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1.  The Correlation Between Self-Reported and Measured Height, Weight, and BMI in Reproductive Age Women 
Maturitas  2013;76(2):10.1016/j.maturitas.2013.07.010.
This prospective, cross-sectional study of 60 women compares self- reported height, weight, and BMI with measured values. Self-reported BMI (29.0 ± 8.37kg/m2) was slightly lower than measured BMI (29.1 ± 8.38kg/m2) (p=0.4). Eighty percent of participants reported a BMI in the same category in which their BMI was measured. Pearson's correlation coefficient for height (0.96, p<0.001), weight (0.99, p<0.001), and BMI (0.99, p<0.001) were high. Reproductive age women accurately reported their height and weight.
doi:10.1016/j.maturitas.2013.07.010
PMCID: PMC3816555  PMID: 23958434
self-reported weight; self-reported height; reproductive age women
2.  Association of Ethnicity with Involuntary Childlessness and Perceived Reasons for Infertility: Baseline Data from the Study of Women’s Health Across the Nation (SWAN) 
Fertility and Sterility  2011;96(5):1200-5.e1.
Objective
To evaluate whether ethnicity is associated with involuntary childlessness and perceived reasons for difficulties in becoming pregnant .
Design
Cross-sectional analysis of baseline data from a longitudinal cohort
Setting
Multiethnic, community-based observational study of US women
Patient(s)
3149 midlife women, aged 42-52
Main Outcome Measure(s)
Involuntary childlessness and perceived etiology of infertility
Result(s)
One hundred and thirty-three subjects (4.2%) were involuntarily childless, defined by a reported history of infertility and nulliparity. Ethnicity was significantly associated with self-reported involuntary childlessness. After controlling for economic and other risk factors, African-American (OR 0.30; 95% CI 0.15 – 0.59) and Chinese women (OR 0.36; 95% CI 0.14 – 0.90) were less likely to suffer from involuntary childlessness as compared to non-Hispanic Caucasian women.
Additionally, 302 subjects reported a perceived etiology of infertility. An unexpectedly large proportion of these women (24.5%, 74 out of 302) reported etiologies not known to cause infertility (i.e. tipped uterus, ligaments for tubes were stretched), with African-American women having been most likely to report these etiologies (OR 2.81; 95% CI 1.26 – 6.28) as the reason for not becoming pregnant.
Conclusion(s)
Ethnicity is significantly associated with involuntary childlessness and perceived etiology of infertility. Misattribution of causes of infertility is common and merits further consideration with respect to language or cultural barriers as well as possible physician misattribution.
doi:10.1016/j.fertnstert.2011.08.039
PMCID: PMC3278161  PMID: 21958690
childlessness; infertility; ethnicity
3.  QUANTIFICATION OF NUCLEOLAR CHANNEL SYSTEMS: UNIFORM PRESENCE THROUGHOUT THE UPPER ENDOMETRIAL CAVITY 
Fertility and sterility  2012;99(2):558-564.
Objective
To determine the prevalence of nucleolar channel systems (NCSs) by uterine region applying continuous quantification.
Design
Prospective clinical study.
Setting
Tertiary care academic medical center.
Patients
42 naturally cycling women who underwent hysterectomy for benign indications.
Intervention
NCS presence was quantified by a novel method in six uterine regions, fundus, left cornu, right cornu, anterior body, posterior body, and lower uterine segment (LUS), using indirect immunofluorescence.
Main Outcome Measures
Percent of endometrial epithelial cells (EECs) with NCSs per uterine region.
Results
NCS quantification was observer-independent (intraclass correlation coefficient [ICC] = 0.96) and its intra-sample variability low (coefficient of variability [CV] = 0.06). 11/42 hysterectomy specimens were midluteal, 10 of which were analyzable with 9 containing over 5% EECs with NCSs in at least one region. The percent of EECs with NCSs varied significantly between the lower uterine segment (6.1%; IQR = 3.0-9.9) and the upper five regions (16.9%; IQR = 12.7-23.4) with fewer NCSs in the basal layer of the endometrium (17% +/−6%) versus the middle (46% +/−9%) and luminal layers (38% +/−9%) of all six regions).
Conclusions
NCS quantification during the midluteal phase demonstrates uniform presence throughout the endometrial cavity, excluding the LUS, with a preference for the functional, luminal layers. Our quantitative NCS evaluation provides a benchmark for future studies and further supports NCS presence as a potential marker for the window of implantation.
doi:10.1016/j.fertnstert.2012.10.027
PMCID: PMC4074880  PMID: 23137760
nucleolar channel system (NCS); endometrium; receptivity; secretory transformation
4.  Aromatase Inhibition Causes Increased Amplitude, but not Frequency, of Hypothalamic-Pituitary Output in Normal Women 
Fertility and sterility  2011;95(6):2063-2066.
Objective
To better understand the site and mode of action of aromatase inhibitors.
Setting
Academic research environment.
Patients and Design
5 eumenorrheic (non-PCOS), early follicular phase women of normal BMI (mean = 20.47 +/− 0.68 kg/m2) and 12 normal weight, mid-reproductive aged, early follicular phase, normal BMI (mean = 20.8 +/− 1.7 kg/m2) historical controls.
Interventions
2.5mg letrozole daily for 7 days. Women were sampled with daily, first morning voided urine collections, thrice weekly blood sampling, and 4 hours of q 10 minute frequent blood sampling
Main outcome measures
Serum LH measured using a well-characterized immunofluorometric assay. LH pulse characteristics were compared between treated and control groups using t tests.
Results
Mean LH and LH pulse amplitude more than doubled in women who had taken letrozole compared to controls, but the LH pulse frequency did not differ between women taking letrozole and controls.
Conclusions
These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that mean LH and LH pulse amplitude, but not frequency, increased after letrozole suggests a possible pituitary site of action.
doi:10.1016/j.fertnstert.2011.01.158
PMCID: PMC3080458  PMID: 21353673
Hypothalamic-Pituitary-Gonadal Axis; Luteinizing Hormone; Aromatase Inhibitor; Letrozole; Pituitary; Ovary
5.  Nutrition And Reproduction: Is There Evidence To Support A “Fertility Diet” To Improve Mitochondrial Function? 
Maturitas  2013;74(4):309-312.
Normal function of mitochondria plays an essential role in enabling reproductive capacity. To date, few studies have investigated the role of promoting mitochondrial health in relation to fertility in humans. Selected nutritional interventions have demonstrated a potential to enhance mitochondrial function, suggesting a promise for future research for fertility treatment. This review summarizes the extant literature and highlights a putative role of particular nutrients in promotion of mitochondrial function, including in vitro, animal and human studies. Strong basis exists to advocate for further investigation of nutritional treatments for infertility patients.
doi:10.1016/j.maturitas.2013.01.011
PMCID: PMC4019337  PMID: 23376023
nutrition; fertility; mitochondria; obesity; supplement
6.  Association of adolescent obesity and lifetime nulliparity – SWAN, the study of women's health across the nation 
Fertility and sterility  2009;93(6):2004-2011.
Objective
To evaluate whether adolescent obesity is associated with difficulties for becoming pregnant later in life.
Design
Cross-sectional analysis of baseline data from a longitudinal cohort
Setting
Multiethnic, community-based observational study of US women
Patient(s)
3154 midlife women
Main Outcome Measure(s)
Lifetime nulliparity and lifetime nulligravidity
Result(s)
527 women (16.7%) women had never delivered a baby. Participants were categorized by self-reported high school body mass index (BMI): underweight (< 18.5 kg/m2), normal (18.5 to 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (> 30 kg/m2). The prevalence of lifetime nulliparity increased progressively across the high school BMI categories: 12.7%, 16.7%, 19.2%, and 30.9%, respectively (p<0.001). Multivariable logistic regression analysis confirmed that women who were obese adolescents had significantly higher odds of remaining childless as compared to normal weight women (odds ratio [OR] 2.84, 95% confidence intervals [CI] 1.59 to 5.10) after adjusting for adult BMI, history of non-gestational amenorrhea, marital status, ethnicity, study site, and measures of socioeconomic status. Furthermore, adolescent obesity was associated with lifetime nulligravidity (OR 3.93, 95% CI 2.12 to 7.26).
Conclusion(s)
Adolescent obesity is associated with lifetime nulliparity and nulligravidity in midlife U.S. women.
doi:10.1016/j.fertnstert.2008.12.059
PMCID: PMC2891509  PMID: 19185860
adolescents; body mass index; gravidity; obesity; parity
7.  Serum progesterone on the day of hCG administration predicts clinical pregnancy of sibling frozen embryos 
Fertility and sterility  2008;92(6):1880.
Objective
To evaluate patient characteristics and fresh IVF cycle parameters that influence success of sibling frozen-thawed embryo transfer (FET) cycles.
Design
Retrospective study.
Setting
Academic infertility practice.
Patient(s)
Infertile women undergoing FET cycles utilizing embryos cryopreserved on day 3 post-insemination following an initial fresh IVF cycle.
Intervention(s)
90 FET cycles.
Main Outcome Measure(s)
Clinical pregnancy (CP).
Result(s)
The likelihood of CP following FET was significantly higher in women who had achieved CP in the preceding fresh IVF cycle (71.4% vs. 40.6%). Multivariable logistic regression analysis confirmed that patients achieving CP following the fresh IVF cycle were more likely to achieve CP following FET (OR= 5.5, 95% CI 1.2 to 25.3) after adjusting for age, number and cleavage status of embryos transferred. Additionally, higher serum levels of progesterone on the day of hCG administration emerged as predictive of CP after FET at a statistically significant level.
Conclusion(s)
The outcome of the fresh ET cycle is the foremost predictor of CP after FET of the sibling embryos. Relationship between serum P on the day of hCG administration in the fresh cycle and the outcome of subsequent FET is noteworthy and merits further investigation.
doi:10.1016/j.fertnstert.2008.09.017
PMCID: PMC2814243  PMID: 18851847
Frozen-thawed embryos; progesterone; in vitro fertilization
8.  Recruitment Challenges of a Multicenter Randomized Controlled Varicocelectomy Trial 
Fertility and sterility  2011;96(6):1299-1305.
Study Objective
To review reasons for suboptimal recruitment for a randomized controlled trial (RCT) of varicocelectomy vs. intrauterine insemination for treatment of male infertility, and suggest means to improve future study recruitment.
Design
A survey of RMN participating sites.
Setting
The Reproductive Medicine Network.
Patients
N/A
Interventions
N/A
Main Outcome Measures
Ascertain reasons for inadequate recruitment and suggest improvements for future varicocelectomy trails.
Results
This study screened 7 and enrolled 3 couples with the first couple randomized on 6/30/2010. The study was subsequently stopped on 03/30/2011. The following themes were cited most frequently by sites and therefore determined to be most likely to have played a role in suboptimal recruitment: (1) men must be screened at the beginning of a couple's infertility evaluation, (2) inclusion of infertile women who have failed previous fertility interventions appeared to be associated with couple intolerance of a placebo arm, and (3) there appeared to be bias against the use of unstimulated IUI cycles, indicating a prejudicial preference for surgical intervention in the male partner.
Conclusions
Improved recruitment may be realized through screening infertile men as early as possible while minimizing study-related time commitments. Focused patient education may promote improved ‘equipoise’ and acceptance of a placebo arm in male infertility studies. Lastly, creative approaches to implementing varicocelectomy trials must be considered in addition to having a network of motivated researchers who carry a high volume of possible study participants, as screening of very large numbers may be needed to complete clinical trial enrollment. Clinicaltrials.gov: NCT00767338.
doi:10.1016/j.fertnstert.2011.10.025
PMCID: PMC3243664  PMID: 22130101
Recruitment; consent; randomization; accrual; enrollment; prospective; varicocele; varicocelectomy
9.  The nucleolar channel system reliably marks the midluteal endometrium regardless of fertility status: a fresh look at an old organelle 
Fertility and Sterility  2010;95(4):1385-9.e1.
Objective
To determine if nucleolar channel systems (NCSs) in the midluteal endometrium are associated with overall fertility status and/or with unexplained infertility.
Design
Retrospective and prospective clinical studies.
Setting
Repository of stored specimens from prior multicenter study and private infertility center, respectively.
Patients
Retrospective study: 97 women (49 fertile couples, 48 infertile couples) who had been randomized for endometrial biopsy during the midluteal or late luteal phase. Prospective study: 78 women with a variety of infertility diagnoses.
Intervention
Endometrial biopsies were obtained and assessed for the presence of NCSs by indirect immunofluorescence.
Main Outcome Measures
NCS presence was graded semi-quantitatively and dichotomized as normal versus low or absent.
Results
Normal NCS presence was significantly associated with the midluteal phase compared to the late luteal phase (80% versus 29%). However, there was no association between NCS presence and fertility status or between NCS presence and unexplained infertility.
Conclusions
Midluteal phase endometrium consistently forms NCSs regardless of fertility status, including unexplained infertility. This indicates a possible role for the NCS in initiating the window of endometrial receptivity. However, the consistent presence of NCSs across several different types of infertility challenges the likelihood that inadequate secretory transformation is a cause of infertility.
doi:10.1016/j.fertnstert.2010.10.030
PMCID: PMC3347775  PMID: 21067716
Nucleolar channel system; secretory transformation; receptivity; endometrium; unexplained infertility; immunofluorescence
10.  Circulating Dehydroepiandrosterone Sulfate Levels in Women with Bilateral Salpingo-Oophorectomy during the Menopausal Transition 
Menopause (New York, N.Y.)  2011;18(5):494-498.
Background
A rise in circulating dehydroepiandrosterone sulfate (DHEAS) concentration occurs during the menopausal transition (MT) that is ovarian-stage but not age-related. The objective of this study was to determine the source of the rise in circulating DHEAS.
Methods
Circulating DS concentrations in women that had undergone bilateral salpingo-oophorectomy (BSO) were compared to the pattern of circulating DHEAS in women that progressed through the MT naturally. Annual serum samples from the Study of Women's Health Across the Nation (SWAN) over a ten year study period were used. From1272 women in the SWAN cohort that were eligible for longitudinal evaluation of DHEAS annual samples, eighty one underwent BSO during the pre- or early-perimenopause stage of the menopausal transition and were potentially available for study. Of these eighty one BSO participants, twenty had sufficient annual samples for evaluation of the post-BSO trajectory of circulating DHEAS. SWAN women not having previous hormone replacement therapy those with intact ovaries were compared to women that underwent a BSO immediately after a pre- or early perimenopausal annual visit. There were no intervention and circulating concentrations of DHEAS was the main outcome.
Results
A detectable rise in DHEAS was observed in fourteen (70%) of the twenty BSO women which is similar to the proportion (85%) of women with intact ovaries that had a detectable DHEAS rise. The mean rise in DHEAS (5-8%) was similar in both BSO and non-BSO women.
Conclusion
The MT rise in DHEAS (5-8%) occurring in the absence of ovaries is largely of adrenal origin.
doi:10.1097/gme.0b013e3181fb53fc
PMCID: PMC3123411  PMID: 21178790
Dehydroepiandrosterone sulfate; menopause; adrenal; ovary
11.  Overweight Men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles 
Purpose
To evaluate if elevated male body mass influences success after assisted reproductive technologies
Methods
Retrospective study of 290 cycles.
Results
Male body mass index greater than 25.0 kg/m2 was associated with significantly lower clinical pregnancy (53.2% vs. 33.6%). Multivariable logistic regression indicated that the likelihood of clinical pregnancy was decreased if the male partner was overweight after in vitro fertilization but not after intracytoplasmic sperm injection (odds ratios: 0.21 [0.07–0.69] vs. 0.75 [0.38–1.49], respectively) after adjustment for number of embryos transferred, sperm concentration, female age and body mass.
Conclusion
In this cohort, overweight status of the male partner was independently associated with decreased likelihood of clinical pregnancy after in vitro fertilization but not after intracytoplasmic sperm injection. A detrimental impact of higher male body mass was observed after adjusting for sperm concentration, suggesting that intracytoplasmic sperm injection may overcome some obesity related impairment of sperm-egg interaction.
doi:10.1007/s10815-010-9439-y
PMCID: PMC2965348  PMID: 20635132
Male obesity; In vitro fertilization; IVF/ICSI outcome; Assisted reproduction
12.  Cardiovascular risk factor variation within a Hispanic Cohort: SWAN, the Study of Women’s Health Across the Nation 
Ethnicity & disease  2010;20(4):396-402.
Objectives
Hispanics have less favorable cardiovascular risk profiles relative to other groups, although little is known regarding variability in risk profiles according to country of origin. Our goal was to examine the association of cardiovascular risk factors with country of origin and acculturation in a cohort of middle-aged Hispanic women.
Design
Cross-sectional study.
Setting
Baseline data for participants at the New Jersey Site of the Study of Women’s Health Across the Nation (SWAN).
Participants
419 women (142 non-Hispanic Whites, 277 Hispanic ethnicity: Central American (n=29), South American (n=106), Puerto Rican (n=56), Dominican (n=42) and Cuban (n=44).) aged 42–52.
Main Outcome Measures
BMI, smoking, blood pressure, lipid profiles, and presence of hypertension, hyperlipidemia, diabetes and metabolic syndrome were compared using univariate and multivariable models.
Results
LDL and HDL varied significantly across Hispanic subgroups (overall p ≤ 0.05). Prevalence of metabolic syndrome was greatest in Puerto Rican women (48.2% versus 40.0%, 35.0%, 13.9% and 29.3% in Central American, South American, Dominican and Cuban women, respectively, p=0.016). Central American women were least likely to smoke (p< 0.05 vs. Puerto Rican, Cuban and South American). Prevalence of hypertension and diabetes were similar across groups. Differences in lipids and metabolic syndrome were not explained by acculturation, financial strain, education, physical activity, smoking or dietary fat intake.
Conclusions
There is significant heterogeneity in cardiovascular risk status among middle-aged Puerto Rican, Cuban, Dominican, Central American and South American women, not explained by acculturation or socioeconomic indicators. These differences may be important for targeting screening and preventive interventions.
PMCID: PMC3059124  PMID: 21305828
Cardiovascular Risk Factors; Hispanics; Women; Acculturation
13.  Partial Recovery of Luteal Function after Bariatric Surgery in Obese Women 
Fertility and sterility  2008;92(4):1410.
Objective
To determine whether obesity related reproductive endocrine abnormalities in ovulatory women are reversible with weight loss
Design
Observational cohort study.
Setting
Healthy volunteers in an academic research environment.
Patients
Women age 18–48 with regular menstrual cycles 21–40 days with a BMI ≥ 35 kg/m2 planning to undergo bariatric surgery were recruited.
Intervention
25 eumenorrheic (non-PCOS) women with a mean BMI of 47.3 +/− 5.2 kg/m2 were sampled with daily menstrual cycle urinary hormones prior to (n=25) and 6 months after (n=9) weight loss surgery resulting in >25% reduction initial body weight. Daily hormones were compared pre- and post-operatively, and to 14 normal weight controls.
Main Outcome Measures
LH, FSH, estradiol and progesterone metabolites measured daily for one menstrual cycle. Group means were compared using t-tests among ovulatory cycles.
Results
Luteal Pdg increased from 32.8 ± 10.9 to 73.7 ± 30.5 ug/mgCr (p<0.001) and whole cycle LH increased from 168.8 ± 24.2 to 292.1 ± 79.6 mIU/mgCr (p<0.001) after surgically induced weight loss. Luteal Pdg remained lower than normal weight controls (151.7 ± 111.1 ug/mgCr). Obese women took longer to attain a postovulatory Pdg rise >2mcg/mg creatinine than controls (3.91 ± 1.51 versus 1.71 ± 1.59 days); this improved post-operatively (2.4 ± 1.82 days, p=0.046). Whole cycle E1c was similar to controls at baseline, but decreased after weight loss (from 1026.7 ± 194.2 to 605.4 ± 167.1 ng/mgCr, p<0.001). FSH did not relate to body size in this sample.
Conclusions
Women of very high BMI have deficient luteal LH and Pdg excretion and a delayed ovulatory Pdg rise compared to normal weight women. Although all of these parameters improved with weight loss, Pdg did not approach levels seen in normal weight women. LH may be less effective in stimulating the corpus luteum in obesity. The large postoperative decrease in E1c may reflect the loss of estrone-producing adipose tissue after weight loss.
doi:10.1016/j.fertnstert.2008.08.025
PMCID: PMC2818247  PMID: 18829008
obesity; weight loss; luteal function; LH; FSH; E1c; Pdg; fertility
14.  Lithium chloride treatment induces epithelial cell proliferation in xenografted human endometrium 
Human Reproduction (Oxford, England)  2009;24(8):1960-1967.
BACKGROUND
In mouse endometrium, glycogen synthase kinase-3ß (GSK3ß) is a key enzyme controlling nuclear localization of cyclin D1. We developed a functional model of xenografted human endometrium to test whether similar mechanisms are operative in the human by using Lithium chloride (LiCl), an inhibitor of GSK3ß.
METHODS
Human endometrial samples were obtained from normal volunteers, then implanted under the kidney capsule of nude mice, and treated with estradiol-17ß (E2) or LiCl. Xenografts were assessed for protein expression of MKI-67, mini-chromosome maintenance protein-2, estrogen receptor (ER), progesterone receptor (PR) and cyclin D1.
RESULTS
Both E2 and LiCl induced a robust proliferative response in the epithelium. Only lithium treatment produced clear nuclear localization of cyclin D1 consistent with the proliferative response observed. Regenerated endometrium had detectable ER and PR expression.
CONCLUSION
Xenografted human endometrium provides a dynamic model of uterine biology. Administration of LiCl in the absence of E2 induced epithelial proliferation, supporting the hypothesis that human and murine endometrial proliferation may share key regulatory pathways. These data suggest a possible link between the increased menstrual disturbances in women with affective disorders taking lithium and the consequent potential for the development of endometrial proliferative disorder.
doi:10.1093/humrep/dep115
PMCID: PMC2710285  PMID: 19403565
estrogen; progesterone; cell cycle; endometrium; lithium
15.  Nuclear pore complex proteins mark the implantation window in human endometrium 
Journal of cell science  2008;121(Pt 12):2037-2045.
Summary
Nucleolar channel systems (NCSs) are membranous organelles appearing transiently in the epithelial cell nuclei of postovulatory human endometrium. Their characterization and use as markers for a healthy receptive endometrium have been limited because they are only identifiable by electron microscopy. Here we describe the light microscopic detection of NCSs using immunofluorescence. Specifically, the monoclonal nuclear pore complex antibody 414 shows that NCSs are present in about half of all human endometrial epithelial cells but not in any other cell type, tissue or species. Most nuclei contain only a single NCS of uniform 1 μm diameter indicating a tightly controlled organelle. The composition of NCSs is as unique as their structure; they contain only a subset each of the proteins of nuclear pore complexes, inner nuclear membrane, nuclear lamina and endoplasmic reticulum. Validation of our robust NCS detection method on 95 endometrial biopsies defines a 6-day window, days 19-24 (±1) of an idealized 28 day cycle, wherein NCSs occur. Therefore, NCSs precede and overlap with the implantation window and serve as potential markers of uterine receptivity. The immunodetection assay, combined with the hitherto underappreciated prevalence of NCSs, now enables simple screening and further molecular and functional dissection.
doi:10.1242/jcs.030437
PMCID: PMC2657873  PMID: 18505792
Human reproduction; Nuclear envelope; Nuclear organelle

Results 1-15 (15)