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Objective To evaluate whether women with the polycystic ovary syndrome (PCOS) have an increased rate of elevated serum levels of common autoimmunologic parameters. Design Prospective case-control study. Setting Academic research institution. Patient(s) One hundred nine women with PCOS and 109 age-matched healthy controls. Intervention(s) Peripheral venous puncture, ultrasonography, questionnaire. Main Outcome Measure(s) Serum levels of antinuclear antibodies (ANAs) were measured by immunometric enzyme immunoassay, serum levels of IgG class autoantibodies against histone, IgG class autoantibodies against nucleosomes, and IgG class autoantibodies against double-stranded (ds) DNA were measured by enzyme immunoassays. Result(s) Women with PCOS had significantly elevated serum levels of antihistone and anti-dsDNA antibodies, whereas serum levels of ANAs and antinucleosome antibodies were similar between the two groups. When serum levels of ANAs, antihistone, antinucleosomes, and anti-dsDNA antibodies were correlated with clinical and biochemical parameters, a significant correlation between serum levels of ANAs and serum TSH was established. Conclusion(s) Our study shows that serologic parameters of autoimmunity (i.e., antihistone and anti-dsDNA antibodies) are elevated in women with PCOS. A role of autoimmunologic processes in PCOS can be suspected.

Objective Persistent Chlamydia trachomatis infections are associated with tubal pathology. We studied whether sampling from multiple sites would increase the identification of the infections. Design Prospective cohort study. Setting Tertiary care facility. Patient(s) Two hundred two infertile women. Intervention(s) Smears were taken from the cervix, urethra, high vagina, fimbriae and the Douglas cavity. Blood samples were collected and tubal patency was assessed by pertubation with lipiodol and methylene blue. Main Outcome Measure(s) Detection of C. trachomatis DNA, detection of IgA and IgG antibodies against C. trachomatis, and antibodies against chlamydial heat-shock protein 60, tubal patency. Result(s) Chlamydia trachomatis was detected in 2 of 202 patients, for an overall prevalence of 1%. In both patients PCR results were positive in the cervical, vaginal, and urethral specimens. Chlamydia trachomatis IgG, IgA, and chlamydial heat-shock protein 60 IgG were significantly more prevalent in women with distal tubal pathology than in those without (26/40 [65.0%] vs. 16/162 [9.9%], 9/40 [22.5%] vs. 7/162 [4.3%], and 34/40 [85.0%] vs. 34/162 [21.0%]). Bacterial colonization was found in 1 of 202 samples from the Douglas cavity. Conclusion(s) Routine DNA testing for C. trachomatis should be confined to cervical sampling. The association between tubal pathology and seropositivity of IgG, IgA, and cHSP60 IgG was confirmed but did not add clinically valuable information during the diagnostic workup of infertility patients.

In a cross-sectional study of 2,802 perimenopausal caucasian women, carriage of at least one mutated allele of the 17-alpha-hydroxysteroid dehydrogenase type 1 (17-alpha HSD) vlV A--C single nucleotide polymorphism (SNP) was associated with a significantly increased body mass index (mean 24.3 +/- 4.4 kg/m(2) vs. 23.5 +/- 4.2 kg/m(2); P.001), and obesity was more frequent among mutant allele carriers (P=.06; odds ratio 1.38; 95% confidence interval 0.97-1.95), providing evidence of 17-alpha HSD as a candidate gene of perimenopausal obesity.

Objective To establish the prevalence of endometriosis metastatic to pelvic sentinel lymph nodes (PSLN) in women with ovarian and/or peritoneal endometriosis. Design Prospective clinical study. Setting Academic research institution. Patient(s) Women with a laparoscopic diagnosis of ovarian and/or peritoneal endometriosis verified by intraoperative frozen section analysis. Intervention(s) Resection of endometriotic lesions and PSLN after cervical blue dye injection. Main Outcome Measure(s) Histologic analysis of PSLN for the presence of endometriosis and immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK), and CD-10 expression. Result(s) The study enrolled 26 women with suspected endometriosis; endometriosis was confirmed in 23 women, and a PSLN was identified in 19 women. A total of 37 (right side: 20; left side: 17) lymph nodes were removed. The prevalence of endometriotic lesions in PSLN was 11% (2 of 19). Both lesions were positive for ER, PR, CK, and CD-10. Isolated endometriotic-like cells (IELCs) staining positive for ER and PR were identified in the peripheral sinus of 16 (80%) of 20 and 14 (70%) of 20 PSLN, respectively. All IELCs lacked CK staining, whereas CD-10 staining was present in 16 (80%) of 20 cases, indicating a stromal origin of IELCs. Intraoperative and/or postoperative complications were observed in 1 (5%) of 19 women. Conclusion(s) Spread of IELCs to PSLN is common in ovarian and/or peritoneal endometriosis. Metastatic lesions in PSLN are present in 11% of women. Further studies to evaluate the prognostic and predictive value of endometriotic spread to PSLN are warranted.

Objective To establish an association between the number of oocytes retrieved after controlled ovarian hyperstimulation (COH) and saliva cortisol (F) levels, as well as subjective stress, in women undergoing their first IVF cycle. Design Prospective clinical study. Setting Academic research institution. Patient(s) Women with primary or secondary infertility undergoing IVF. Intervention(s) Fertility problem inventory (FPI) questionnaire and measurement of morning and evening saliva F by RIA. Main Outcome Measure(s) Number of oocytes and stress, defined as low morning F and/or a positive FPI result. Result(s) Eighty-three women provided saliva specimens, 66 of whom also filled in the FPI. The median number of oocytes was 8.4 (range 0–26). A state of stress was observed in 38/83 (46%) women. The mean number of oocytes was not significantly different between women with and without stress (7.3 ± 4.3 vs. 8.9 ± 6.9, respectively). In a multivariate analysis, stress (odds ratio 2.6; 95% confidence interval 0.03–225.7) and morning F (odds ratio 0.9; 95% confidence interval 0.6–1.3) were not significantly associated with the number of oocytes. There were no statistically significant correlations between F concentrations, FPI results, and age, number of poor responders, live birth rate, and clinical pregnancy rate (PR). Conclusion(s) Stress, as measured by saliva F and the FPI questionnaire, does not negatively impact the effectiveness of COH and is not associated with a reduced number of oocytes.

Objective To evaluate the incidence of venous thromboembolism (VTE) in transsexual patients and the value of screening for thrombophilia in this population. Design Retrospective cohort study. Setting Academic research institution. Patient(s) Two hundred fifty-one transsexuals (162 male-to-female [MtF] and 89 female-to-male [FtM] transsexuals). Intervention(s) Screening for activated protein C (aPC) resistance, antithrombin III, free protein S antigen, and protein C deficiency. Main Outcome Measure(s) Incidence of thrombophilic defects and VTE during cross-sex hormone therapy. Result(s) Activated protein C resistance was detected in 18/251 patients (7.2%), and protein C deficiency was detected in one patient (0.4%). None of the patients developed VTE under cross-sex hormone therapy during a mean of 64.2 ± 38.0 months. There was no difference in the incidence of thrombophilia comparing MtF and FtM transsexuals (8.0% [13/162] vs. 5.6% [5/89], respectively). Conclusion(s) VTE during cross-sex hormone therapy is rare. General screening for thrombophilic defects in transsexual patients is not recommended. Cross-sex hormone therapy is feasible in MtF as well as in FtM patients with aPC resistance.

Objective To systematically monitor the frequency and risk factors of adverse events (AEs) in a reproductive surgery endoscopy unit. Design Prospective cohort study. Setting Academic research institution. Patient(s) All consecutive surgical patients of a reproductive surgery unit from December 2005 to March 2007. Intervention(s) Monitoring for predefined AEs by trained observers. Main Outcome Measure(s) Number of preventable and not preventable AEs, medical errors, and system problems. Univariate analysis and multivariate logistic regression were used to identify risk factors of AEs. Result(s) Seven hundred ninety-six women were included. We identified 60 AEs in 45 patients (risk 6%; 95% confidence interval [CI] 1%–11%). Adverse events were postoperative fever (n = 1), wound breakdown (n = 1), intraoperative or postoperative administration of packed erythrocytes (n = 6), surgical revision (n = 7), unplanned readmission (n = 5), transfer to intensive care unit (n = 1), conversion (n = 8), intraoperative organ injury (n = 9), blood loss >500 mL (n = 3), surgery canceled (n = 15), and other AEs (n = 4). Six patients (risk 0.8%; 95% CI 0–2%) had multiple AEs. One (0.01%) and 11 (1.4%) AEs were deemed due to medical errors and system problems, respectively. Twelve and 48 AEs were deemed preventable and not preventable, respectively. In a univariate and multivariate analysis, only duration of surgery (odds ratio 3.78; 95% CI 1.95–7.33) was significantly associated with having an AE. Conclusion(s) Clinical outcome monitoring is a useful tool for assessing the outcome quality of reproductive surgery by identifying potentially preventable AEs and associated risk factors.

In a prospective case-control study of 127 normozoospermic and 435 non-normozoospermic Caucasian men, the genotype frequencies of a polymorphism of the interleukin-1 beta gene (IL-1beta Taq C--T) were statistically significantly different between groups (homozygous wild-type C/C [57%], heterozygous C/T [42%], and homozygous mutant T/T [1%] vs. C/C [57%], C/T [36%], T/T [7%] for normozoospermic and non-normozoospermic men, respectively; odds ratio, 4.8; 95% confidence interval, 1.13 to 20.28). This association was restricted to men with the oligoasthenoteratozoospermia (OAT) syndrome. We conclude that the investigated polymorphism is associated with sperm pathology in Caucasians.

Objective To review clinical studies assessing the effect of phytoestrogen supplementation on the signs and symptoms of the climacteric syndrome and on the incidence of breast cancer, cardiovascular disease, and skeletal fractures. Design Literature research using PubMed and the Cochrane controlled trials register. Setting None. Patient(s) None. Intervention(s) None. Main Outcome Measure(s) None. Result(s) Six systematic reviews and meta-analyses of 25 randomized, controlled trials (RCTs) assessing the use of phytoestrogens for the treatment of the climacteric syndrome were identified. Systematic reviews of RCTs show contradictory results, and meta-analyses demonstrate no statistically significant reduction of vasomotor symptoms for phytoestrogens. Individual RCTs report significant reductions in vasomotor symptoms for red clover and soy phytoestrogens. In selected patient populations, such as in women with early natural postmenopause and mild to moderate vasomotor symptoms, a systematic review of five RCTs found a significant reduction of hot flashes in five out of five RCTs. Twenty-two case-control and cohort studies examined the incidence of breast cancer among women with and without a diet high in phytoestrogens. A meta-analysis of 21 studies found a significantly reduced incidence of breast cancer among past phytoestrogen users. RCTs document beneficial effects of phytoestrogens on surrogate parameters such as bone mineral density, vasodilation, platelet aggregation, insulin resistance, and serum concentrations of triglycerides, high-density lipoprotein, and low-density lipoprotein. None of the available RCTs documents a protective effect of phytoestrogens for the clinical end points of breast cancer, bone fracture, or cardiovascular events. Conclusion(s) Based on the available evidence, phytoestrogens should only be used in selected women, i.e., those presenting with mild to moderate vasomotor symptoms in early natural postmenopause. None of the compounds investigated so far have been proven to protect against breast cancer, bone fracture, or cardiovascular disease.

Objective To summarize the existing experience with the use and success rate of assisted reproductive techniques (ART), in particular testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI), in Klinefelter patients. Design A systematic review of the literature, including all published case reports to date. Patient(s) Thirty-nine reported successful pregnancies fathered by nonmosaic Klinefelter patients. Main outcome measure(s) The overall risk of transmitting a chromosomal abnormality to the offspring of Klinefelter patients. Result(s) In nonmosaic and mosaic Klinefelter patients, chromosomally normal sperm cells can be extracted from testicular tissue and used for ICSI. Conclusion(s) The application of ART to Klinefelter patients can be recommended as a method to achieve reproduction in this selected infertility patient cohort.

Objective: To investigate the relationship between idiopathic recurrent miscarriage (IRM) and two polymorphisms of intron 2 of the gene-encoding interleukin–1 receptor antagonist, an autochthonous modulator of the proinflammatory immune response. Materials and Methods: One hundred five women with a history of three or more consecutive pregnancy losses before 20 weeks of gestation and 91 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss were investigated. Polymerase chain reaction was performed to identify the wild-type allele (allele 1) and two polymorphic alleles (alleles 2 and 3) of the interleukin–1 receptor antagonist gene. Results: Allele frequencies among women with IRM and controls were 0.34 and 0.11, respectively, for allele 2 (P = 0.002; odds ratio: 7.4, confidence interval: 2.9–10.8) and 0.05 and 0.05, respectively, for allele 3 (P = 0.6; odds ratio: 1.3, confidence interval: 0.8–2.3). Allele 2 was present in homozygous form (IL–1 RA 2/2) in 9% of women with IRM. In contrast, 1% of the control women were homozygous for this allele (P