Global gene expression in the human fetal testis and ovary.

This study describes a temporal profile of gene expression from normal human fetal testes and ovaries. Gonads from 34 fetuses between 9 wk and 20 wk of gestation were obtained from the Department of Pathology and the Birth Defects Research Laboratory at the University of Washington. Relative transcript levels were determined using the Affymetrix Human Genome U133A Plus 2.0 arrays. Sex determination occurs in the human gonad at approximately 6 wk of gestation with development of the testis driven by expression of SRY. In this study, SRY transcript was present and elevated at 9 wk of gestation in the testis but was absent in the ovary. The transcript levels of other testis-specific factors SOX9 and AMH and the steroidogenic genes CYP17A1, CYP11A1, STAR, and HSD17B3 were all significantly higher in the testis. In contrast, transcripts known to be involved in meiosis, including STRA8, SPO11, SYCP3, TEX11, TEX14, and STAG3, showed highest expression in the fetal ovary beginning at Week 12. These gene expression profiles will be a resource for understanding and defining normal gonad development and provide the opportunity to dissect abnormal development.

Use of the Interview in Resident Candidate Selection: A Review of the Literature.

BACKGROUND: Although the resident candidate interview is costly and time-consuming for both applicants and programs, it is considered critically important for resident selection. Noncognitive attributes, including communication skills and professionalism, can be assessed by the personal interview. OBJECTIVE: We conducted a review of the literature on the residency interview to identify the interview characteristics used for resident selection and to ascertain to what extent the interview yields information that predicts future performance. METHODS: We searched PubMed and Scopus using the following search terms: residency, internship, interview, selection, and performance. We extracted information on characteristics of the interview process, including type of interview format, measures taken to minimize bias by interviewers, and testing of other clinical/surgical skills. RESULTS: We identified 104 studies that pertained to the resident selection interview, with highly varied interview formats and assessment tools. A positive correlation was demonstrated between a medical school academic record and the interview, especially for unblinded interview formats. A total of 34 studies attempted to correlate interview score with performance in residency, with mixed results. We also identified a number of studies that included personality testing, clinical skills testing, or surgical skills testing. CONCLUSIONS: Our review identified a wide variety of approaches to the selection interview and a range of factors that have been studied to assess its effectiveness. More research needs to be done not only to address and ascertain appropriate interview formats that predict positive performance in residency, but also to determine interview factors that can predict both residents' "success" and program attrition.

Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?

This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase.

Age-related analysis of inhibin A, inhibin B, and activin a relative to the intercycle monotropic follicle-stimulating hormone rise in normal ovulatory women.

Previous studies have reported that the monotropic rise in FSH in older women is associated with decreased inhibin B and/or A levels and increased levels of activin A. Whereas most investigators have found decreased follicular-phase inhibin B, the roles of inhibin A and activin A as modulators of the FSH rise are unclear. The objectives of this study were to determine whether deficiencies in circulating levels of inhibin A, inhibin B, and/or activin A exist during the intercycle interval in ovulatory older (age, 40-45 yr; n = 16), compared with younger women (age, 20-25 yr; n = 13). Blood samples were obtained daily throughout one menstrual cycle and the follicular phase of the subsequent cycle and were analyzed for LH, FSH, estradiol, inhibin A and B, and activin A. Despite significant FSH elevation, no deficiencies in inhibin A, activin A, or estradiol were detected in older subjects. In fact, inhibin A was significantly higher in older participants during the intercycle phase (P = 0.01), whereas inhibin B was significantly lower. Thus, the monotropic rise in FSH does not appear to result from changes in inhibin A or activin A, supporting the concept that inhibin B plays a critical role in mediating the FSH rise in older women.

Factors influencing pregnancy rates with a combined clomiphene citrate/gonadotropin protocol for non-assisted reproductive technology fertility treatment.

OBJECTIVE: To determine the effectiveness of a combined clomiphene citrate/gonadotropin protocol in a general infertility population and to evaluate factors influencing pregnancy rates obtained with this protocol. DESIGN: A retrospective chart review. SETTING; University-based infertility clinic. PATIENT(S): Two hundred forty-eight patients undergoing 658 cycles of minimal stimulation (MS) protocol from 1996-2000. INTERVENTION(S): Patients underwent treatment with clomiphene citrate and gonadotropin, often followed by intrauterine insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Overall, the clinical pregnancy rate was 7.1% per cycle (n = 248 patients and 658 cycles). The age range of the patients was 24-47 years (mean +/- SD = 36.5 +/- 4.9) with 8.7% noted to have ovulatory dysfunction. Pregnancy rates varied significantly (P<.05) with patient age (9.3% in women <40 years vs. 2.4% in women > or =40), duration of infertility (9.0% in women with < or =3 years of infertility vs. 2.2% in women with >3 years of infertility) and number of follicles produced during stimulation (9.1% in women with > or =3 follicles vs. 4.6% in women with <3 follicles). CONCLUSION(S): The effectiveness of the MS protocol in a general infertility population with a predominantly ovulatory status is much less than that previously reported in a younger patient population with a significant rate of ovulatory dysfunction. This protocol does not appear to lead to pregnancy rates higher than that reported for clomiphene citrate/intrauterine insemination (IUI) cycles. The clinical pregnancy rates using a minimal stimulation protocol are particularly compromised in women over 40, those with a longer duration of infertility or those who produce few follicles during stimulation.