Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR)

<p>Abstract</p> <p>Background</p> <p>With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review.</p> <p>Methods</p> <p>PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [<dehydroepiandrosterone or DHEA or androgens or testosterone > and <ovarian reserve or diminished ovarian reserve or ovarian function >]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed.</p> <p>Results</p> <p>Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia.</p> <p>Discussion</p> <p>Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow.</p

Defining ovarian reserve to better understand ovarian aging

Though a widely utilized term and clinical concept, ovarian reserve (OR) has been only inadequately defined. Based on Medline and PubMed searches we here define OR in its various components, review genetic control of OR, with special emphasis on the FMR1 gene, and discuss whether diminished OR (DOR) is treatable. What is generally referred to as OR reflects only a small portion of total OR (TOR), a pool of growing (recruited) follicles (GFs) at different stages of maturation. Functional OR (FOR) depends on size of the follicle pool at menarche and the follicle recruitment rate. Both vary between individuals and, at least partially, are under genetic control. The FMR1 gene plays a role in defining FOR at all ages. Infertility treatments have in the past almost exclusively only centered on the last two weeks of folliculogenesis, the gonadotropin-sensitive phase. Expansions of treatments into earlier stages of maturation will offer opportunity to significantly improve ovarian stimulation protocols, especially in women with DOR. Dehydroepiandrosterone (DHEA) may represent a first such intervention. Data generated in DHEA-supplemented women, indeed, suggest a new ovarian aging concept, based on aging of ovarian environments and not, as currently is believed, aging oocytes

Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)

<p>Abstract</p> <p>Background</p> <p>Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy.</p> <p>Methods</p> <p>In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos.</p> <p>Results</p> <p>DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031).</p> <p>Discussion</p> <p>Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.</p

The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment?

<p>Abstract</p> <p>Background</p> <p>Effects of androgens on follicle maturation have been controversial for some time. Here, we review the potential of their applications in improving human ovulation induction, based on human and animal data, reported in the literature.</p> <p>Methods</p> <p>We reviewed the published literature for the years 2005-2011, using relevant key words, in PubMed, Medline and Cochrane reviews, and then performed secondary reviews of referenced articles, which previously had not been known or preceded the searched time period. A total of 217 publications were reviewed.</p> <p>Results</p> <p>Contrary to widely held opinion, recent data, mostly developed in the mouse, convincingly demonstrate essential contribution of androgens to normal follicle maturation and, therefore, female fertility. Androgens appear most engaged at preantral and antral stages, primarily affect granulosa cells, and exert effects via androgen receptors (AR) through transcriptional regulation but also in non-genomic ways, with ligand-activated AR modulating follicle stimulating hormone (FSH) activity in granulosa cells. While some androgens, like testosterone (T) and dehydroepiandrosterone (DHEA), appear effective in improving functional ovarian reserve (FOR) in women with diminished ovarian reserve (DOR), others may even exert opposite effects. Such differences in androgens may, at least partially, reflect different levels of agonism to AR.</p> <p>Discussion</p> <p>Selective androgens appear capable of improving early stages of folliculogenesis. They, therefore, may represent forerunners of a completely new class of ovulation-inducing medications, which, in contrast to gonadotropins, affect follicle maturation at much earlier stages.</p

Discordances between follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility

<p>Abstract</p> <p>Background</p> <p>Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients.</p> <p>Methods</p> <p>We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR.</p> <p>Results</p> <p>Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages.</p> <p>Discussion</p> <p>Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF.</p

Crack Detection in Cantilever Beam by Frequency based Method

AbstractDuring the last few decades, intense research on the detection of crack using the vibration based techniques has been done and various approaches have been developed by researchers. In the present paper, detection of the crack presence on the surface of beam-type structural element using natural frequency is presented. First two natural frequencies of the cracked beam have been obtained experimentally and used for detection of crack location and size. Detected crack locations and size are compared with the actual results and found to be in good agreement. Also, the effect of the crack location and the crack depth on the natural frequency is presented

Association of FMR1 Genotypes with In Vitro Fertilization (IVF) Outcomes Based on Ethnicity/Race

The FMR1 gene, mapping to an area of the X chromosome closely associated with autoimmunity also affects ovarian reserve, with specific genotypes associated with distinct ovarian aging patterns. They, therefore, could also be associated with differences of in vitro fertilization (IVF) outcomes, reported between races/ethnicities. We analyzed 339 consecutive IVF patients, 232 Caucasian, 59 African and 48 Asian, for FMR1 genotypes, and tested by multiple logistic regressions for associations between race/ethnicity, FMR1 genotype, autoimmunity and pregnancy chances with IVF. FMR1 genotypes were predictive of pregnancy (P = 0.046), het-norm/low most significantly and with decreasing chance in comparison to norm genotypes (OR 0.44; 95% CI 0.23–0.85; P = 0.014). Race/ethnicity was, overall, independently associated (P = 0.03), African demonstrating decreased odds in comparison to Caucasian (OR 0.33. 95%CI 0.13–0.79; P = 0.014). Autoimmunity did not differ but interaction of autoimmunity with FMR1 genotype almost reached significance (P = 0.07). Logistic regression with race/ethnicity and interaction between FMR1 genotype and autoimmunity in the model, demonstrated 2.5-times the odds of being associated with autoimmune positivity (OR 2.5, 1.34–4.55; P = 0.004). FMR1 genotypes offer a possible explanation for differences in IVF outcomes between races/ethnicities

Classroom assessment and education: challenging the assumptions of socialisation and instrumentality

The opportunity offered by the Umea Symposium to probe the intersection of quality and assessment immediately brings into focus a wider issue – that of the quality of education which assessment aspires to support. Prompted by recent research into formative assessment in Scottish primary school contexts, the paper explores how formative assessment has become associated with an overly benign understanding of learning which misrecognises the possibility of undesirable learning and does not seem to address the inherently political nature of education. Having illuminated the potential inequities of formative assessment practices, the paper then asks what role formative assessment might play to support an understanding of education that is not simply about the transmission of traditional social norms, but also aspires to illuminate their social construction and their political nature

The Impact in Older Women of Ovarian FMR1 Genotypes and Sub-Genotypes on Ovarian Reserve

We recently associated ovarian FMR1genotypes and sub-genotypes with distinct ovarian aging patterns. How they impact older females is, however, unknown. We, therefore, investigated 217 consecutive first in vitro fertilization (IVF) cycles in women >40 assessing oocyte yields, stratified for better (anti-Müllerian hormone, AMH >1.05 ng/mL) or poorer (AMH≤1.05 ng/mL) functional reserve (FOR)). Mean age was 42.4±2.0 years, mean AMH 0.76±0.92 ng/mL and mean oocyte yield 5.3±5.4. Overall, and in women with better FOR, FMR1 did not affect oocyte yields. With poorer FOR (AMH≤1.05 ng/mL) women with het-norm/high, however, demonstrated higher oocyte yields (5.0±3.8) than those with het-norm/low sub-genotype 3.1±2.5; P = 0.03), confirmed after log conversion. Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions

The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization

<p>Abstract</p> <p>Background</p> <p>Impact of fetal gender on prematurity has been primarily investigated in singleton pregnancies. In an attempt to understand better how fetal gender may affect gestational length in twin gestations after in vitro fertilization, same-sex twins and opposite twins were compared for pregnancy duration.</p> <p>Methods</p> <p>This study evaluated 113 women at ages 20 to 39 years with consecutive dichorionic-diamniotic twin gestations after assisted reproduction. All pregnancies were results of fresh in vitro fertilization (IVF) cycles with use of autologous oocytes and sperm and were delivered at up to 37 weeks of gestation at a University-based high-risk, maternal-fetal medicine unit.</p> <p>Results</p> <p>Both groups did not differ in baseline characteristics, such as maternal ages, indications for fertility treatments, number of previous IVF attempts, body mass index and parity. Opposite sex- twins, however, presented with significantly shorter gestational age at birth (32.9 +/- 3.4 weeks) than same-sex twins (34.3 +/- 2.5 weeks), (p < 0.05). Younger maternal age was also associated with shorter pregnancy duration (p < 0.05).</p> <p>Conclusions</p> <p>Fetal gender mix serves as risk factor for more significant prematurity in dichorionic-diamniotic twins after assisted reproduction with opposite sex twins at higher risk than same sex-twins.</p