Association study of androgen signaling pathway genes in polycystic ovary syndrome.

OBJECTIVE: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). DESIGN: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters. SETTING: Tertiary referral center. PATIENT(S): Discovery cohort: 354 women with PCOS and 161 control women. Replication cohort: 397 women with PCOS and 306 control women. INTERVENTION(S): Phenotypic and genotypic assessment. MAIN OUTCOME MEASURE(S): Single-nucleotide polymorphism genotypes, association with PCOS status, and androgenic and metabolic parameters. RESULT(S): In the discovery cohort, FKBP4 SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS. This finding was not confirmed in the replication cohort analysis; however, when combining the two cohorts, rs4409904 was associated with lower odds of PCOS. In subjects with PCOS in the replication cohort as well as in the combined cohort, rs2968909 was associated with lower body mass index. CONCLUSION(S): Single-nucleotide polymorphisms in FKBP4, which codes for the AR co-chaperone FKBP52, may be associated with PCOS and body mass index in patients with PCOS. The remaining genes studied do not seem to be major contributors to the development of PCOS. These findings warrant confirmation in future studies, and genes encoding other androgen pathway components remain to be studied.

Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality.

PURPOSE: To determine the expression of SMAD transcripts in human granulosa cells. METHODS: Luteinized mural granulosa cells were harvested from forty women undergoing oocyte retrieval, and RNAs were isolated. SMAD expression levels were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (q-RTPCR). RESULTS: SMAD1-7 and 9 are expressed in human granulosa cells, with SMAD2, 3 and 4 showing the highest expression levels. Peak estradiol (E2) levels correlated with the number of oocytes retrieved during IVF. Oocyte number showed no correlation with SMAD expression levels or ratios. Fertilization rates also did not correlate with the expression levels of individual SMADs, but did correlate with higher SMAD4:SMAD3 ratios (p = 0.0062) and trended with SMAD4:SMAD2 (p = 0.0698). CONCLUSIONS: SMAD transcripts are differently expressed in human granulosa cells, where they may mediate TGF-beta superfamily signaling during folliculogenesis and ovulation. Further, the relative expression ratios of SMAD2, 3 and 4 may differentially affect fertilization rate.

Fifteen-year trend in the use of male reproductive surgery: analysis of the healthcare cost and utilization project data.

OBJECTIVE: • To determine trends in male reproductive surgeries. MATERIALS AND METHODS: • A database analysis was performed using the Healthcare Cost and Utilization Project databases from 1988, 1992 and 1998-2002. SAS statistical software was used to estimate the total numbers of reproductive surgeries and their variances for each year. RESULTS: • The number of male reproductive surgeries has declined during the period of study, both in the inpatient and outpatient arenas. The number of procedures with a diagnosis of infertility has also declined. CONCLUSION: • The number of male reproductive surgeries has declined from 1988 to 2002.

Fifteen-year trend in the use of reproductive surgery in women in the United States.

OBJECTIVE: To determine trends in female reproductive surgery volume. DESIGN: Database analysis using the Healthcare Cost and Utilization Project databases from 1988, 1992, 1998, and 2002. SETTING: Academic medical center. PATIENT(S): All patients who underwent reproductive surgeries using United States community hospital discharge data and inpatient and outpatient data for New Jersey (NJ) and Maryland (MD). INTERVENTION(S): SAS statistical software was used to estimate the number of reproductive surgeries per year; weighted least squares analysis was performed to estimate trends in surgeries. MAIN OUTCOME MEASURE(S): Number of reproductive surgeries. RESULT(S): Nationally, approximately 250,000 inpatient female reproductive surgeries are performed yearly. There was a modest decreasing trend (-17%) in total reproductive surgeries, and the number of procedures with an associated diagnosis of infertility declined 79%; neither change reached statistical significance. Alternatively, a significant decline occurred in surgeries of the fallopian tubes and ovaries. Likewise, inpatient surgeries were unchanged in NJ and actually increased in MD (+13%), although outpatient surgeries declined in both states (-12% and -37%, respectively). CONCLUSION(S): The increased use of assisted reproductive technology (ART) has coincided with a decrease in surgeries on the fallopian tubes and ovaries. With the exception of surgery for tubal infertility, reproductive surgery has largely been complementary to, rather than replaced by, ART.

Expression of forkhead transcription factors in human granulosa cells.

Members of the forkhead box O1 (FOXO) family of transcription factors are expressed in granulosa cells during various stages of follicle development, and evidence from rodent and other model systems suggests that they may be involved in regulating follicular activation and oocyte maturation. In this report, we show that FOXO1, FOXO3, and FOXO4 are expressed in human luteinized mural granulosa cells, which may suggest that these transcription factors are also involved in human folliculogenesis and luteinization.