Biomedical subjects

Aydin Arici

Publications and source records attributed to Aydin Arici.

At least 19 recordsLinked to original sources

PubMed2007

A comparison between follitropin alpha filled by mass and follitropin alpha filled by bioassay in the same egg donors.

This study assessed the ovarian stimulation characteristics of recombinant follitropin alpha filled by mass (rFSH-fbm) versus recombinant follitropin alpha filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose) and the second one with rFSH-fbm (Gonal-f RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin alpha filled by mass as opposed to follitropin alpha filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.

Adult↗

PubMed2006

Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx.

OBJECTIVE: To determine whether women with hydrosalpinx would have diminished endometrial HOXA10 expression and whether salpingectomy would reverse HOXA10 suppression. The homeobox gene HOXA10 is a transcription factor that is necessary for embryo implantation; its expression in human endometrium correlates with receptivity and implantation. Increased endometrial HOXA10 expression may be one mechanism by which salpingectomy results in increased implantation rates in IVF. DESIGN: Prospective clinical trial. SETTING: Academic medical center. PATIENT(S): Women with unilateral or bilateral hydrosalpinx. INTERVENTION(S): Expression of HOXA10 was examined prospectively during the midluteal phase in endometrium obtained from infertile women (n = 9) with hydrosalpinges before and after salpingectomy, as well as from fertile controls (n = 6). Quantitative HOXA10 mRNA expression was determined by real-time reverse-transcription polymerase chain reaction, and HOXA10 protein expression was determined by immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of HOXA10 mRNA and protein. RESULT(S): Expression of HOXA10 mRNA was significantly lower in infertile women with hydrosalpinges, compared with the case of fertile controls. Salpingectomy resulted in a statistically significant, 15-fold increase in endometrial HOXA10 expression. Immunohistochemical analysis confirmed the quantitative real-time reverse-transcription polymerase chain reaction findings. Increased HOXA10 expression was evident in both glandular epithelial cells and endometrial stroma. CONCLUSION(S): HOXA10 is necessary for implantation. Here, we demonstrate decreased HOXA10 expression in response to hydrosalpinx fluid as a potential molecular mechanism for diminished implantation rates. Salpingectomy restores endometrial HOXA10 expression. This may be one mechanism by which salpingectomy results in augmented implantation rates in IVF.

Adult↗

PubMed2006

Role of gonadotropin-releasing hormone antagonists in poor responders.

OBJECTIVE: To evaluate the role of GnRH antagonists in poor-responder protocols. DESIGN: Literature review. CONCLUSION(S): The optimum stimulation protocol for poor responders is unknown. Although many IVF programs currently use GnRH antagonists for poor responders, there have been only four prospective, randomized trials comparing GnRH antagonists to alternate protocols. None of these studies had sufficient power to evaluate a difference in pregnancy rates (PRs), and in all four cases, IVF outcomes were comparable. Nevertheless, interest in the use of GnRH antagonists in poor responders has continued. GnRH antagonists may be associated with simpler stimulation protocols, lower gonadotropin requirements, reduced patient costs, and shorter downtimes between consecutive cycles. However, the greatest advantage of GnRH antagonists may lie in the ability to assess ovarian reserves immediately prior to deciding whether or not to initiate gonadotropin stimulation. The ability to respond to cycle-to-cycle variation in antral follicle counts may allow the optimization of oocyte yield and reduce cycle cancellation rates. It remains to be seen if this approach (initiating gonadotropins only in cycles where an adequate antral follicle count is present) also translates into higher clinical PRs for poor responders.

Clinical Trials as Topic↗

PubMed2006

Estradiol increases apoptosis in human coronary artery endothelial cells by up-regulating Fas and Fas ligand expression.

CONTEXT: In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified. OBJECTIVE: We hypothesized that 17beta-estradiol (E2) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): The effect of E2 on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated. RESULTS: HCAECs in culture treated with E2 showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E2 treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E2 treatments. CONCLUSIONS: E2 increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E2 suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these cells.

Apoptosis↗

PubMed2006

The role of endometrium in endometriosis.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Several theories have been proposed to explain the pathogenesis of this disease. According to Sampson's retrograde menstruation theory, endometrial cells are refluxed through the fallopian tubes during the menstruation and implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very common phenomenon among women of reproductive age, there must be other factors that may contribute to the pathophysiology and/or pathogenesis of endometriosis. Genetic predisposition, environmental factors, and alterations in immune and endocrine functions are believed to play significant roles in the establishment and maintenance of endometriosis. Although the eutopic endometriums of women with and without endometriosis are histologically similar, studies revealed that there are many fundamental differences between these two tissues. Invasive properties, decreased apoptosis, alterations in expression of specific gene and proteins, and increased steroid and cytokine production have been identified in eutopic endometrium of women with endometriosis. Furthermore, significant biochemical differences exist even between ectopic and autologous eutopic endometrium. These differences can be explained by the direct effects of an inflammatory peritoneal environment.

Cell Adhesion↗

PubMed2006

Regulation of FAS ligand expression by chemokine ligand 2 in human endometrial cells.

Human endometrium is a dynamic tissue under the influence of numerous hormones, growth factors, and cytokines interacting to maintain a balance of cellular growth, differentiation, and apoptosis. We have previously demonstrated that several factors including interleukin-8, extracellular matrix, and steroid hormones modulate FASLG, one of the apoptotic molecules, in human endometrium. Chemokine ligand 2 (CCL2), a monocyte chemoattractant and activating factor, is a cytokine involved in endometrial function. CCL2 is elevated in the peritoneal fluid of women with endometriosis. We hypothesize that increased levels of CCL2 in the endometriotic environment may upregulate FASLG expression in human endometrial stromal cells and induce a local immunotolerance in endometriosis. To test our hypothesis, we studied the in vitro regulation of FASLG expression and apoptosis by CCL2 in endometrial stromal cells. Western blot analysis revealed that CCL2 upregulated FASLG protein expression in cultured endometrial stromal cells. Based on semiquantitative RT-PCR analysis, CCL2 did not alter either FAS or FASLG mRNA expression in endometrial stromal cells. Immunocytochemistry results from the same cells treated with CCL2 demonstrated upregulation of FASLG protein expression. CCL2 did not change rate of apoptosis in endometrial stromal cells as evaluated by TUNEL assay. However, an increased apoptotic rate was detected in Jurkat (T lymphocytes) cells cocultured with endometrial stromal cells previously treated with CCL2. We speculate that increased FASLG expression by CCL2 may induce apoptosis of T lymphocytes and thus produce an immunotolerant environment for the development of ectopic implants.

Adult↗

PubMed2006

Statins inhibit growth of human endometrial stromal cells independently of cholesterol availability.

Endometriosis is characterized by ectopic growth of endometrial tissues. Statins, inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been shown to decrease proliferation of several mesenchymal tissues. Actions of statins may be related to decreased availability of cholesterol as well as intermediate metabolites of the mevalonate pathway downstream of HMGCR. This study was designed to evaluate effects of statins on growth of endometrial stromal cells and to investigate mechanisms of these effects. Human endometrial stromal cells were cultured in the absence and in the presence of serum and with or without mevastatin and simvastatin. DNA synthesis and viable cell numbers were determined. Effects of statins were also evaluated in the presence of mevalonate and squalene. Furthermore, effects on phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1) (also known as extracellular signal-regulated kinase [ERK1/2]) were determined. Mevastatin and simvastatin induced a concentration-dependent inhibition of DNA synthesis and viable cell count in chemically defined media and in the presence of serum. Mevalonate, but not squalene, abrogated inhibitory effects of statins on cell proliferation. Statins inhibited MAPK3/1 phosphorylation. This is the first study demonstrating that statins inhibit growth of endometrial stromal cells. This effect is also demonstrable in the presence of a supply of cholesterol and may be related to decreased activation of MAPK3/1. The present observations may be relevant to potential therapeutic use of statins in conditions such as endometriosis.

Cell Proliferation↗

PubMed2006

Endometriosis associated with Stage IA clear cell ovarian carcinoma in a woman with IVF-ET treatments in the Yale Series.

A 42-year-old woman with Stage IA, grade 3 clear cell ovarian carcinoma arising within an endometrioma after multiple ovarian stimulation attempts was a unique case from a total of 900 patients who underwent laparoscopy for infertility and pelvic pain between 1996 and 2002 at Yale University. Her previous treatments included two laparoscopic cystectomies for left ovarian endometriomas and four cycles of IVF-ET that resulted in one miscarriage and two successful pregnancies. Although it has been suggested that controlled ovarian hyperstimulation may predispose to the development of ovarian cancer, more recent studies postulate a protective effect if fertility treatments ultimately result in successful pregnancy. Our unusual case serves as a reminder that clear cell adenocarcinoma may coexist with endometriosis, and that parity does not necessarily protect infertility patients against the development of ovarian cancer.

Adenocarcinoma, Clear Cell↗

PubMed2006

Estrogen-mediated regulation of p38 mitogen-activated protein kinase in human endometrium.

CONTEXT: Estrogen predominantly exerts its biological effects through the genomic pathway by binding to its intracellular receptors, interacting with the estrogen response element located in the promoter region of the target gene, and thus regulating gene transcription. There has been an increasing body of evidence regarding nongenomic actions of estrogen. Estrogen activates multiple signaling cascades, including the MAPK pathway. p38 MAPK plays key roles in mediating apoptosis, proliferation, and inflammation, which all take place in the endometrium during cyclical changes under the influence of estrogen. OBJECTIVE: We hypothesized that estrogen might activate the p38 MAPK pathway in endometrial cells and exert some of its actions through this pathway in the endometrium. INTERVENTIONS: p38 MAPK phosphorylation was analyzed using in vivo and in vitro techniques. RESULTS: Total and phosphorylated p38 MAPK immunostainings were more intense in epithelial cells compared with stromal cells, and the phosphorylated/total p38 MAPK ratio was significantly higher in the functional endometrial layer compared with the basal layer (P < 0.05). Estradiol significantly increased p38 MAPK phosphorylation in endometrial stromal cells in culture within 2 min (P < 0.05), and this phosphorylation was blocked by a specific p38 MAPK inhibitor. Moreover, tamoxifen and raloxifene also increased phosphorylation of p38 MAPK. The estrogen receptor antagonist ICI 182,780 reversed the estrogen-induced p38 MAPK phosphorylation in endometrial stromal and epithelial cells, suggesting involvement of the estrogen receptor. CONCLUSION: Our results indicate the involvement of estrogen in regulating p38 MAPK activity in endometrial cells, suggesting a nongenomic action of estrogen through this MAPK in the endometrium.

Adult↗

PubMed2006

Expression of interleukin-8 receptors in patients with adenomyosis.

OBJECTIVE: To investigate the expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 in adenomyosis. DESIGN: Comparative immunohistochemical study. SETTING: Academic medical center. PATIENT(S): Thirty women who had undergone hysterectomy and were proved histopathologically to have adenomyosis, and 27 women without adenomyosis who had a hysterectomy for nonendometrial pathology such as leiomyomata or benign ovarian cysts. INTERVENTION(S): Tissue sections were immunostained with murine monoclonal anti-human CXCR1 and CXCR2 antibodies. MAIN OUTCOME MEASURE(S): Microscopic evaluation to assess the presence and localization of CXCR1 and CXCR2 throughout the menstrual cycle in both eutopic endometrial and adenomyotic tissues of women with adenomyosis and compare it with normal endometrium. RESULT(S): In eutopic endometrium of women with adenomyosis, proliferative phase samples showed higher epithelial CXCR1 and CXCR2 staining intensity compared with proliferative phase samples of normal endometrium. Adenomyosis foci expressed higher epithelial CXCR1 compared with the homologous eutopic endometrium and normal endometrium. On the other hand, adenomyosis foci and the homologous eutopic endometrium showed similar epithelial CXCR2 staining intensity, and this expression was higher than the normal controls. CONCLUSION(S): Intrinsic abnormalities concerning IL-8 and its receptor system may be present in the eutopic endometrium of women affected by adenomyosis. These findings suggest that IL-8 receptors may be involved in the pathogenesis and/or pathophysiology of adenomyosis.

Adult↗

PubMed2006

Sequential embryo assessment outperforms investigator-driven morphological assessment at selecting a good quality blastocyst.

Two selection methods (morphology-only and a sequential embryo assessment algorithm) were compared within the same IVF clinic to determine which method best identifies the embryos on day 3 that will develop into the highest quality on day 5. The sequential embryo assessment algorithm was significantly better at selecting the best embryo and selecting a blastocyst compared with the morphology-only method.

Adult↗

PubMed2006

p16, retinoblastoma (pRb), and cyclin D1 protein expression in human endometriotic and adenomyotic lesions.

OBJECTIVE: To investigate the expression of p16, retinoblastoma (pRb), and cyclin D1 oncoproteins in endometriomas and adenomyosis. DESIGN: Immunohistochemical study for p16, pRb, and cyclin D1 proteins in formalin-fixed paraffin-embedded endometriotic and adenomyotic tissues. SETTING: University hospital. PATIENT(S): Tissues from 25 women with endometriomas and 31 women with adenomyosis were evaluated. INTERVENTION(S): Tissue samples were collected during gynecologic surgery and confirmed by histology to have endometriosis or adenomyosis. Nuclear expression of p16, pRb, and cyclin D1 proteins was examined by immunohistochemistry. MAIN OUTCOME MEASURE(S): Distribution and intensity of immunostaining. RESULT(S): In the proliferative phase of the cycle, p16 was detected in 77% of adenomyosis tissues but in only 15% of endometriosis tissues. Moreover, in adenomyosis samples positive for p16, 100% of the adenomyotic cells expressed p16, whereas only 10%-20% of endometriosis cells from positive cases expressed p16. In contrast, pRb was detected in 28% of endometriosis cases but not in any adenomyotic tissues. Cyclin D1 was absent in both endometriotic and adenomyotic tissue samples. CONCLUSION(S): Differences in oncoprotein expression between endometriotic and adenomyotic tissues provide further evidence that the pathogenesis of endometriosis is different from that of adenomyosis.

Adenovirus E1A Proteins↗

PubMed2006

Cellular biology of myomas: interaction of sex steroids with cytokines and growth factors.

Many investigators who have been trying to delineate the pathophysiology of leiomyomata believe in the autocrine-paracrine model of tumor growth,where ovarian hormones act as regulators of gene expression in cells. These affected cells overproduce the stimulatory and fibrogenic cytokines and growth factors to which they respond, resulting in sustained, self-stimulated proliferation and fibrogenesis. A number of cytokines and growth factors have been investigated in leiomyomata to determine which cytokines or factors may be responsible for mediating the growth-promoting effects of ovarian hormones. A review of the literature reveals that TGF-3 is the only growth factor shown to be overexpressed in leiomyomata versus myometrium, hormonally regulated both in vivo and in vitro, and both mitogenic and fibrogenic in these tissues. The authors believe that, given the extent and depth of the current research on the cellular biology of leiomyoma, the cellular mechanisms responsible in the pathogenesis of leiomyoma will be identified clearly within the foreseeable future. This will enable researchers to develop therapy directed against the molecules and mechanisms at the cellular level, which undoubtedly will have a major impact on the number of hysterectomies being performed for a"fibroid uterus."

Cytokines↗

PubMed2006

Myomas and assisted reproductive technologies: when and how to act?

The effect of myomas on reproductive outcome has been the subject of many studies; however, a definitive answer is still missing. Therefore, the authors have tried to outline some guidelines for the management of women who have uterine myomas and desire to conceive. The location and size of the myomas are the two parameters that influence the success of a future pregnancy. Subserosal myomas seem to have little, if any,effect on reproductive outcome, especially if they are up to 5 to 7 cm in diameter. Intramural myomas that do not encroach upon the endometrium also can be considered to be relatively harmless to reproduction, if they are smaller than 4 to 5 cm in diameter. This is the ambiguous gray zone of the subject, and where research should be focused before a consensus can be established. Myomas that compress the uterine cavity with an intramural portion (submucous myoma type II) and submucous myomas significantly reduce pregnancy rates, and should be removed before assisted reproductive techniques are used. Hysteroscopic myomectomy is the gold standard for the treatment of submucous myomas. For other myomas, abdominal myomectomy, or laparoscopic myomectomy--when the experience of the surgeon and the facilities are sufficient--are the best alternatives. In most of the literature, the pregnancy rates were increased and the miscarriage rates were decreased after surgery with these two techniques. Other alternative treatment modalities, such as CUV, laparoscopic myolysis, or MRI-guided focused ultrasound, are to be monitored and evaluated thoroughly before they are applied as routine procedures.

Clinical Trials as Topic↗

PubMed2006

Options for medical treatment of myomas.

It is evident that complex biochemical interactions are involved in the regulation of myoma growth, and ovarian steroid hormones have significant influence on this process. Current myoma therapies manipulate the hormonal environment to achieve myoma regression and control of bleeding. Although several of these therapies achieve some level of success, further studies are necessary to evaluate the current and long-term effects of these therapies. In clinical medicine each patient must be evaluated thoroughly, and the decision for medical therapy or surgery--and for which medical therapy--needs to be individualized. If one medical therapy does not work, several other effective therapies are available.

Clinical Trials as Topic↗

PubMed2006

Impact of duration and dose of gonadotrophins on IVF outcomes.

In order to examine whether the duration of the follicular phase and changes in daily gonadotrophin dosages impact IVF outcome, a retrospective analysis of women who underwent oocyte retrieval and fresh embryo transfer was performed. Among the parameters assessed were the number of days of gonadotrophin stimulation, changes in the daily dosage of gonadotrophins, total ampoules of gonadotrophins, embryo implantation rates, clinical pregnancy rates and ongoing pregnancy rates. The number of days of gonadotrophin stimulation, as determined by standard follicular size criteria did not appear to influence IVF outcomes. There was no significant difference in pregnancy rates between women who were stimulated for <9 days, 10-11 days or >12 days. When grouped by amount of starting daily dose of gonadotrophins there was a significant inverse relationship between gonadotrophin requirements and pregnancy rates (P=0.02). The data suggest that the success of an IVF cycle depends on the ovaries' ability to develop follicles of the appropriate size, not the speed at which the ovaries perform this function.

Adult↗

PubMed2006

Anatomic factors in recurrent pregnancy loss.

Anatomic uterine defects are present in 15% of women evaluated for three or more consecutive spontaneous abortions. These anatomic abnormalities can be classified as congenital or acquired. In addition to pregnancy loss, uterine malformations appear to predispose women to other reproductive difficulties including infertility, preterm labor, and abnormal presentation. These poor reproductive outcomes resulting from uterine septum, intrauterine adhesions, polyps, and fibroids are amenable to surgical correction. Therefore, it is essential to make an accurate diagnosis to offer an adequate treatment. In this article, we review the common congenital and acquired uterine anomalies associated with recurrent pregnancy losses, and discuss contemporary diagnosis and treatment options.

Abortion, Habitual↗

PubMed2006

Endometrial cancer and fertility.

PURPOSE OF REVIEW: Endometrial cancer can affect reproductive-age women who may desire fertility preservation. This article discusses the current, available data about conservative management of endometrial cancer in young women. RECENT FINDINGS: Reproductive-age women with well differentiated endometrial carcinoma have an overall favorable prognosis provided that the tumor is identified at an early, noninvasive stage; however, advanced disease can be present. This article discusses current modalities to evaluate and clinically stage endometrial cancer including hysteroscopy, dilation and curettage, pelvic ultrasound, abdominopelvic computed tomography scan, pelvic magnetic resonance imaging, tumor marker CA125 level, and surgical exploration with laparoscopy or laparotomy. Thorough evaluation is critical as 10 to 29% of young women with endometrial cancer have a synchronous ovarian malignancy. Detailed counseling about the risks and benefits of conservative management, and expectations for fertility after treatment, surveillance, and definitive surgical management is essential. Multiple effective protocols exist for conservative treatment of endometrial cancer, and the initial response rates are as high as 57 to 75%. Successful pregnancies have occurred after conservative management, spontaneously, and with assisted reproductive technologies. SUMMARY: There are no standard recommendations for selection of appropriate women, treatment protocols, or long-term surveillance for conservative management of clinical stage I endometrial adenocarcinoma, and larger prospective clinical studies are warranted.

Adenocarcinoma↗