Andy Huang

Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria

OBJECTIVE To determine the prevalence of elevated total and free T, and DHEAS, alone and in combination, in patients with polycystic ovary syndrome (PCOS). DESIGN Cross-sectional analysis. SETTING Tertiary care academic medical center. PATIENT(S) Seven hundred twenty patients diagnosed with PCOS according to the National Institutes of Health 1990 criteria. INTERVENTION(S) History, physical examination, and blood sampling. MAIN OUTCOME MEASURE(S) Hyperandrogenemia, defined as at least one androgen value above the 95th percentile of 98 healthy control women (i.e., total T >88 ng/dL, free T >0.75 ng/dL, and DHEAS >2,750 ng/mL). RESULT(S) A total of 716 subjects with PCOS were included. The overall prevalence of hyperandrogenemia in PCOS was 75.3%. Supranormal levels of free T were present in 57.6%, of total T in 33.0%, and of DHEAS in 32.7% of patients with PCOS. When assessing the prevalence of two abnormal values, the prevalence of simultaneously elevated androgens was lowest with total T and DHEAS (1.7%) and highest with total T and free T (20.4%). Altogether, simultaneous elevations in all three markers were found in 8.7% of subjects with PCOS. CONCLUSION(S) Approximately three-fourths of patients with PCOS diagnosed by the National Institutes of Health 1990 criteria have evidence of hyperandrogenemia; the single most predictive assay was the measurement of free T with approximately 60% of patients demonstrating supranormal levels.

The first trimester human placenta is a site for terminal maturation of primitive erythroid cells

Embryonic hematopoiesis starts via the generation of primitive red blood cells (RBCs) that satisfy the embryos immediate oxygen needs. Although primitive RBCs were thought to retain their nuclei, recent studies have shown that primitive RBCs in mice enucleate in the fetal liver. It has been unknown whether human primitive RBCs enucleate, and what hematopoietic site might support this process. Our data indicate that the terminal maturation and enucleation of human primitive RBCs occurs in first trimester placental villi. Extravascular ζ-globin(+) primitive erythroid cells were found in placental villi between 5-7 weeks of development, at which time the frequency of enucleated RBCs was higher in the villous stroma than in circulation. RBC enucleation was further evidenced by the presence of primitive reticulocytes and pyrenocytes (ejected RBC nuclei) in the placenta. Extravascular RBCs were found to associate with placental macrophages, which contained ingested nuclei. Clonogenic macrophage progenitors of fetal origin were present in the chorionic plate of the placenta before the onset of fetoplacental circulation, after which macrophages had migrated to the villi. These findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis.

Degree of hyperinsulinemia, independent of androgen levels, is an important determinant of the severity of hirsutism in PCOS.

OBJECTIVE To determine whether the severity in hyperandrogenemia determines, to a significant degree, the severity of hirsutism in patients with polycystic ovary syndrome (PCOS). DESIGN Cross-sectional study. SETTING Tertiary care academic referral center. PATIENT(S) A total of 749 patients with PCOS. INTERVENTION(S) History and physical examination, blood sampling. MAIN OUTCOME MEASURE(S) Hirsutism defined by a value of >or=6 using the modified Ferriman-Gallwey (mFG) score, age, body mass index (BMI), calculated homeostatic assessment for insulin resistance (HOMA-IR) value, and levels of total (TT) and free (FT) testosterone, dehydroepiandrosterone sulfate (DHEAS) 17-hydroxyprogesterone (17OH-P), and fasting insulin (INS) and glucose (GLC). RESULT(S) Univariate correlations revealed associations between the mFG score and INS, 17OH-P, HOMA-IR, and BMI. Multivariate classification and regression tree analysis indicated that INS had the most significant association with mFG score and that at higher INS levels T played an additional role whereas at lower INS levels 17OH-P had an effect; however, this model accounted for only 8.2% of total variation in mFG score. CONCLUSION(S) Insulin appears to have a direct effect on the severity of hirsutism in PCOS and appears to have a synergistic interaction with TT. Notably, over 90% of the variation in the mFG score was not related to the factors studied and likely reflects intrinsic factors related to pilosebaceous unit function or sensitivity and to other factors not yet assessed.

Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome

OBJECTIVE To test the hypothesis that increasing DHEAS levels is associated with improved insulin resistance in patients with polycystic ovary syndrome (PCOS). DESIGN Cross-sectional cohort analysis. SETTING Academic medical center. PATIENT(S) Three hundred fifty-two women with PCOS. INTERVENTION(S) Patients presenting for evaluation of symptoms related to androgen excess were evaluated physically and biochemically through laboratory analysis. MAIN OUTCOME MEASURE(S) Circulating DHEAS, total T, free T, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) levels, and calculated homeostasis model assessment of insulin resistance (HOMA-IR). RESULT(S) Bivariate analysis indicated that all parameters were associated with HOMA-IR, except 17-OHP and age, and confirmed a negative correlation between DHEAS and HOMA-IR. Multivariate analysis indicated that increases in DHEAS, SHBG, 17-OHP, and age were associated with decreasing HOMA-IR, whereas increases in free T, body mass index (BMI), and waist-to-hip ratio (WHR) were associated with increasing HOMA-IR. In decreasing order of importance, the following variables predicted insulin resistance: BMI > WHR > age > DHEAS > free T > SHBG > 17-OHP. CONCLUSION(S) DHEAS is negatively correlated to insulin resistance in patients with PCOS, and in our model ranked just behind other well-established predictors including BMI, WHR, and age. Whether this is due to a direct beneficial effect on insulin action by adrenal androgens such as DHEA, or whether DHEAS simply reflects the circulating levels of hyperinsulinemia, remains to be determined.

Prevalence of chromosomal mosaicism in pregnancies from couples with infertility

OBJECTIVE To determine if mosaicism that occurs in infertility and assisted reproductive technologies continues in the late first trimester and if this is unique to infertility or occurs in all pregnancies. DESIGN Retrospective case-controlled study. SETTING University hospital. PATIENT(S) 5337 consecutive chorionic villus samplings (CVS). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Mosaic karyotypes at CVS. RESULT(S) We confirmed 69 mosaic karyotypes, a rate of 1.29%. Comparing spontaneous pregnancies with pregnancies from infertility treatment, no difference was found in the prevalence of mosaicism: 1.22% versus 1.32%, respectively. Subgroup analysis of infertile couples, comparing in vitro (assisted reproduction) with in vivo fertilization (other treatments) revealed a mosaicism rate of 1.84% and 0.41%, respectively. Confined placental mosaic (CPM) rates for infertility treated pregnancies and spontaneously conceived pregnancies were 0.88% and 0.92%, respectively. Subgroup analysis of infertile patients revealed a CPM rate of 1.15% for in vitro fertilization treatment and 0.41% for in vivo fertilization treatment. These results were not statistically significant. CONCLUSION(S) There was no difference in the prevalence of mosaicism at the end of the first trimester in pregnancies conceived spontaneously compared with those with infertility. There was no difference in the prevalence of mosaicism when in vitro and in vivo treatment were compared.

Expansion on Stromal Cells Preserves the Undifferentiated State of Human Hematopoietic Stem Cells Despite Compromised Reconstitution Ability

Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38−CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38−CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-6 in in vitro fertilization cycles

OBJECTIVE To assess whether gonadotropin-induced changes in E(2) alter serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and proinflammatory cytokines. DESIGN Prospective collection of serum in patients undergoing IVF. SETTING University hospital. PATIENT(S) Twenty-four infertile women. INTERVENTION(S) Serum collection at baseline, in the mid and late follicular phases, at oocyte retrieval, and in the mid and late luteal phases. MAIN OUTCOME MEASURE(S) Samples were assayed for sVCAM-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and E(2). RESULT(S) The VCAM-1 was maximally suppressed in the luteal phase. Luteal sVCAM-1 levels correlated [1] positively with the patients age, units of gonadotropins, day 3 FSH levels and [2] negatively with [a] the follicular, retrieval, and luteal E(2) levels and [b] the number of preovulatory follicles and oocytes retrieved. Similar correlations were noted in the late luteal phase. Serum TNF-alpha reached a peak in the mid-follicular phase and a nadir in the luteal phase. The TNF-alpha levels at retrieval correlated [1] positively with the patients age and [2] negatively with E(2) and number of preovulatory follicles and retrieved oocytes. The IL-6 levels were suppressed in the follicular phase and correlated negatively with E(2) levels. CONCLUSION(S) Changes in E(2) levels seen during gonadotropin stimulation significantly alter VCAM-1 expression and induce changes in serum IL-6 and TNF-alpha levels.

How Obamacare will impact reproductive health.

For many years, health care delivery in the United States was accomplished through a complicated and evolving series of publicly and privately available insurance programs. In recent years, the increasing cost of health care as well as the relatively large number of individuals without any health care insurance coverage has prompted repeated attempts to modify or overhaul the current health care delivery paradigm. The largest legislative change to this system occurred on March 23, 2010, when President Barack Obama signed into law the Patient Protection and Affordable Care Act (PPACA).The PPACA is a multifaceted and sweeping piece of legislation. The law introduces a myriad number of changes into both public and private health insurance. Understanding the law, its implications, and how to navigate through these changes is essential to provide high-quality health care to patients. Although the law or parts of it are still at risk of being modified either through judicial or political action, it is important to recognize the current aspects of the law to understand any future modifications. Providing health care coverage in the United States is sure to be as it has always been: a constantly changing and evolving set of private and public policies that carry with them significant complexities and challenges. Health care providers must constantly strive to maximize access to and quality of medical care in whatever paradigm evolves in the future.