BACKGROUND: Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data.OBJECTIVE: The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle.STUDY DESIGN: Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation.RESULTS: Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum.CONCLUSION: Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (< 120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample.

Objective: To determine whether levels of antimullerian hormone (AMH) in serum vary during the normal menstrual cycle, using the most recently developed immunoassay method.Design: Prospective cohort study.Setting: Local community.Patient(s): Women with normal menstrual cycles and between the ages of 18 and 45 years were recruited (n = 45). Blood samples were collected on 5 days within each cycle: two in the follicular phase and three after confirmed ovulation. Exclusion criteria were anovulatory cycles, incomplete sample collection, insufficient blood volume, or non-Caucasian ethnicity.Intervention(s): None.Main Outcome Measure(s): Serum samples were tested for levels of AMH using a new immunoassay method (Ansh Labs). The effects of body mass index (BMI) and smoking on serum AMH levels were considered.Result(s): Serum AMH levels varied significantly during the menstrual cycle, with the highest levels in the follicular phase. When the analysis was stratified by age, AMH variation during the menstrual cycle was significant only for women older than 30 years. Serum AMH levels were not significantly altered by BMI or smoking.Conclusion(s): The new AMH immunoassay revealed a follicular phase rise in serum levels, particularly in women over the age of 30 years. This is consistent with other reports finding an interaction of menstrual cycle variation in AMH and chronological age. Nonetheless, the extent of variation is small, and sampling on any day of the menstrual cycle is expected to adequately reflect ovarian reserve. (C) 2016 by American Society for Reproductive Medicine.

The purpose of this observational survey study is to assess genetic knowledge in reproductive-aged women and to determine the role played by their obstetricians in their education. A 31-item survey was distributed via an internet survey service to women between the ages of 18 and 45. The survey included subject demographics, a query regarding the source of subjects’ knowledge of genetics, and 6 question genetics quiz with 3 fundamental questions and 3 advanced questions. Subjects were divided into parous and nulliparous groups, and responses were compared using student’s t-test for continuous variables and chi square for proportions. Participants included 207 parous and 221 nulliparous women. There were no differences in demographic characteristics including age and education. Parous women scored significantly higher than nulliparous women on the fundamental genetics quiz (71 vs 61 %, p = 0.03). This difference remained but was no longer significant when the 3 advanced questions were included (48 vs 42 %). Only 39 % of parous and 8 % of nulliparous subjects listed their physician as one of their main sources of genetic information. 78 % of all subjects stated that they would prefer to receive genetic information from their physicians over other sources. Recently parous women scored higher on a genetics assessment quiz than did their nulliparous counterparts, but the majority did not cite their obstetrician gynecologists as a main source of information. As genetic counseling and testing are becoming increasingly important aspects of obstetrical care, obstetricians should play a more substantial role in educating their patients.

INTRODUCTION: There is a common perception that physicians cannot achieve a work–life balance. A survey was conducted to ascertain whether physicians have children and, if so, when and whether they encourage their children to follow in their footsteps. METHODS: A survey titled “Would you encourage your children to become physicians?” was sent to current residents, fellows, and attendings. The study was approved by the institutional review board at Tufts Medical Center. The FREQ procedure and χ2 tests were used for data analysis. RESULTS: Eight hundred one responses were received. 85.2%, 60%, and 30.3% of the attendings, fellows, and residents who responded and who have children, respectively. Male residents were more likely to have children than females (42.2% compared with 20.2%, P<.001). No sex differences were seen among attendings with children (males compared with females: 88.1% compared with 82.2%, P=.14) or fellows with children (males compared with females: 69.2% compared with 55.6%, P=.41). Surgical attendings, including obstetricians and gynecologists, were more likely to encourage their children to become physicians compared with medical specialties (71.4% compared with 56.6%, P=.02). There was no difference in encouragement among residents. Of physicians with sons and daughters, 39.4% would encourage both sexes to become doctors and 39.4% would encourage neither. Of the remaining 21.2% with both daughters and sons, more respondents preferentially encourage their son compared with their daughter to pursue medicine (13.9% compared with 7.2%, P=.08). CONCLUSIONS: Our survey suggests that physicians can achieve work–life balance. Family-building is a priority for the majority of physicians, although many delay parenthood until after residency.

Premature ovarian failure (POF), also called primary ovarian insufficiency (POI), is defined as irregular menses in women younger than 40 years with menopausal-level serum gonadotropins [1]. Spontaneous onset POF may result from numeric and structural chromosomal abnormalities, fragile X premutations, autoimmune disorders and rare syndromes, though in most cases the etiology remains unknown [2]. Structural chromosomal abnormalities, such as deletions and translocations of specific regions on the X chromosome, have been associated with POF. This association may be due to the haploinsufficiency of genes necessary for normal ovarian function. Standard karyotypes and deletion mapping have identified three regions of interest for POI, one in Xp and two in X (POF1: X26-28 and POF2: X13.3-22) [3, 4]. Several candidate genes in X have been proposed by mapping genes interrupted by the breakpoints in X;autosome translocations. These candidate genes include DIAPH2, XPNEP2, DACH2, POF1B, CHM and NXF5, though none of these genes have a well-defined role in POF [5]. Introduction of high-resolution microarray CGH has refined the ability to detect cryptic chromosomal deletions and duplications in the X POF regions, potentially facilitating identification of candidate genes [6]. We present a patient with infertility and primary ovarian insufficiency having a balanced Xq;autosome translocation near the POF2 region, with a cryptic deletion at Xq27.2, identified with array CGH and confirmed by fluorescent in situ hybridization (FISH). The deletion corresponds to the loci for SPANX (sperm protein associated with the nucleus, X-linked), which play roles in spermatogenesis and may represent candidate genes for POF.

Purpose To determine if diminished ovarian reserve (measured by maternal antimullerian hormone (AMH) levels), is associated with fetal aneuploidy (determined by prenatal karyotype). Methods This case-control study included 213 women with singleton pregnancies who underwent both serum aneuploidy screening and invasive prenatal diagnosis. 18 patients carrying an aneuploid fetus served as cases and the remaining 195 women with a euploid fetus were controls. Serum AMH was measured using two assays: AMHbc (Beckman-Coulter) and AMHdsl (Diagnostic Systems Laboratories). Karyotypes were determined by chorionic villus sampling or amniocentesis. Results AMHbc levels did not differ between women with an aneuploid fetus and women with a euploid fetus ( p = 0.46) and did not predict aneuploidy (ROC Area = 0.57). Additionally, AMHbc values declined significantly with advancing gestational age. Conclusions Maternal AMH does not appear to be a marker of fetal aneuploidy in ongoing pregnancies. Contrary to previous reports, we found a significant decline in maternal AMH levels with advancing gestational age.

Objective: Smoking is associated with increased follicle-stimulating hormone levels and early menopause. Smoking may directly accelerate ovarian follicular depletion or may act indirectly by increasing the pituitary production of follicle-stimulating hormone. Antimüllerian hormone (AMH), produced by ovarian follicles, is a more direct measure of ovarian reserve. The objective of our study was to determine the extent to which smoking influences ovarian reserve, as measured by AMH levels. Methods: A community sample of 284 women aged 38 to 50 years completed a self-administered questionnaire including a detailed smoking history. Serum AMH levels were measured on day 2, 3, or 4 of the menstrual cycle. The association between AMH and smoking was analyzed using linear regression, adjusting for age and body mass index. Results: Participants aged 38 to 42, 43 to 45, and 46 to 50 years had geometric mean AMH values of 6.7 pM (95% CI, 5.2-8.7 pM), 2.7 pM (95% CI, 1.9-3.8 pM), and 1.3 pM (95% CI, 1.0-1.7 pM), respectively. Current smokers, but not past smokers, had 44% lower AMH values than did the reference group (participants with neither active nor former or passive smoke exposure; P = 0.04). Passive smoking had no effect on AMH values when compared with the reference group (P = 0.55). The impact of smoking on AMH values was not dose dependent based on cigarettes per day (P = 0.08) or pack-years (P = 0.22). Finally, prenatal exposure to smoking (either maternal or paternal) had no impact on AMH levels (P = 0.47 and P = 0.89, respectively). Conclusions: Active smoking, but not former smoking, is associated with decreased AMH values in late-reproductive-age and perimenopausal women, suggesting a possible direct effect of smoking on the depletion of the antral but not primordial follicles. The direct impact of active smoking on AMH levels in younger women requires further investigation.

Objective: To report a successful pregnancy in a patient with pure 46,XY gonadal dysgenesis.Design: Case report.Setting: Academic reproductive endocrinology and infertility unit.Patient(s): A patient with pure 46,XY gonadal dysgenesis and a desire to become pregnant.Intervention(s): Laparoscopic gonadectomy, in vitro fertilization using donor oocytes, transfer of cryopreserved blastocysts, and cesarean delivery.Main Outcome Measure(s): Successful pregnancy and live birth. Result(s): Successful pregnancy and delivery of a healthy infant following in vitro fertilization using donor oocytes and embryo transfer.Conclusion(s): With the use of donor oocytes, patients with pure 46, XY gonadal dysgenesis can anticipate successful pregnancy. (Fertil Steril (R) 2008;90:2015.e1-e2. (C) 2008 by American Society for Reproductive Medicine.)

Background The transcription factor CCAAT/enhancer-binding protein (C/EBP) beta is a critical mediator of murine endometrial function during embryo implantation. Our objective is to characterize changes in C/EBP beta mRNA abundance and protein localization over the normal human menstrual cycle. Methods Fifty normally cycling volunteers without reproductive disorders were randomized to undergo endometrial sampling on a specific cycle day, with secretory phase samples timed using urinary LH surge. Samples were assessed for relative C/EBP beta mRNA expression using quantitative real-time RT-PCR and for C/EBP beta protein localization using immunohistochemistry. The semiquantitative histologic scoring (HSCORE) system was used to compare staining intensity in each tissue compartment between each cycle phase. Results C/EBP beta mRNA expression by whole endometrium peaks in the late secretory phase and is significantly higher than that in the proliferative and mid-secretory phases. A marked increase in nuclear C/EBP beta protein immunostaining is seen in stromal cells beginning about cycle day 20, coincident with the start of endometrial receptivity. This increased staining continues for the remainder of the cycle. Conclusion In the normal human menstrual cycle, C/EBP beta mRNA and protein expression also change, with increased nuclear immunostaining in the mid-secretory phase, suggesting a possible role for C/EBP beta in human endometrial receptivity.

OBJECTIVE: To develop a model to differentiate viable from nonviable pregnancies at a single first-trimester visit.STUDY DESIGN: This prospective cohort study included 256 symptomatic women in the first trimester who presented to our urgent care unit in Providence, Rhode Island, between 2002 and 2004. Predictors of pregnancy viability were collected, including clinical information and serum samples for several biomarkers. Each predictor was evaluated alone and in conjunction with other variables using receiver operator characteristic curves. The cohort was separated into 2 subgroups based on whether the progesterone value was at the "extremes" (< 5 ng/mL or > 25 ng/mL) or in the "grey zone" (5-25 ng/mL).RESULTS: Among single biomarkers, progesterone had the greatest diagnostic accuracy in predicting viability. Progesterone was highly accurate at the extremes (area tinder the curve [AUC] = 0.99) but less accurate in the grey zone (AUC = 0.71). A multiple marker model was developed to include progesterone for all patients, and human chorionic gonadotropin, ultrasound findings and symptoms for participants in the grey zone (A UC = 0. 90).CONCLUSION: A multiple marker model predicted pregnancy viability in symptomatic women with overall accuracy of 90%.