sensitive and specific assay for urinary human chorionic gonadotrophin (hCG) has enabled researchers to detect subclinical pregnancy losses. We used this assay to detect early pregnancy in a cohort of working women with and without fertility problems. One hundred forty eight female volunteers completed interviews, daily diaries an collected daily urine specimens for an average of seven months. The urine specimens were assayed for ovarian steroid hormones and hCG. Generalized estimating equations were used to estimate variance-corrected relative risks. There were 679 menstrual cycles at risk for pregnancy contributed by 124 of the women. Women with evidence of subfertility before or during the study period had a rate of early pregnancy loss of 70 percent compared to 21 percent of women without fertility problems (relative risk 2.63, 95%confidence interval 1.82-3.83. The risk of pregnancy loss associated with subfertility increased with age, and remained the same in women treated with clomiphene citrate. These results suggest that subfertile women have increased subclinical pregnancy losses regardless of fertility treatment, and the association between reduced fertility and advancing age may in part be related to early pregnancy loss.This study was supported by the International Business Machine Corporation

Infertility and Early Pregnancy Loss

The inability to achieve a recognized pregnancy may result from either failure of conception or implantation or an early postimplantation loss. Recently, a highly sensitive and specific assay for urinary human chorionic gonadotrophin (hCG) has enabled researchers to detect subclinical pregnancy losses. We used this assay to detect early pregnancy in a cohort of working women with and without fertility problems. One hundred forty eight female volunteers completed interviews, daily diaries an collected daily urine specimens for an average of seven months. The urine specimens were assayed for ovarian steroid hormones and hCG. Generalized estimating equations were used to estimate variance-corrected relative risks. There were 679 menstrual cycles at risk for pregnancy contributed by 124 of the women. Women with evidence of subfertility before or during the study period had a rate of early pregnancy loss of 70 percent compared to 21 percent of women without fertility problems (relative risk 2.63, 95%confidence interval 1.82-3.83. The risk of pregnancy loss associated with subfertility increased with age, and remained the same in women treated with clomiphene citrate. These results suggest that subfertile women have increased subclinical pregnancy losses regardless of fertility treatment, and the association between reduced fertility and advancing age may in part be related to early pregnancy loss.This study was supported by the International Business Machine Corporation

Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

<p>Abstract</p> <p>Background</p> <p>Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles.</p> <p>Methods</p> <p>The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3–5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel.</p> <p>Results</p> <p>A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3–5 days after retrieval. During the peri-implantation period (3–5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group.</p> <p>Conclusion</p> <p>Luteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P + E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes.</p

Cigarette Smoking, Androgen Levels, and Hot Flushes in Midlife Women

Connection of the Forum canopy roof to one of the ring of buildings, and open passage out to the street; A Sony-sponsored building complex located at the Potsdamer Platz, which after the fall of the Berlin Wall (1989) presented a largely empty 60 hectares site; an attractive central location for development. Multiple mixed-use buildings share a central area covered by an enormous circular canopy structure, the "Forum". The complex includes the Forum, and a 103 metre tall, glass office tower; it also integrates the historic Emperor’s Hall (Kaisersaal) and parts of the former Hotel Esplanade. In 1996 the Emperor's Hall was translocated by the means of air cushions by 75 meters to today's location. Construction of the roof began in fall of 1998 and the completion lasted more than two years. At its highest point, the roof measures up to 67 meters above the Forum and has a free span of 102 meters length on the main axis and 77 meters length on the ancillary axis. The average translucence is at 50%. The textile sails consist of self-cleaning, teflon-coated fabric. More than 5,250 square meters are spanned. About 520 tons of steel were used for the ring beam and 100 tons for the king post. The impressive roof consists of 105 tons of safety glass, which is 16 mm thick and spans over 3,500 square meters. Source: Sony Center am Potsdamer Platz [website]; http://www.sonycenter.de/en/ (accessed 7/12/2013

Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

Background: Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles. Methods: The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3-5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel. Results: A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p &lt; 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3-5 days after retrieval. During the peri-implantation period (3-5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group. Conclusion: Luteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P + E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes

Risk Factors for Extended Duration and Timing of Peak Severity of Hot Flashes.

OBJECTIVE:To identify risk factors associated with the duration of hot flashes and the time of peak hot flash severity in mid-life women. METHODS:A cohort of 647 women reporting hot flashes were followed for 1-7 years, with survey data and hormone measurements. Survival analysis determined the association of risk factors with the duration of hot flashes. Linear regression determined the association of risk factors with the time of peak severity. Final models were determined through stepwise model selection. RESULTS:Average hot flash duration was 2.5 years (range: 1-33), with peak severity on average at 2.96 years (range: 1-20). Duration of hot flashes was associated with race, education, menopause status, smoking history, BMI, alcohol consumption, leisure activity levels, and levels of estradiol and progesterone. In the final model, only race, alcohol consumption, leisure activity, and menopause were retained. White women had significantly shorter hot flash durations than non-white women. Women consuming at least 12 alcoholic drinks in the previous year had a significantly shorter duration of hot flashes with a smaller effect of hot flash duration on increasing in time to peak severity compared to those who consumed less than 12 alcoholic drinks in that year. Higher serum progesterone levels were associated with later peak severity if the duration of the hot flashes was less than 2 years and an earlier peak severity otherwise. CONCLUSIONS:These results suggest that some behaviors (such as moderate alcohol consumption) are associated with shorter durations of hot flashes, and that progesterone was associated with the dynamics of hot flash severity

The Midlife Women’s Health Study – a study protocol of a longitudinal prospective study on predictors of menopausal hot flashes

Abstract Background The Midlife Women’s Health Study (MWHS) was developed to address some of the gaps in knowledge regarding risk factors for hot flashes among generally healthy midlife women during their menopausal transition. This manuscript describes the methods from the study and the main findings that were published to date, with a focus on predictors of hot flashes. This study was initially funded to test the hypothesis that obesity is associated with an increased risk of hot flashes through mechanisms that involve ovarian failure, altered sex steroid hormone levels, and selected genetic polymorphisms. Methods/Design The MWHS was conducted between 2006 and 2015 as a prospective longitudinal population-based study of generally healthy midlife women (ages 45 to 54 years) during their natural menopausal transition. Women were eligible if they had intact uteri and both ovaries and reported having at least 3 menstrual periods in the last 12 months. Exclusion criteria included pregnancy, cancer, and use of hormonal/hormone-like supplements. Overall, 780 women were recruited into the study. The majority of study participants were followed for 4 to 7 years. At annual visits, women donated blood and urine samples, completed questionnaires, had a vaginal ultrasound, and had their anthropometric measurements taken. Discussion Several risk factors for menopausal hot flashes were identified or confirmed, including older age, perimenopausal status, current and former cigarette smoking, lower estradiol levels, lower progesterone levels, black race, and depressive symptoms. Factors that were associated with decreased odds of hot flashes included moderate alcohol consumption and more than 5 years of cessation of cigarette smoking. Body mass index was not associated with hot flashes. The MWHS has provided important information regarding hot flashes. The study methods are rigorous and can be easily adopted by research groups investigating naturally occurring menopausal hot flashes