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).
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Endometriosis (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 (E
) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties.
We performed a retrospective study of 209 EM cases and 115 women without EM.
Pain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E
) and estrone (E
), 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.
Of the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E
(2OH-3MeO-E
). Higher 2OH-3MeO-E
was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34);
=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E
and 2OH-E
levels (
< 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E
levels (OR=1.86; 95%CI 1.06-3.27;
=0.032).
The 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes.
Endometriosis is an estrogen-dependent inflammatory disease affecting women in their reproductive age. Due to non-specific symptoms, women with endometriosis are often misdiagnosed or are accurately ...diagnosed only after several years. Diagnosis of peritoneal endometriosis is especially challenging and relies only on laparoscopic surgery. To date, different molecules have been proposed as potential non-invasive biomarkers of endometriosis; however, none have been confirmed as clinically useful. Therefore, this study aimed to discover novel plasma biomarker candidates for peritoneal endometriosis using an antibody array platform. This study included patients with endometriosis-like symptoms characterized by the absence (controls) or presence of peritoneal endometriosis (cases) after laparoscopic surgery and histological evaluation. Patients were further divided into secretory and proliferative groups, according to the phase of their menstrual cycle. Their plasma samples were collected and analyzed on an antibody array platform targeting more than 1350 proteins with over 1820 antibodies. In the proliferative group, the analysis revealed three differential proteins between cases and controls: ITB3, ITA2B2, and ACVL-1. In the secretory group, none of the examined proteins reached the log-fold change (logFC) and significance thresholds simultaneously. The potential of the identified differential proteins as plasma biomarker candidates for peritoneal endometriosis should be evaluated on a larger cohort, and their role in endometriosis should be investigated in further studies.
Background: Uterine leiomyomas are the most common benign uterine tumours in women. They are symptomatic in 20 to 50 % of cases. Symptoms associated with leiomyomas include heavy, prolonged menstrual ...bleeding leading to anaemia, dysmenorrhoea, pelvic pressure and pain, impaired function of adjacent organs, such as bladder and bowel, and reproduction dysfunction. Options for medical therapy are currently limited to preoperative reduction of symptoms related to uterine bleeding and fibroid size. Recently, selective progesterone receptor modulators (SPRM) have been introduced and approved in preoperative treatment of leiomyomas. The aim of our study was to assess the efficacy of preoperative treatment with SPRM ulipristal acetate (UPA) on leiomyoma shrinkage and haemoglobin (Hb) concentration improvement. Methods: Fifty patients with symptomatic leiomyomas were assigned for preoperative treatment with 5 mg of UPA daily for 12 weeks. Before and a week after the UPA treatment was completed, leiomyoma volume was measured, and Hb concentrations and the amount of uterine bleeding were assessed. The outcomes were changes from baseline in leiomyoma volume and the proportion of patients with controlled bleeding after the treatment. Results: After the completion of UPA treatment there was a mean volume reduction of the largest myoma by 33.3 %, whereas the mean volume reduction of up to 3 largest myomas was 32.3 %. Volume reduction was in both cases statistically significant. During the treatment course 41 (82.0 %) women were amenorrhoeic and the other 9 (18.0 %) had a significant reduction in uterine bleeding. The reduction in bleeding was accompanied by improvement in Hb levels in all patients. Conclusion: Preoperative treatment with UPA for 12 weeks effectively reduces leiomyoma volume and facilitates or even makes laparoscopic surgery feasible. It is also beneficial for correcting anaemia, which is of outmost importance for postoperative recovery.
Introduction: Nowadays, endometriosis represents the most frequent cause of female infertility.The treatment of choice is by all means laparoscopic surgery, which results in more than a 60 % ...pregnancy rate, regardless of the stage of the disease. For the rest of patients in vitro fertilization (IVF) is the most appropriate treatment of choice. Views of the impact of endometriosis on IVF outcome remain controversial and subject to debate. Whereas some studies have documented that endometriosis is associated with reduced pregnancy rates, others failed to prove this association. The present study was designed to elucidate whether or not endometriosis affects IVF outcome at our institution. The study was retrospective, statistical significance was considered at p ≤ 0.05. Methods: In 96 patients (group A) that underwent IVF program the only cause of infertility was endometriosis which had been previously treated surgically. Sixty-two (64.6 %) patients had minimal or mild endometriosis (group C) and 34 (35.4 %) had moderate or severe stage of the disease (group D). The control group (group B) consisted of 305 patients who underwent IVF procedure for tubal or idiopathic infertility. Among other variables, pregnancy rate per cycle and per embryo transfer (ET), take-home-baby rate (THBR) per cycle and per ET were compared between the study and control groups of patients as well as between both groups with endometriosis. The study was retrospective. Statistical significance was defined as p ≤ 0.05. Results: No statistically significant differences were found in any of the compared parameters. In Group "A" pregnancy rate per cycle and per ET was 41.7 % and 46.8 % respectively, compared to Group "B" where it was 36.4 % and 40.5 % respectively. THBR per cycle and per ET in Group "A" was 35.4 % and 43.0 %, whereas in the control group it was 30.5 % and 33.9 % respectively. Pregnancy rate per cycle and per ET in Group "C" was 40.3 % and 48.1 % whereas in Group "D" it was 44.1 % and 55.6 % respectively. THBR per cycle and per ET in Group "C" was 33.9 % and 40.4 % whereas in Group "D" it was 38.2 % and 48.1 % respectively. Conclusions: Endometriosis does not affect the outcome of IVF procedures. We believe that appropriate surgical technique is of paramount importance in patients with endometriosis, leading to favourable IVF outcomes.
Endometriosis is a common gynaecological condition characterized by severe pelvic pain and/or infertility. The combination of nonspecific symptoms and invasive laparoscopic diagnostics have prompted ...researchers to evaluate potential biomarkers that would enable a non-invasive diagnosis of endometriosis. Endometriosis is an inflammatory disease thus different cytokines represent potential diagnostic biomarkers. As panels of biomarkers are expected to enable better separation between patients and controls we evaluated 40 different cytokines in plasma samples of 210 patients (116 patients with endometriosis; 94 controls) from two medical centres (Slovenian, Austrian). Results of the univariate statistical analysis showed no differences in concentrations of the measured cytokines between patients and controls, confirmed by principal component analysis showing no clear separation amongst these two groups. In order to validate the hypothesis of a more profound (non-linear) differentiating dependency between features, machine learning methods were used. We trained four common machine learning algorithms (decision tree, linear model, k-nearest neighbour, random forest) on data from plasma levels of proteins and patients' clinical data. The constructed models, however, did not separate patients with endometriosis from the controls with sufficient sensitivity and specificity. This study thus indicates that plasma levels of the selected cytokines have limited potential for diagnosis of endometriosis.
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.
There have been some proposals that stem cells exist in the ovarian surface epithelium (OSE) of the adult human ovary; however, no direct evidence of such cells has been given until now. The aim of ...this study was to isolate the putative ovarian stem cells (OSCs) from the OSE layer in women with no naturally present oocytes and follicles—20 postmenopausal women and five women with premature ovarian failure. Small round cells with a bubble-like structure and diameters from 2 to 4 μm were isolated from the material obtained by OSE scraping. They expressed early embryonic developmental markers such as stage-specific embryonic antigen-4 and Oct-4, Nanog, Sox-2, and c-kit transcription markers, and they displayed prominent c-kit immunohistochemical staining. These cells were separated by density gradient centrifugation and grown
in vitro, where they proliferated. Some of them grew intensively and reached a diameter of approximately 20 μm after 5–7 days. In the OSE cell culture, oocyte-like cells developed, which reached a diameter of up to 95 μm and expressed Oct-4A, Oct-4B, c-kit, VASA, and ZP2 transcription markers, corresponding to early oocytes. They did not express SCP3 meiotic marker. In conclusion, the discovered cells are proposed to represent the adult OSCs with the expression of embryonic stem cell markers. The expression of germ lineage marker c-kit points toward their primordial germ cell ancestry. A new term “embryonic-like stem cells of the adult” is proposed for embryonic-like stem cells that might persist in various tissues and organs of adults. These findings could be used for further studies aimed at the autologous treatment of ovarian infertility and degenerative diseases.
To determine the proportion and the characteristics of patients who did or did not respond after 3 months of ulipristal acetate (UPA) therapy.
In this retrospective cohort study conducted in the ...University Hospital of Bordeaux (France) and University Medical Center Ljubljana (Slovenia), symptomatic non-menopausal patients with fibroids that qualified for surgery were pretreated by 3 months of oral UPA 5 mg/day. Clinical success was defined by normalization of the bleeding score, and/or regression of pelvic pain, and/or abdominal distension. Imaging success was defined by reduction in fibroid volume ≥ 25%.
The clinical and imaging success rates were 54/66 (82%) and 39/66 (59%) respectively. The absence of previous pregnancy (p = 0.004) and the size of the dominant fibroid ≥ 80 mm (p = 0.004) were independent factors associated with clinical failure. Age <35 years (p = 0.02) was the only independent factor associated with imaging failure.
Young women developing fibroids and/or women with large fibroids may be resistant to ulipristal acetate therapy.
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