Predoperacijsko zdravljenje miomov z ulipristal acetatom

Izhodišče: Miomi so najpogostejši benigni tumorji maternice. Približno petina do polovica žensk z miomi ima simptome oz. pri njih miomi hitro rastejo. Najpogosteje gre za podaljšane in/ali močne menstruacijske krvavitve, ki povzroče anemijo, dismenorejo, bolečine zaradi pritiska na sosednje organe, redkeje pa neplodnost in motnje pri odvajanju urina in blata. Zdravljenje miomov je potrebno pri bolnicah s simptomi in v primeru, ko gre za hitro rastoče miome. Selektivni modulatorji progesteronskih receptorjev (SMPR) so novejša zdravila za predoperacijsko zdravljenje miomov, ki le-te učinkovito zmanjšajo, povzročijo amenorejo ali zmanjšanje krvavitev, s tem pa izboljšajo krvno sliko. Namen raziskave je bil ugotoviti vpliv predoperacijskega zdravljenja s SMPR ulipristal acetatom (UPA) na velikost miomov in krvno sliko. Metode: Petdesetim (50) bolnicam s simptomatskimi miomi smo pred načrtovanim kirurškim posegom predpisali SMPR UPA 5 mg za dvanajst tednov. Pred in po končanem zdravljenju smo izmerili velikost miomov, ocenili količino krvavitve iz maternice in preverili krvno sliko. Rezultati: Po končanem zdravljenju z UPA se je povprečna prostornina največjega mioma zmanjšala za 33,3 %, skupna povprečna prostornina do 3 največjih miomov pa za 32,3 %. Zmanjšanje prostornine je bilo v obeh primerih statistično značilno. Amenoroičnih je bilo 41 (82,0 %) bolnic, pri 9 (18,0 %) pa so se menstruacijske krvavitve znatno zmanjšale. Pri vseh bolnicah smo opazili porast koncentracije hemoglobina. Zaključek: 12-tedensko predoperacijsko zdravljenje z UPA učinkovito zmanjša velikost miomov in s tem olajša oziroma omogoči najsodobnejše laparoskopsko kirurško zdravljenje. Ker povzroči amenorejo oziroma zmanjša količino menstruacijske krvavitve, se izboljša tudi krvna slika, kar je pomembno za okrevanje po operaciji

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

ObjectivesEndometriosis (EM) is an estrogen-dominant inflammatory disease linked to infertility that affects women of reproductive age. EM lesions respond to hormonal signals that regulate uterine tissue growth and trigger inflammation and pain. The objective of this study was to evaluate whether estradiol (E2) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties.DesignWe performed a retrospective study of 209 EM cases and 115 women without EM.MethodsPain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E2) and estrone (E1), their 2-, 4- and 16- hydroxylated (OH) and methylated (MeO) derivatives (n=16) were measured by mass spectrometry. We evaluated the associations between estrogen levels and EM anatomic sites, surgical stage, risk of EM, and symptoms reported by women. Spearman correlations established the relationships between circulating steroids.ResultsOf the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E1 (2OH-3MeO-E1). Higher 2OH-3MeO-E1 was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34); P=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1 levels (P< 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E1 levels (OR=1.86; 95%CI 1.06-3.27; P=0.032).ConclusionsThe 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes

Exogenous Ether Lipids Predominantly Target Mitochondria

Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking

In vitro maturation of oocytes from excised ovarian tissue in a patient with autoimmune ovarian insufficiency possibly associated with Epstein-Barr virus infection

Abstract Background Some reports show that it is possible to isolate immature oocytes from human ovarian tissue retrieved by a cortex biopsy or ovariectomy of non-stimulated ovaries and mature them in vitro. The mature oocytes can be vitrified and stored for in vitro fertilization, which, along with ovarian tissue cryopreservation, is mostly practiced in young cancer patients to preserve their fertility. There is much less data on this new approach in women with a natural ovarian insufficiency, which can be caused by different factors, including viral infection. In this case report this advanced methodology was used in a young patient suffering from ovarian insufficiency which was possibly associated with Epstein-Barr virus and infectious mononucleosis (glandular fever). Methods This case report included a 27-year-old patient who attended our infertility clinic because of ovarian failure as a part of autoimmune polyendocrinopathy that occurred after Epstein-Barr virus infection, which has rarely been reported until now. Although antral follicles were observed in her ovaries by ultrasound monitoring, she was amenorrhoeic with menopausal concentrations of follicle-stimulating hormone (FSH) and without mature follicles. Therefore, a small biopsy of ovarian cortex tissue was performed using laparoscopy to retrieve immature oocytes. The retrieved oocytes were matured in vitro, cryopreserved, and stored for in vitro fertilization and potential pregnancy. Results Four immature, germinal vesicle (GV) oocytes were found and removed from tissue, denuded mechanically by a pipette, and matured in vitro in a maturation medium with added FSH and hCG as well as in co-culture with cumulus cells, which were retrieved by their denudation. Three oocytes matured in vitro to the metaphase II (MII) stage and were vitrified for in vitro fertilization along with ovarian tissue cryopreservation. Conclusion Our results show that Epstein-Barr infection is possibly associated with autoimmune ovarian failure. The devastating impact on fertility in such disorder can be successfully avoided by in vitro maturation of oocytes from excised ovarian tissue

The frequency of endometriosis among healthy and infertile women

Izhodišča: Endometrioza je pojav tkiva s histološkimi in funkcionalnimi značilnostmi endometrija zunaj maternične votline. Pogostnost endometrioze pri ženskah v rodni dobi brez simptomov in znakov bolezni ostaja še vedno neznana. Obolenje je verjetno najpogostejši vzrok neplodnosti oziroma zmanjšane plodnosti. Namen: V raziskavi smo želeli ugotoviti pogostnost endometrioze v populaciji zdravih žensk in opredeliti endometriozo kot pomemben vzrok neplodnosti. Metode: Raziskava je potekala retrospektivno. Preiskovanke smo razdelili v dve skupini. V prvi skupini je bilo 378 zdravih brezsimptomatskih žensk, ki so želele laparoskopsko sterilizacijo, v drugi skupini je bilo 111 primarno in sekundarno neplodnih žensk, ki jim je bila z namenom odkrivanja vzroka neplodnosti opravljena diagnostična laparoskopja. Iz osebnih popisov preiskovank smo dobili anamnestične in laparoskopske podatke o pogostnosti in stadiju endometrioze, kliničnih simptomih in starosti preiskovank. Dobljene podatke smo primerjali med zdravimi in neplodnimi ter med primarno in sekundarno neplodnimi preiskovankami. Statistično značilno razliko smo ovrednotili pri p [je manjši ali enak] 0,05. Rezultati: Pogostnost endometrioze v populaciji neplodnih žensk (33 %) je bila značilno višja (p=0,01) kot v populaciji zdravih žensk (3,7 %). V obeh skupinah je bila najpogosteje ugotovljena minimalna endometrioza (57 in 86 %). Med skupinama primarno in sekundarno neplodnih žensk razlika v pogostnosti endometrioze ni bila statistično značilna. Endometrioza je predstavljala najpogosteje odkrito patologijo (33 %) v skupini neplodnih preiskovank. Zaključki: Endometrioza je prisotna pri relativno veliko zdravih in je najpogosteje odkrita patologija pri neplodnih ženskah.Background: Endometriosis involves an appearance of endometriotic tissue with all of its histological and functional properties outside the uterine cavity. The frequency of endometriosis in women of reproductive age without symptoms and signs of disease remains unknown. This disease is probably the most frequent cause of infertility and impaired fertility. Objective: The objective of our study was to estimate the frequency of endometriosis in a population of healthy women and to define endometriosis as an important cause of infertility. Patients and methods: The study was carried out retrospectively. The women were divided into 2 groups. In the first group, there were 378 healthy asymptomatic women who wanted laparoscopic sterilization. In the other one, there were 111 primarily and secondarily infertile women, on whom diagnostic laparoscopy was performed in order to discover the cause of their infertility. From medical records of all the patients, medical history and laparoscopic data were gathered about the frequency and status of endometriosis, clinical symptoms and age. These data were compared between healthy and infertile women and between primarily and secondarily infertile women. The statistically significant difference was evaluated at p [is less or equal] 0.05. Results: The frequency of endometriosis in the group of infertile women (33 %) was significantly higher (p=0.001) than in the group of healthy women (3.7 %). In most cases, minimal endometriosis was found in both groups (57 % vs. 86 %). The difference in the frequency of endometriosis between the groups of primarily and secondarily infertile women was not statistically significant. Endometriosis represented the most frequently found pathology (33 %) in the group of infertile women. Conclusions: Endometriosis is present in a relatively high number women and is also the most commonly found pathology among infertile women

THE OUTCOME OF LAPAROSCOPIC TREATMENT OF ENDOMETRIOSISASSOCIATED INFERTILITY

Background. Many studies have shown significant reduction of fertility in endometriosis. Mechanisms of infertility are still not completely clear. The aim of our study is to obtain the effectiveness of laparoscopic treatment of infertility for different stages of endometriosis. Methods. The effectiveness of laparoscopic treatment of infertility in endometriosis was observed through a questionnaire that was sent to 281 patients (pts), who had laparoscopic treatment at the Department of Obstetrics and Gynecology Ljubljana during the period from 1999 to 2006 due to endometriosis as the only cause of infertility. 53.4 % (150/281) pts, who answered the questionnaire, were divided into group I (minimal and mild endometriosis) and group II (moderate and severe endometriosis). We established the rate of pregnancy (in total, spontaneous and ART) and compared the results between two groups. Relatively small percentage of answered questionnaires was most likely due to the fact that the questionnaires were sent to pts who were operated several years ago and did not respond or have changed their address. Because the study is still ongoing, we present partial results. Results. For 132 pts wanting to get pregnant the overall pregnancy rate was 76.5 % (101/132). The rate of pregnant pts depended on the stage of endometriosis. In group I 86.8 % (79/91) pts became pregnant – 58. 2 % (46/79) spontaneously, 41.8 % (33/79) with ART. In group II 53.6 % (22/41) pts became pregnant – 68.2 % (15/22) spontaneously, 31.8 % (7/22) with ART. The difference between groups was statistically significant (p < 0.05). Conclusions. Our results are comparable to the results found in the literature. Laparoscopic treatment of infertility is effective in all four stages of endometriosis. According to our results laparoscopic treatment has the primary role in the treatment of endometriosis-associated infertilit

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium Cultured In Vitro in the Presence of Follicular Fluid

The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure

Isolation of Small SSEA-4-Positive Putative Stem Cells from the Ovarian Surface Epithelium of Adult Human Ovaries by Two Different Methods

The adult ovarian surface epithelium has already been proposed as a source of stem cells and germinal cells in the literature, therefore it has been termed the “germinal epithelium”. At present more studies have confirmed the presence of stem cells expressing markers of pluripotency in adult mammalian ovaries, including humans. The aim of this study was to isolate a population of stem cells, based on the expression of pluripotency-related stage-specific embryonic antigen-4 (SSEA-4) from adult human ovarian surface epithelium by two different methods: magnetic-activated cell sorting and fluorescence-activated cell sorting. Both methods made it possible to isolate a similar, relatively homogenous population of small, SSEA-4-positive cells with diameters of up to 4 μm from the suspension of cells retrieved by brushing of the ovarian cortex biopsies in reproductive-age and postmenopausal women and in women with premature ovarian failure. The immunocytochemistry and genetic analyses revealed that these small cells—putative stem cells—expressed some primordial germ cell and pluripotency-related markers and might be related to the in vitro development of oocyte-like cells expressing some oocyte-specific transcription factors in the presence of donated follicular fluid with substances important for oocyte growth and development. The stemness of these cells needs to be further researched