Physical Activity and Changes in White Matter Hyperintensities over Three Years.

OBJECTIVES: Since physical activity (PA) has demonstrated benefits for cardiovascular health, it is possible to hypothesize that higher or increasing PA slows the progression of white matter hyperintensities (WMH). We investigated the association between PA and the progression of WMH in non-demented older adults with memory complaints. DESIGN: We included 152 participants (mean age 74.7±3.8 years; 63.8% women) in the analyses, in whom information on self-reported PA and MRI was available at both baseline and 3-year follow-up. From the PA questionnaire, the baseline metabolic equivalent of task (MET-minute/week) and changes in MET-minute/week over three years were separately calculated for overall, leisure-time, and non-leisure time PA. WMH volume at baseline and 3-year follow-up was obtained by using an automated segmentation algorithm. RESULTS: Mixed-effect linear regression models showed that none of the baseline PA variables was associated with progression of WMH over time. People who had decreased their PA levels over three years tended to show greater progression of WMH compared with those who had maintained PA levels of ≥1200 MET-min/week (roughly equivalent to ≥300 minutes of brisk walking) in the unadjusted model (ß±SE=4.85±2.42, p=0.045); however, this association was no longer significant after adjustment for confounders (ß±SE =3.63±2.18, p=0.096). CONCLUSIONS: We did not find any significant association between PA and WMH in non-demented older adults with memory complaints. However, decrease over time in PA levels tended to be associated with progression of WMH. A larger longitudinal study with data on PA assessed using objective measures would provide important information in this field.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Bone marrow analysis of immune cells and apoptosis in patients with systemic lupus erythematosus.

OBJECTIVES: To examine the immune cell profile in the bone marrow of systemic lupus erythematosus (SLE) patients and to assess its clinical relevance. METHODS: Sixteen bone marrow samples from 14 SLE patients were compared with seven healthy control samples. The numbers of immune cells and apoptotic cells in the bone marrow were examined by immunohistochemistry. The association between immune cell subsets and clinical features was investigated. RESULTS: CD4+ T cells, macrophages and plasma cells were more common in the bone marrow of SLE patients than in healthy controls (p=0.001, p=0.004 and p<0.001, respectively). Greater numbers of CD4+ T cells and macrophages were associated with high-grade bone marrow damage. The percentage of apoptotic cells in bone marrow of SLE patients was significantly higher than that in controls (p<0.001) and was positively correlated with the number of plasmacytoid dendritic cells (p=0.013). Increased number of plasma cells along with high interleukin-6 expression was correlated with anti-double stranded DNA antibody levels and the SLE disease activity index (p=0.031 and 0.013, respectively). CONCLUSION: Bone marrow from SLE patients showed a distinct immune cell profile and increased apoptosis. This, coupled with a correlation with disease activity, suggests that the bone marrow may play a critical role in the pathogenesis of SLE.

Association study of anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms with idiopathic primary ovarian insufficiency.

STUDY QUESTION: Are the genetic polymorphisms of the anti-Müllerian hormone (AMH) and anti-Müllerian hormone type II receptor (AMHR2) genes associated with idiopathic primary ovarian insufficiency (POI) in a Korean population? SUMMARY ANSWER: The distribution of the AMH and the AMHR2 polymorphisms in a Korean POI population was not significantly different from controls. WHAT IS KNOWN ALREADY: AMH plays an important role in regulating both the primordial follicle recruitment and the cyclic selection of the antral follicles. The AMHR2 -482A>G polymorphism was associated with an earlier menopause and nulliparous women with the GG genotype had a 2.6 years earlier onset of menopause compared with the AA genotype women. Therefore, genetic variants in the AMH signal transduction pathway might affect the ovarian function of women. STUDY DESIGN, SIZE, DURATION: Case-control study. The subjects consisted of 211 idiopathic POI patients and 233 post-menopausal controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The frequency of the AMH Ile(49)Ser and AMHR2 -482A>G polymorphisms was analyzed in 211 patients with idiopathic POI and in 233 post-menopausal controls, and we also analyzed clinical characteristics, such as age at the time of POI and LH, FSH as well as estradiol levels according to the specific genotype. Genotyping for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms was performed by a minor groove binder primer/probe Taqman assay. MAIN RESULTS AND THE ROLE OF CHANCE: The genotype distributions and allele frequencies for the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were similar between the POI patients and the controls. Within POI population, the AMH Ile(49)Ser and the AMHR2 -482A>G polymorphisms were not associated with age at the time of POI and LH, FSH as well as estradiol levels. Haplotype analysis also showed no significant difference between groups. LIMITATIONS, REASONS FOR CAUTION: Study is limited to a Korean population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that genetic variants in the AMH signal transduction pathway may not influence the susceptibility of idiopathic POI. This is the first report on the association between the AMH and AMHR2 polymorphisms and idiopathic POI. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of Seoul National University Hospital Research Fund (04-2011-0870). TRIAL REGISTRATION NUMBER: N/A.

Atherogenic changes in low-density lipoprotein particle profiles were not observed in non-obese women with polycystic ovary syndrome.

STUDY QUESTION: Is a preponderance of small dense low-density lipoprotein-cholesterol (LDL-C) observed in non-obese women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Non-obese Korean women with PCOS have no quantitative or qualitative changes in LDL-C profiles. WHAT IS KNOWN ALREADY: Small dense LDL particles (sd-LDL) are more atherogenic than large buoyant ones and are strongly associated with coronary artery disease independent of other risk factors. Many investigators have found an increased proportion of atherogenic sd-LDL or a decreased mean LDL particle size in women with PCOS, but all of these studies have been based primarily on obese or overweight women with PCOS. STUDY DESIGN, SIZE, DURATION: This was a case-control study evaluating complete lipid and lipoprotein profiles in 64 PCOS patients and 64 age- and BMI-matched controls. All women with PCOS in our study population were not obese. To determine the differences in the LDL particle profiles between PCOS phenotypes, the patients with PCOS were divided into two subgroups according to the presence of clinical or biochemical hyperandrogenism. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Rotterdam criteria, we recruited 64 women (18-40 years) with PCOS who were attending a tertiary university hospital. A total of 64 premenopausal control women were matched with patients based on exact age and BMI (± 1.0 kg/m(2)). All the participants fell within the non-obese range of the BMI (<25 kg/m(2)) according to the definition of obesity for Asians. The LDL subfraction was analyzed by 3% polyacrylamide gel tube electrophoresis. Seven LDL subclasses were quantified and LDL subclasses 3-7 were small LDL subfractions. LDL subfraction scores were calculated based on the following weighted scoring system developed by the manufacturer: scores of <5.5 were categorized as phenotype A (large, buoyant LDLs), and those >5.5 were categorized as non-A phenotype (sd-LDLs). The system also determined the mean LDL particle size diameter. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the absolute level of LDL-C, mean LDL diameter or percentage of atherogenic sd-LDLs between PCOS patients and controls or between hyperandrogenic and non-hyperandrogenic PCOS subgroups. Also, none of the subjects showed a non-A LDL phenotype. The most notable finding of our study was the difference in the lipoprotein (a) levels and prevalence of its elevation in PCOS patients versus controls (P = 0.002 and P = 0.004, respectively), and between PCOS subgroups (P = 0.030 and P = 0.047, respectively). LIMITATIONS, REASONS FOR CAUTION: Inclusion of only non-obese subjects, small sample size and lack of information on other potential confounding factors, such as differences in diet and/or exercise patterns. WIDER IMPLICATIONS OF THE FINDINGS: Although our findings suggest that non-obese women with PCOS have no significant quantitative or qualitative changes in LDL-C profile, data on obese Korean women with PCOS could offer complementary findings about the possible relationship between the magnitude of obesity and LDL phenotype. Further investigations are needed to determine whether a change in lipoprotein (a) in non-obese women with PCOS is also found in other ethnic groups. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A100624). TRIAL REGISTRATION NUMBER: N/A.

Association between hormone therapy and nerve conduction study parameters in postmenopausal women.

OBJECTIVE: We aimed to analyze the association between hormone therapy (HT) and nerve conduction parameters. METHODS: This retrospective study consisted of 46 postmenopausal women not receiving HT, and 18 postmenopausal women who received HT. Eligible patients were identified from the hospital's database and the nerve conduction study was performed on the upper or lower limb without pain or other symptoms. RESULTS: No significant difference was demonstrated in the unadjusted nerve conduction parameters according to HT. After adjusting for age and body mass index, the latency of the posterior tibial motor nerve in postmenopausal women receiving HT was significantly shorter than that in women not receiving HT. Moreover, the velocity of the median motor nerve tended to be faster in postmenopausal women receiving HT than those not receiving HT, although the difference was not statistically significant. CONCLUSION: These findings imply that HT may affect the nerve conduction parameters in postmenopausal women.

Na,K-ATPase activity is required for formation of tight junctions, desmosomes, and induction of polarity in epithelial cells.

Na,K-ATPase is a key enzyme that regulates a variety of transport functions in epithelial cells. In this study, we demonstrate a role for Na,K-ATPase in the formation of tight junctions, desmosomes, and epithelial polarity with the use of the calcium switch model in Madin-Darby canine kidney cells. Inhibition of Na,K-ATPase either by ouabain or potassium depletion prevented the formation of tight junctions and desmosomes and the cells remained nonpolarized. The formation of bundled stress fibers that appeared transiently in control cells was largely inhibited in ouabain-treated or potassium-depleted cells. Failure to form stress fibers correlated with a large reduction of RhoA GTPase activity in Na,K-ATPase-inhibited cells. In cells overexpressing wild-type RhoA GTPase, Na,K-ATPase inhibition did not affect the formation of stress fibers, tight junctions, or desmosomes, and epithelial polarity developed normally, suggesting that RhoA GTPase is an essential component downstream of Na,K-ATPase-mediated regulation of these junctions. The effects of Na,K-ATPase inhibition were mimicked by treatment with the sodium ionophore gramicidin and were correlated with the increased intracellular sodium levels. Furthermore, ouabain treatment under sodium-free condition did not affect the formation of junctions and epithelial polarity, suggesting that the intracellular Na(+) homeostasis plays a crucial role in generation of the polarized phenotype of epithelial cells. These results thus demonstrate that the Na,K-ATPase activity plays an important role in regulating both the structure and function of polarized epithelial cells.

Inhibition of RhoA by p120 catenin.

RhoA organizes actin stress fibres and is necessary for cell transformation by oncogenes such as src and ras. Moreover, RhoA is implicated in cadherin clustering during the formation of adherens junctions. The catenin p120 has also been implicated in cadherin clustering through an unknown mechanism. Here we show that p120 selectively inhibits RhoA activity in vitro and in vivo. RhoA inhibition and the interaction of p120 with cadherins are mutually exclusive, suggesting a mechanism for regulating the recruitment and exchange of RhoA at nascent cell-cell contacts. By affecting RhoA activation, p120 could modulate cadherin functions, including suppression of invasion, neurite extension and junction formation.

Decreased expression of mac25 mRNA in uterine leiomyomata compared with adjacent myometrium.

PROBLEM: The pathogenesis of uterine leiomyomata is still unclear. Recently it has been suggested that mac25 plays a tumor-suppressive role in various tumors. The aims of this study were to evaluate a possible involvement of mac25 in the growth of leiomyoma and in the mechanism of a gonadotropin-releasing hormone agonist (GnRHa) inducing shrinkage of leiomyoma. METHODS OF STUDY: Mac25 mRNA transcript was measured by Northern blot in total RNA extracted from the paired specimens of leiomyoma and adjacent myometrium from untreated patients (n = 25) and from leiomyoma specimens from GnRHa-pretreated patients (n = 10). RESULTS: Mac25 mRNA expression was significantly lower in large leiomyoma (more than 150 cm3 in volume) than in adjacent myometrium and small leiomyoma (less than 120 cm3 in volume) from untreated patients. There was no difference in this expression between the proliferative and secretory phases of the menstrual cycle. Leiomyoma from GnRHa-pretreated patients had mac25 gene expression levels similar to myometrium and small leiomyoma from untreated patients. CONCLUSIONS: Mac25 may be involved in the growth of uterine leiomyoma and the action of GnRHa may, in part, be mediated by mac25.

Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases.

Pten (Phosphatase and tensin homolog deleted on chromosome 10) is a recently identified tumor suppressor gene which is deleted or mutated in a variety of primary human cancers and in three cancer predisposition syndromes [1]. Pten regulates apoptosis and cell cycle progression through its phosphatase activity on phosphatidylinositol (PI) 3,4,5-trisphosphate (PI(3,4,5)P(3)), a product of PI 3-kinase [2-5]. Pten has also been implicated in controlling cell migration [6], but the exact mechanism is not very clear. Using the isogenic Pten(+/+) and Pten(-/-) mouse fibroblast lines, here we show that Pten deficiency led to increased cell motility. Reintroducing the wild-type Pten, but not the catalytically inactive Pten C124S or lipid-phosphatase-deficient Pten G129E mutant, reduced the enhanced cell motility of Pten-deficient cells. Moreover, phosphorylation of the focal adhesion kinase p125(FAK) was not changed in Pten(-/-) cells. Instead, significant increases in the endogenous activities of Rac1 and Cdc42, two small GTPases involved in regulating the actin cytoskeleton [7], were observed in Pten(-/-) cells. Overexpression of dominant-negative mutant forms of Rac1 and Cdc42 reversed the cell migration phenotype of Pten(-/-) cells. Thus, our studies suggest that Pten negatively controls cell motility through its lipid phosphatase activity by down-regulating Rac1 and Cdc42.

De novo direct duplication of 15q15-->q24 in a newborn boy with mild manifestations.

Duplication of distal 15q results in a recognizable clinical phenotype. We report here on a 25-day-old boy with a de novo interstitial duplication of chromosome region 15q15-q24. The manifestations in this patient are milder than those of previously described patients and include minor facial anomalies, velopharyngeal insufficiency, branchial cleft cyst, and hydronephrosis. Fluorescence in situ hybridization (FISH) using a chromosome 15 painting probe confirmed that the extra material is of chromosome 15 origin. Further analysis with the SNRPN probe demonstrated that the duplication is telomeric to the Prader-Willi/Angelman syndrome critical region. This case delineates a broader spectrum for patients with duplication 15q syndrome.

The relationship among circulating insulin-like growth factor components, biochemical markers of bone turnover and bone mineral density in postmenopausal women under the age of 60.

OBJECTIVES: The changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems. DESIGN, PATIENTS AND MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N-telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31-43 and 65 postmenopausal women aged 47-60: this latter group comprised 30 normal healthy women and 35 osteoporotic women. RESULTS: Compared with premenopausal women or normal postmenopausal women, serum IGF-1 and IGFBP-3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF-II, IGFBP-1 and IGFBP-2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF-II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF-I and IGFBP-3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model. CONCLUSIONS: Circulating IGF-I and IGFBP-3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.

Microsurgical reversal of tubal sterilization: a report on 1,118 cases.

OBJECTIVE: To review and evaluate a series of patients who underwent microsurgical anastomosis of previously sterilized fallopian tubes. DESIGN: Retrospective clinical study. SETTING: Tertiary care academic center. PATIENT(S): In the 134-month span from January 1980 to February 1991, 1,118 women were evaluated for microsurgical reversal of previous tubal sterilization. MAIN OUTCOME MEASURE(S): Clinical characteristics of patients, pregnancy rates (PRs), and factors influencing the outcome. RESULT(S): Of 1,118 patients, 633 (56.6%) had been sterilized by laparoscopic cautery. Loss of children was a leading reason for requesting tubal reversal. The mean interval between tubal sterilization and reversal was 51.9 months. Nine hundred twenty-two (82.5%) patients were followed up for > 5 years. The overall PR after microsurgical tubal anastomosis was 54.8% (505 of 922) with a delivery rate of 72.5% (366 of 505), and the estimated anatomical success rate was 88.2% (814 of 922). There was no statistically significant difference in the PR or in the interval from tubal reversal to conception among the different operative procedure groups. In addition, no statistically significant difference in the PR was observed regardless of the postoperative tubal length. However, the interval from operation to pregnancy decreased significantly as the postoperative tubal length increased. The pregnant patients (n = 505) were younger and had a longer postoperative tube than the nonpregnant patients (n = 417); these differences were statistically significant. CONCLUSION(S): The pregnancy rate after microsurgical reversal of tubal sterilization was not significantly correlated with the method and duration of sterilization, the operative procedure, or the postoperative tubal length.

PIP: A retrospective analysis was conducted of the records of 1118 women who underwent microsurgical reversal of a previous tubal sterilization at Seoul (Korea) National University Hospital during 1980-91. The mean age at the time of reversal request was 31.8 years and the mean duration of sterilization was 51.9 months (range, 3-185 months). The average number of living children was 1.2. The majority (56.6%) had been sterilized by laparoscopic cautery. Major reasons for the request for reversal were loss of children (50.8%), remarriage (27.3%), and desire for sons (21.5%). Of the 992 women (82.5%) followed for more than 5 years, 505 (54.8%) achieved a total of 585 pregnancies; 366 (72.5%) of women who achieved pregnancies had a live birth. The estimated anatomical success rate was 88.2% Mean age was significantly lower in the pregnant than the nonpregnant group (30.9 versus 31.6 years), but mean duration of sterilization had no impact. The pregnancy rate was not associated with the method of tubal sterilization; however, there was a significant difference in the postoperative tubal length between pregnant and nonpregnant women (6.7 versus 6.5 cm). Despite the lack of significant correlation between the sterilization method and the success rate, Silastic Yoon's rings and Hulka clips appear to offer the greatest likelihood of tubal sterilization reversal because tissue damage is minimized.

Detection of antiendometrial antibodies in sera of patients with endometriosis by dual-colored, double-labeling immunohistochemical method and western blot.

PROBLEM: This study was undertaken to determine whether specific binding activities against endometrial proteins in sera of patients with endometriosis are detectable and, if so, to identify endometrial antigens involved in autoimmunity in endometriosis. METHOD: Sera from 33 patients with endometriosis and 20 cord sera (controls) were tested against endometria of patients and their protein extracts by dual-colored, double-labeling immunohistochemical method, and Western blotting. RESULTS: Antiendometrial binding activities were detected in sera of 2 (10.0%) control patients and 13 (48.2%) patients with endometriosis by the immunohistochemical method. Endogenous immunoglobulin G (IgG) binding to endometrial proteins had molecular weights (MW) of 26, 28, 54, 85, 107 and 116 kDa. Most sera of both control and patients showed reactivity against endometrial proteins with MW of 34, 36, 56 and 77 kDa. However, there were specific IgG autoantibodies reactive against the endometrial proteins of 71, 92, and 103 kDa in sera of 55.2% (16/29) of patients but not in the control sera. Over 80% (10/12) of patients' sera with binding activities detectable by the immunohistochemical method also tested positive by Western blot analysis. CONCLUSIONS: These data show that specific IgG antibodies reactive against endometrial antigens are detectable in sera from some patients with endometriosis.

The efficacy of a combination administration of gonadotropin-releasing hormone agonist and gonadotropins for controlled ovarian hyperstimulation in IVF program.

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation (COH) due to poor follicular growth or premature LH surge, the efficacy of pituitary suppression with gonadotropin-releasing hormone agonist (GnRHa) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of leuprolide acetate (Lupron) and FSH/hMG or pure FSH from May to December, 1989. After suppression phase, serum E2 and progesterone levels decreased significantly, but there was no change in serum LH and FSH levels. There was no occurrence of premature LH surge during COH. Eleven cycles (9.8%) were cancelled, and 3 cycles (3.0%) failed in the transvaginal oocytes retrieval. The 7.00 +/- 3.32 follicles (FD greater than or equal to 12 mm) were observed, and 6.11 +/- 4.15 oocytes were retrieved. The 3.59 +/- 2.57 oocytes were fertilized and cleaved with the cleavage rate of 55.7%. In 83 IVF patients, 4.08 +/- 2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83 +/- 3.31 oocytes were available for transfer. When compared with the previous 108 cycles, the cancellation rate during COH was decreased and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRHa therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

Oocyte donation program using a simplified hormonal regimen.

It has been well recognized that both the synchronization of luteinizing hormone (LH) surge between the donor and the recipient for normally cycling women and the complex steroid replacement regimen given on a sequential and incremental basis for women with primary or secondary ovarian failure are two important aspects in oocyte donation. In oocyte donation program at SNUH, a simplified hormonal regimen applicable both to normally cycling women and to those with ovarian failure which consisted of administering 2 mg estradiol (E2) valerate orally 3 times a day augmented with 100 mg progesterone (P) in oil intramuscularly daily starting on the day preceding the oocyte retrieval from the donor was utilized. From July 1988 to December 1989 at SNUH, 11 cycles of oocyte donation program in 10 infertile patients were undertaken and 5 patients succeeded in pregnancy.