Preconception counseling: do patients learn about genetics from their obstetrician gynecologists?

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal antimullerian hormone levels do not predict fetal aneuploidy.

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.

Cyclic regulation of transcription factor C/EBP beta in human endometrium.

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.

A multiple marker model to predict pregnancy viability when progesterone is indeterminate.

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 under 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 (AUC = 0.90). CONCLUSION: A multiple marker model predicted pregnancy viability in symptomatic women with overall accuracy of 90%.

G protein-coupled estrogen receptor (GPER) expression in normal and abnormal endometrium.

Rapid estrogen effects are mediated by membrane receptors, and evidence suggests a role for both a membrane-associated form of estrogen receptor alpha (ESR1; ERα) and G-protein coupled receptor 30 (GPER; GPR30). Considering estrogen's importance in endometrial physiology and endometriosis pathophysiology, we hypothesized that GPER could be involved in both cyclic changes in endometrial estrogen action and that aberrant expression might be seen in the eutopic endometrium of women with endometriosis. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis of normal endometrium, endometrial samples demonstrated cycle-regulated expression of GPER, with maximal expression in the proliferative phase. Eutopic and ectopic endometrium from women with endometriosis overexpressed GPER as compared to eutopic endometrium of normal participants. Ishikawa cells, an adenocarcinoma cell line, expressed GPER, with increased expression upon treatment with estrogen or an ESR1 agonist, but not with a GPER-specific agonist. Decreased expression was seen in Ishikawa cells stably transfected with progesterone receptor A. Together, these data suggest that normal endometrial GPER expression is cyclic and regulated by nuclear estrogen and progesterone receptors, while expression is dysregulated in endometriosis.

The impact of smoking on antimüllerian hormone levels in women aged 38 to 50 years.

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.

A case report of successful pregnancy in a patient with pure 46,XY gonadal dysgenesis.

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.