29 results on '"Tomaž Tomaževič"'
Search Results
2. EFFECT OF MORPHOLOGY AND BLASTOCYST DEVELOPMENT ON THE OUTCOME OF SINGLE-BLASTOCYST TRANSFER IN THE IN VITRO FERTILIZATION PROGRAMME
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Brigita Valentinčič Gruden, Irma Virant Klun, Lili Bačer Kermavner, Jerneja Kmecl, Jožica Mivšek, Tomaž Tomaževič, and Eda Vrtačnik Bokal
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blastocista ,elektivni prenos enega zarodka ,morfologija ,razvitost blastociste ,nosečnost ,Medicine - Abstract
Background. Multiple pregnancy can be prevented by an elective single blastocyst transfer. The aim of this prospective study was to evaluate the effect of blastocyst development and morphology on the outcome of single blastocyst transfer. Methods. In this study 157 women with single blastocyst transfer were included; their mean age was 33.6 years, range 20–42. Embryos were cultured to the blastocyst stage and evaluated using the Gardner’s classification. An elective single blastocyst transfer was performed in 83 women although 2 or more blastocysts developed (Group 1) and in 74 with only one developed blastocyst (Group 2). Results. In Group 1 (2 or more blastocysts) the pregnancy rate was a significantly higher than in Group 2 (1 blastocyst only) (39.8 % vs. 23.0 %; P < 0.05). After the transfer of a single expanded blastocyst no statistical difference in the pregnancy rate between the two groups was observed (45.5 % vs. 44.6 %). A significantly higher pregnancy rate was found after the transfer of one expanded blastocyst with a good embryoblast and trophoblast morphology compared to the transfer of a single early blastocyst (45.6 % vs. 7.1 %, P < 0.05). Conclusions. After single blastocyst transfer, the likelihood of achieving a pregnancy is higher in women with 2 or more blastocysts developed. And also the likelihood of achieving a pregnancy is higher with an expanded blastocyst transferred with good embryoblast and trophoblast morphology. The blastocyst development is the main predictor of pregnancy, which may reflect the embryonic genetic status.
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- 2018
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3. NEW CLASSIFICATION OF SPERM MORPHOLOGY BEFORE ICSI AT MAGNIFICATION OF X6000
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Katja Knez, Irma Virant Klun, Branko Zorn, Tomaž Tomaževič, and Eda Vrtačnik Bokal
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IMSI ,morfologija spermijev ,spermij I. in II. razreda ,vakuola ,Medicine - Abstract
Background. At conventional ICSI, sperm to be injected into the oocyte is chosen at magnification of 400 times which does not permit abnormalities of fine sperm structures to be seen. By using a new method, intracytoplasmic morphologically selected injection (IMSI), motile sperm with a normal head, base and no vacuoles present in the head can be selected at magnification of 6000 times. Vacuoles in the sperm head reflect the damage of nucleus and/or DNA (fragmented or single-stranded DNA). Spermatozoa with vacuoles in the head have lower fertilization capacity and lead to abnormal embryo development, unsuccessful implantation, or spontaneous abortion. Methods. The aim of this study was to evaluate the percentage of men with abnormal sperm morphology (teratozoospermia) included in the ICSI programme, in which it is possible to find a morphologically normal sperm without vacuoles in the head using IMSI method. In each selected sperm we evaluated the morphology of head (normal = 2 points), base (normal = 1 point) and presence of vacuoles in the head (one small or no vacuoles = 3 points). Totally normal sperm (or with one small vacuole in the head) was allotted 6 points. According to this evaluation, sperm were divided into three classes: class I (6–4 points), class II (3–1 points) and class III (0 points). Sperm of class I and II were suitable for injection into the oocyte, whereas sperm of class III were not. Results. Before ICSI, the prepared semen of 13 patients which had teratozoospermia (alone or in combination with other semen abnormalities) was evaluated by the IMSI method. Sperm of class I was found in 5 men (38 %), and sperm of class II in the remaining men (62 %). Sperm of class III was found in all men. On average, 0.7 sperm of class I and 6.1 sperm of class II per man with teratozoospermia were found. Conclusions. Morphologically normal sperm without vacuoles in the head can be found in less than half of men undergoing the ICSI programme. Further research will show, whether it is possible to improve the clinical results of the ICSI method by the sperm selection with the IMSI method.
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- 2018
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4. USE OF HYALURONAN-RICH TRANSFER MEDIUM FOR A SINGLE BLASTOCYST TRANSFER IN VITRO FERTILIZATION PROCEDURE
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Sara Korošec, Irma Virant Klun, Tomaž Tomaževič, and Helena Meden Vrtovec
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blastocista ,hialuronan ,implantacija ,zunajtelesna oploditev ,Medicine - Abstract
Background. The best way to avoid undesirable multiple pregnancies following in vitro fertilization procedure (IVF) is to perform elective single embryo transfer, but the procedure might result in a reduction of the pregnancy rates. Aim of our study was to establish whether a single blastocyst transfer using a hyaluronan rich transfer medium results in higher pregnancy rates in comparison to the transfer using a conventional transfer medium. Material and methods. Our prospective randomized study included 107 patients enrolled in the 1st, 2nd and 3rd classical IVF or intracytoplasmic sperm injection (ICSI) treatment attempt. Patients included were under 37 years of age with at least one blastocyst developed in the procedure. In the study group (47 patients) blastocyst transfers using the hyaluronan rich transfer medium were performed and in the control group (60 patients) the conventional medium was used. The pregnancy rates in the study and in the control group were compared. Results. The average pregnancy rate per single blastocyst transfer was 30 %; there were no twin pregnancies. The single blastocyst transfer using hyaluronan resulted in a non-significantly higher pregnancy rate (11 %). A significantly higher pregnancy rate with the use of hyaluronan was found in the subgroup of patients with two or more blastocysts developed in their 2nd and 3rd IVF attempt (p = 0.045). Conslusions. The single blastocyst transfer results in high implantation rates. Hyaluronan significantly contributes to higher implantation rates in a selected subgroup of patients following previous implantation failure and with multiple blastocysts developed.
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- 2018
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5. SPERM SELECTION WITH HYALURONAN AND BLASTOCYST DEVELOPMENT AFTER ICSI
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Lili Bačer Kermavner, Irma Virant Klun, Eda Vrtačnik Bokal, Tomaž Tomaževič, and Helena Meden Vrtovec
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selekcija semenčic ,blastocista ,vnos semenčice v citoplazmo jajčne celice ,hialuronan ,oploditev ,Medicine - Abstract
Background. Selection of mature sperm for intracytoplasmic sperm injection (ICSI) has recently been made possible by hyaluronan, a naturally occurring substance found in the cumulus cells. Only fully mature sperm have the receptors on the head that effectively bind to the oocyte cumulus, or, to be more precise, to hyaluronan. The aim of this study was to evaluate the differences in fertilization rates and in embryo development to the blastocyst stage after ICSI performed either with sperm selected by hyaluronan or by standard morphological sperm appearance. Methods. This retrospective study involved 17 couples undergoing ICSI. One half of sibling oocytes were fertilized with sperm selected by hyaluronan (84 oocytes), and the other half with sperm selected on the basis of morphological appearance (89 oocytes). The comparison between the two groups involved fertilization rates and the percentages of arrested embryos, and delayed (morulae) and advanced blastocysts. Blastocysts were classified as early, developed and expanded. Results. In the group with hyaluronan-selected sperm 65 % of oocytes fertilized, and in the group with sperm selected by morphological appearance 70 % of oocytes. The fertilization rates did not statistically differ between the two groups, and neither did the percentages of arrested embryos (47 % vs. 62 %), morulae (11 % vs. 11 %), and blastocysts (42 % vs. 26 %). In the group with hyaluronan-selected sperm the shares of expanded and early blastocysts were significantly greater (P ≤ 0.04 and P ≤ 0.002, respectively) than in the group with sperm selected according to morphological appearance. Conclusions. The use of hyaluronan for sperm selection in ICSI does not affect fertilization rates. Hyaluronan-selected sperm improves subsequent development of embryos. A larger study sample is required for the assessment of hyaluronan-selected sperm on the achievement of pregnancies.
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- 2018
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6. ELECTRON MICROSCOPE COMPARISON OF ENDOMETRIUM FROM UTERINE SEPTUM AND ENDOMETRIUM FROM THE LATERAL WALL
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Helena Ban Frangež and Tomaž Tomaževič
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pregrada maternice ,biopsija endometrija ,ugnezditev ,Medicine - Abstract
Background. Septate uterus is an important risk factor for spontaneous abortion and preterm delivery. The role of septate uterus in infertility is still questionable. The mechanism of the adverse effects of a septate uterus is not yet understood. The basic theory proposes that the septum represents a less suitable environment for a developing embryo when compared to the unaffected uterine wall. The aim of our study was to compare the endometrial surface morphology in women with septate uterus. Material and methods. This prospective observational study includes endometrial biopsies that were taken from women with uterine septum. We have included 30 consecutive women who came for the hysteroscopic resection of the septum. The operation was scheduled at the time of the implantation window; an endometrial biopsy was performed and samples were taken from the septum and from the lateral wall and compared under electron microscope. Pinopode development stage and the number of endometrial glands were the main outcome measures. Results. Comparison of the endometrium from the septum with that of the lateral wall showed no difference in the number of endometrial glands (2.0 endometrial glands seen at 250 × magnification vs. 2.5; ns ), not even in the pinopode stage (17.7 day vs. 18.1 day, ns). Conclusions. To our knowledge, there are three researches that have compared endometrium from the septum to the endometrium from the lateral wall in infertile women and all have differences in observed parameters. Our results cannot support earlier findings. The question of mechanism, how septum influences on pregnancy should be further investigated in the larger sample.
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- 2018
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7. THE ART PROGRAMME IN SLOVENIA – OUR PLACE IN EUROPE (SLOVENIA IN EIM 2005 YEAR REPORT)
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Tomaž Tomaževič, Irma Virant-Klun, Veljko Vlaisavljevič, Borut Kovačič, Primož Reš, Žan Reš, and Helena Meden-Vrtovec
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IVF ,ICSI ,FER ,EIM ,multiple pregnancy ,Medicine - Abstract
Background: We have been sending Slovenian data on biomedically assisted procreation (BMAP) to European IVF Monitoring (EIM) registry since 2001. In order to see our place in Europe, we compare our data for 2005 to the last available EIM – 2005 report data. Methods: The summaries of all three Slovenian centres sent to EIM 2005 report : 3292 BMAP cycles (730 IVF cycles, 1495 ICSI cycles, 584 FER cycles, 470 IUI cycles) in a population of 2.003 358 inhabitants were compared to the results in 418 111 BMAP cycles reported from differ- ent European countries. Results: The calculated cumulative live birth rate per fresh IVF /ICSI cycle in Slovenia was 27.7 % . The availability in Slovenia corresponded to 1.643 assisted reproduction cycles and 1402 IVF, ICSI or FER cycles per million inhabitants .The percentage of infants born after BMAP was 3.9 % . In 2005 there were 0.4 % births of triplets and 18.9 % births of twins. Conclusions: The results in 2005 reflect our law which permits the fertilisation of all oocytes and the cryopreservation of vital remaining embryos The calculated cumulative live birth rate per fresh IVF /ICSI cycle was comparable to the best rated European countries. Considering the availability of BMAP per million inhabitants, Slovenia was on the 7th place in Europe. The percentage of infants born after BMAP was the highest in Europe . Slovenia was between 12 European countries with a successful PGD programme to prevent severe hereditary diseases.
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- 2018
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8. THE OUTCOME OF LAPAROSCOPIC TREATMENT OF ENDOMETRIOSISASSOCIATED INFERTILITY
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Vesna Šalamun, Martina Ribič Pucelj, Tomaž Tomaževič, Andrej Vogler, and Eda Vrtačnik Bokal
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endometrioza ,neplodnost ,laparoskopsko zdravljenje ,Medicine - Abstract
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 infertility
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- 2018
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9. Ovarian surface epithelium stem cells: oogenesis in vitro?
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Irma Virant-Klun, Primož Rožman, Branko Cvjetičanin, Andrej Vogler, Polona Klemenc, Elvira Maličev, Alojz Ihan, Jasna Šinkovec, Eda Vrtačnik-Bokal, Tomaž Tomaževič, and Helena Meden-Vrtovec
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embryonic stem cells ,in vitro culture ,oocyte ,ovarian surface epithelium ,Medicine - Abstract
Background: The dogma that the total number of follicles and oocytes available for reproduction are determined at birth, and that one follicle and one oocyte are recruited from the existing pool to mature in each menstrual cycle still persists. There is an increasing experimental evidence that this might not be true. In the ovarian surface epithelium there might be nondifferentiated stem cells that might differentiate into oocytes also in adult life. In this research we aimed at isolating putative stem cells from the ovarian surface epithelium and at evaluating in vitro oogenesis in the ovarian cell culture in vitro in women without naturally present follicles and oocytes in their ovarian cortex – postmenopausal women and women with premature ovarian failure.Methods: Ovarian surface epithelium was scraped from the ovaries of 20 postmenopausal women and 5 women with premature ovarian failure. We tried to find putative stem cells in ovarian scraping and to confirm them by transcription markers Oct-4, Sox-2, and Nanog, and by surface antigen SSEA-4. Cell culture was set up by scraped cells in DMEM/F-12 medium with phenol red, which shows a weak estrogenic activity. Ovarian cell culture was cultured for 20 days in a CO2-incubator at 37 °C and 5 % CO2. Development of cells in the culture was followed and the presence of oocyte-like cells was evaluated by using different methods – evaluation of morphology, transcription markers, surface antigen markers, oocyte immunohistochemical markers, and flow cytometry after propidium iodide staining.Results: In all postmenopausal women and in 4 out of the 5 women with premature ovarian failure putative stem cells were isolated from the ovarian surface epithelium, which were positive for transcription markers of embryonic stem cells Oct-4, Sox-2, Nanog, and for surface antigen SSEA-4. In all these women ovarian cell culture was successfully established. In all cultures oocyte-like cells developed approximately on day 5 of culture, which were positive for transcription marker Oct-4 and immunohistological germ cell markers c-kit, Oct-4, ZP2, DAZL, and even meiotic marker SCP3. Marker SCP3 was expressed in oocyte-like cells developed in ovarian cell culture of postmenopausal women, but not in patients with premature ovarian failure. Flow cytometry after propidium iodide staining revealed a population of potentially haploid oocyte like cells in postmenopausal women. Stem cells developed also into some somatic cell types, including fibroblasts, neuron-, and mioblast-like cells. In patients with premature ovarian failure oocyte-like cells were developed only at the presence of autologous patient’s serum and mostly at the presence of heterologous follicular fluid serum, whereas they did not develop at the presence of fetal calf serum.Conclusions: First results are promising as they indicate the new insight into the physiology of the adult human ovary. In the ovarian surface epithelium putative stem cells with embryonic character are present, which can develop into the oocyte-like cells and other types of cells in vitro. Further research is required to understand better these new findings.
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- 2007
10. Assisted reproduction technology procedures using donated gametes at the department of obstetrics and gynecology, University medical centre Ljubljana
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Bojana Pinter, Tomaž Tomaževič, Helena Meden-Vrtovec, Sašo Drobnič, Liljana Bačer-Kermavner, Irma Virant-Klun, Mojca Kolbezen-Simoniti, Alenka Hribernik, Sara Korošec, Ksenija Geršak, and Blanka Gradišek
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infertility ,in vitro fertilization ,sperm donation ,oocyte donation ,donor procedures ,Medicine - Abstract
Background: After the law on assisted reproductive technologies (ART) in Slovenia was legalized, donor procedures at the Department of Ob/Gyn, University Medical Center Ljubljana, were started at the end of 2001; by September 2005 221 recipient couples have applied for the procedures: 153 couples for donor semen (DS) procedures and 68 couples for donor oocyte (DO) procedures.Methods: Gametes can be donated by healthy men aged 18–55 years and healthy women aged 18 to 35 years. After donation, donor semen is frozen, and donor oocytes are fertilized with the semen of the recipient, after which embryos are frozen. If after a 6-month safety period repeated tests on sexually transmitted infections are negative, thawed semen or embryos can be used for the recipients.Results: Gametes have been donated by 97 men and 30 women. ART using DS was performed in 98 couples. Pregnancy rate per embryo transfer (ET) of fresh embryos has been 30 %; pregnancy rate per ET of thawed embryos has been 20 %. ART using DO have been performed in 46 couples. After a 6-months safety period, embryos of 38 couples have been transferred to recipients. Pregnancy rate on ET of thawed embryos has been 19 %.Conclusions: Our experiences have shown, that gamete donation program can be implemented also in Slovenia and that donor procedures are equally successful as homologous procedures. In the future we intend to consolidate the program.
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- 2006
11. HYSTEROSCOPIC RESECTION OF UTERINE SEPTUM – EFFECTS ON PREGNANCY
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Helena Ban, Tomaž Tomaževič, Martina Ribič Pucelj, Andrej Vogler, and Eda Bokal Vrtačnik
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uterine septum ,pregnancy ,preterm delivery ,Medicine - Abstract
Background. In women with spontaneous abortions, preterm deliveries or infertility, septate uterus is often detected on transvaginal ultrasound examination. Since 1993 we have used hysteroscopic resection to correct this anomaly. The aim of this study was to evaluate the effect of the arcuate uterus on the course of pregnancy and its outcome, and the effect of hysteroscopic resection of the arcuate uterus on the prognosis of pregnancy.Patients and methods. Retrospectively we analyzed prospectively collected data. Between 15 February 1993 and 31 December 1999 we performed 760 hysteroscopic resections of the septum at the Department of Obstetrics and Gynecology in Ljubljana. We evaluated the course of pregnancy and its outcome only, therefore we enrolled 241 women, who conceived spontaneously before and after operation.Results. In the group of women with arcuate uterus (n = 111) there were 244 pregnancies before hysteroscopic resection: 38 (15.6%) ended with a delivery and 202 (82.8%) with a spontaneous abortion. In the group of women with septate uterus (n = 130) there were 269 pregnancies: 42 deliveries (15.6%) and 224 (83.3%) spontaneous abortions. After hysteroscopic resection there were 109 pregnancies in the women with arcuate uterus: 91 (83.5%) deliveries and 16 (14.7%) spontaneous abortions; in the septate uterus group there were 118 pregnancies: 98 (83.2%) deliveries and 16 (13.5%) spontaneous abortions. In both groups there was a significant improvement in the delivery rate (p < 0.00000). Before resection the preterm delivery rates were significantly higher in both groups (arcuate: 50.0%; septate: 35.1%) than after the resection (arcuate: 11.3%; septate 17.7%).Conclusions. The women with either septate or arcuate uterus are at a higher risk for spontaneous abortion and preterm delivery. Hysteroscopic resection significantly decreases the risk in both groups of women.
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- 2003
12. SALPINGOSCOPY – A USEFUL TOOL IN THE DIAGNOSIS OF PATHOLOGICAL CHANGES IN THE TUBE
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Irma Virant and Tomaž Tomaževič
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salpingoscopy ,tubal pregnancy ,tubal infertility ,Medicine - Abstract
Background. To confirm the hypothesis that the incidence of pathological changes of the mucosa in the contralateral tube is higher in women with tubal pregnancy than in fertile women. To evaluate a new method for direct assessment of the tubal mucosa, salpingoscopy.Patients and methods. In the prospective study we enrolled 58 women in the period June 1998–April 2001. The study group consisted of 23 women with tubal pregnancy and 19 infertile women seeking diagnostic laparoscopy. The exclusion criteria was tubal pregnancy that occurred in spite of an inserted intrauterine device or after an in vitro fertilizationembryo transfer (IVF-ET). The control group consisted of 16 fertile women. Laparoscopy was performed in all the enrolled women. Peritubal adhesions were diagnosed laparoscopically, whereas intratubal adhesions were diagnosed by salpingoscopic examination of the ampullary tubal mucosa.Results. Laparoscopy revealed peritubal adhesions in 31 women: in 43% of women with a history of ectopic pregnancy, in 94% of infertile women, and in 19% of fertile women. On salpingoscopy pathologic changes of the ampullary tubal mucosa were most frequent in infertile women (47.7%), less frequent in women with a history of ectopic pregnancy (26.1%), and the least frequent in fertile women (6.3%). Pearson correlation coefficient yielded a weak correlation between the extensiveness of laparoscopically assessed lesions and salpingoscopically assessed pathology. None of the 13 women with pathologic changes of the ampullary tubal mucosa conceived spontaneously, whereas 43.5% of women with healthy tubal mucosa on salpingoscopy conceived spontaneously. The women with diagnosed pathologic changes of the tubal mucosa were referred for IVF treatment to prevent further ectopic pregnancies.Conclusions. Salpingoscopy is a useful method in the evaluations tubal functions. Salpingoscopy is beneficial to the women with pathological changes of the tube: by referring them for IVF-ET further tubal pregnancies are avoided. The results of endoscopic tubal surgery can be further improved through a proper selection of patients by salpingoscopy.
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- 2003
13. SURGICAL TREATMENT OF POLYCYSTIC OVARIES IN INFERTILE PATIENTS
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Martina Ribič Pucelj, Tomaž Tomaževič, Andrej Vogler, Eda Vrtačnik Bokal, Sašo Drobnič, Branko Zorn, and Helena Meden Vrtovec
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polycystic ovaries ,infertility ,surgical treatment ,Medicine - Abstract
Background. Polycystic ovaries (PCO) are manifested either independently or as a syndrome (PCOS). They are one of the commonest endocrinopathy in women of reproductive age. Despite a variable clinical picture one of the leading symptoms is infertility for anovulation. Surgical treatment of the disease witnessed a revival after the introduction of minimally invasive operative laparoscopy. Various techniques of ovarian tissue destruction have been applied, the most common being laparoscopic electrocoagulation of the ovaries (LECO). The aim of this retrospective study was to assess the pregnancy rates and pregnancy outcomes following LECO.Patients and methods. From 1993 and 2000 inclusive LECO was performed at the Reproductive Unit, Department of Obstetrics and Gynecology Ljubljana in 222 infertile patients with PCO(S), in whom previous medical ovulation induction failed or in whom overreaction of the ovaries to gonadotropin treatment occurred. To the questionnaire, mailed to the patients, 185 (83.3%) responded. The evaluation of the outcome of LECO treatment involved 157 patients, since the patients who underwent in vitro fertilization (IVF-ET) treatment for other causes of infertility prior to LECO, were exclude from the analysis. LECO was performed under general endotracheal anesthesia using a 3-puncture technique. On each ovary 5– 15 (mean 10) punctures were made with a monopolar electric needle, energy of 300 W, and duration of 4 seconds. Statistical analysis was done using Chi-square test and odds ratios.Results. After LECO 99 (63.3%) of the 157 patients conceived, 56 (54.6%) spontaneously and 43 (45.4%) after additional postoperative ovarian stimulation. Pregnancy was registered in 58 (59.0%) patients with primary, and in 41 (41%) patients with secondary infertility, in 20 (57%) patients with PCO, 79 (65%) with PCOS, in 71 (64.1%) patients with a normal partner’s spermiogram, and in 28 (46.1%) patients with the partner’s oligoasthenoteratospermia of the 1st or 2nd degree. The differences were not statistically significant. Pregnancy ended with delivery in 87 (88.1%) patients, and in spontaneous abortion in 11 (11%); 1 (0.9%) pregnancy was ectopic. Singletons were born to 82 (82.9%) and twins to 5 (5.2%) patients, the latter to the patients receiving ovarian stimulation immediately after surgery. In the patients, enrolled in IVF-ET treatment for a failed hormonal and/or surgical treatment, the delivery rate per ET was 23.4% (19/48) in those with a previous LECO, and 12.9% (36/115) in those without a previous LECO (p < 0.05). No surgical complications were registered.Conclusions. LECO is an efficient treatment of infertility in patients with PCO(S). It results in high pregnancy and low spontaneous abortion rates, and reduces the risk of ovarian hyperstimulation syndrome following gonadotropin treatment.
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- 2003
14. MULTIPLE PREGNANCY IN THE TWENTY YEARS OF IVF/ET IN SLOVENIA
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Tomaž Tomaževič, Irma Virant Klun, Brigita Valentinčič Gruden, Helena Meden Vrtovec, Veljko Vlaisavljević, Borut Kovačič, Primož Reš, and Ivan Verdenik
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multiple pregnancy ,IVF/ICSI ,elective transfer of 2 blastocysts ,Medicine - Abstract
Background. Slovene data on iatrogenic multiple pregnancy after IVF/ICSI procedures are presented. The influence of elective transfer of two high-quality embryos on the incidence of iatrogenic multiple pregnancy were evaluated.Methods. Retrospective analysis of the Slovene IVF/ICSI data in the period 1983–2000.Results. In 17436 IVF/ICSI cycles 3068 pregnancies were achieved. Of the 2308 deliveries 369 (16%) were twins and 49 (2%) triplets. Of the 2827 newborns 738 (26%) were twins and 148 (5%) triplets. With elective transfer of two high quality embryos in 1999 and 2000 in two of the three Slovene centres for assisted reproduction, the pregnancy rate per transfer increased (32%), triplet deliveries decreased to 2/492 deliveries (0.4%) (p < 0.000), and twin deliveries remained unchanged 111/492 deliveries (23%).Conclusions. After elective transfer of two high-quality embryos and cryopreservation of surplus high-quality embryos in two of the three Slovene centres in the years 1999 and 2000, the problem of iatrogenic triple and higher rate multiple pregnancies has been successfully resolved, but the twin delivery rate still remains too high. Only by elective transfer of a single high-quality embryo the high multiple pregnancy rate after IVF/ICSI procedures could be avoided.
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- 2003
15. POSSIBLILTIES FOR A SINGLE EMBRYO TRANSFER IN AN IN VITRO FERTILIZATION PROGRAMME
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Irma Virant Klun, Tomaž Tomaževič, Branko Zorn, Lili Bačer Kermavner, Brigita Valentinčič Gruden, Jerneja Kmecl, Martina Ribič Pucelj, Andrej Vogler, Eda Bokal Vrtačnik, Sašo Drobnič, Bojana Pinter, Jožica Mivšek, and Helena Meden Vrtovec
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in vitro fertilization ,blastocyst ,transfer ,freezing ,thawing ,pregnancy ,Medicine - Abstract
Background. Since in in vitro fertilization two embryos – blastocysts are routinely transferred, the twin pregnancy rates are higher than in the general population. The aim of our study was to evaluate the clinical results after elective single-blastocyst transfer.Methods. Retrospectively we analysed clinical results of 696 in vitro fertilization cycles. The cycles were divided into 37 cycles, in which an elective single blastocyst transfer was performed (group 1), and in 659 cycles, in which an elective double blastocyst transfer was performed (group 2). The pregnancy rates, twin pregnancy rates, and spontaneous abortion rates were compared between the two groups. Additionally we evaluated the effect of the method of in vitro fertilization (classical IVF and ICSI) and female age (< 38 years and > 38 years) on the clinical results after a single or double blastocyst transfer.Results. After an elective single or double blastocyst transfer, there was no statistically significant difference in pregnancy rates (30% vs. 46%); after a single blastocyst transfer there were no twin pregnancies, whereas after a double blastocyst transfer the pregnancy rate was 18%. After a double blastocyst transfer, the method of in vitro fertilization did not affect the twin pregnancy rate, whereas in women younger than 38 years, the twin pregnancy rate was significantly higher than in women aged > 38 years (19% vs. 6%; p < 0,05).Conclusions. Clinical results obtained after an elective single and double blastocyst transfer are comparable. By the transfer of one blastocyst twin pregnancies are avoided. Elective single blastocyst transfer is recommended in women, younger than 38 years.
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- 2003
16. SURGICAL TREATMENT OF ENDOMETRIOSIS IN INFERTILE PATIENTS
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Andrej Vogler, Martina Ribič Pucelj, and Tomaž Tomaževič
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endometriosis ,infertility ,surgical treatment ,outcome ,Medicine - Abstract
Background. Endometriosis is nowadays probably the most frequent cause of infertility or subfertility and is revealed in approximately 30–40% of infertile women. The association between fertility and minimal or mild endometriosis remains unclear and controversial. Moderate and severe forms of the disease distort anatomical relations in the minor pelvis, resulting in infertility. The goals of endometriosis treatment are relief of pain symptoms, prevention of the disease progression and fertility improvement. Treatment of stages I and II endometriosis (according to the R-AFS classification) may be expectative, medical or surgical. In severely forms of the disease (stage III and IV) the method of choice is surgical treatment. Combined medical and surgical treatment is justified only in cases, in which the complete endometriotic tissue removal is not possible or recurrence of pain symptoms occur. Nowadays, laparoscopic surgical treatment is the golden standard being the diagnostic and therapeutic tool during the same procedure. The aim of this study was to evaluate the fertility rate after surgical treatment of different stages of endometriosis.Patients and methods. In prospectively designed study 100 infertile women were included. The only known cause of infertility was endometriosis. In group A there were 51 patients with stage I and II endometriosis, whereas in group B there were 49 patients with stage III and IV of the disease. Endometriosis was diagnosed and treated laparoscopically. Endometriotic implants were removed either with bipolar coagulation or CO2 laser vaporisation, whereas adhesions were sharp or blunt dissected, and endometriomas stripped out of ovaries. Pregnancy rates were calculated for both groups of patients, and statistically compared between the groups.Results. Mean age of patients was 29.25 (SD ± 4.08) years and did not significantly differ between the groups of patients (29.5 years in group A and 29 years in group B). In group A 31 (60.8%) out of the 51 patients conceived spontaneously within 24 months after surgery. In group B 30 (61.2%) out of the 49 patients conceived spontaneously after surgery. The difference in pregnancy rates between the groups was not statistically significant.Conclusions. Surgical treatment of endometriosis in infertile patients is by all means effective and most appropriate, although some have not confirmed its value in patients with minimal or mild endometriosis comparing it with the no-treatment protocol. The limitations of this study should be considered. The main drawback is its design: the trial was not a randomised controlled one. We advocate that endometriosis once diagnosed must be surgically treated, to prevent progression of the disease at least. Endometriosis appears to progress in two-thirds of patients within a year from the diagnosis, and it is impossible to predict, in which patients it will progress. It would be unethical, and even unprofessional not to remove even the smallest endometriotic implants when the disease is confirmed by laparoscopy.
- Published
- 2003
17. ARE THE TWINS, BORN AFTER AN IVF-ET PROCEDURE ANY DIFFERENT THAN TWINS, BORN AFTER SPONTANEOUS CONCEPTION?
- Author
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Sara Korošec, Tomaž Tomaževič, Ivan Verdenik, Vinko Boc, Tanja Premru Sršen, Irma Virant Klun, Brigita Valentinčič Gruden, and Tanja Talan
- Subjects
IVE-ET ,pregnancy ,birth ,twins ,Medicine - Abstract
Background. Multiple pregnancy is in itself already a risk factor for the course and outcome of the pregnancy and birth. Its frequency in in-vitro fertilisation is approximately twenty fold in comparison to natural conception which is also why it is one of the main problem areas of pregnancy and birth after an IVF-ET procedure. The aim of our research is to determine whether the twins, born after an IVF-ET procedure are any different than twins, born after spontaneous conception.Methods. The research was retrospective in nature. It included 1511 twin pregnancy patients who gave birth to twins between April 1987 and May 1995 and between January 1997 and December 1999. Our research group consisted of 255 mothers and 510 twins, born after an IVF-ET procedure. The research was divided into a cohort and controlled study. In the cohort study the research group was compared to the entire Ljubljana cohort of 1256 mothers and 2512 twins resulting from spontaneous conception. In the controlled study 93 mothers and 186 twins from the research group were compared with 93 mothers and 186 newborns after spontaneous conception. In this group the mothers matched the research group in age, parity and birth year. The course of and complications during the pregnancy, and the course, complications and outcome of the birth as well as the characteristics of the newborns were compared.Results. Certain serious complications during the course of the pregnancy, including hypertension, gestation diabetes and threatened preterm labours, were no more frequent with the IVF group of mothers with twin pregnancy than with the control group. However more bleeding in the first trimester and less proteinuria were determined in comparison to the control group. During the course of birth and its outcome more premature labours were determined (62.3–68.8% vs. 51.4– 50.5%), a 6 to 7 days lower average gestation age, a coresponding birth weight, three times more elective and urgent caesarean sections were determined for the IVF group than for the control group and the differences were all statistically significant.Conclusions. Multiple pregnancies are a complication of an IVF-ET procedure. Women who conceive after an IVF-ET procedure and with a twin pregnancy outcome are not subject to any more danger than pregnant women after spontaneous conception. Children are born somewhat earlier and are therefore lighter, however the perinatal outcome of newborns is no different and the morbidity and mortality rates are similar to that of newborns after spontaneous conception.
- Published
- 2003
18. MULTIPLE PREGNANCIES AFTER INTRACYTOPLASMIC SPERM INJECTION (ICSI)
- Author
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Branko Zorn, Irma Virant Klun, Sašo Drobnič, Tomaž Tomaževič, and Helena Meden Vrtovec
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intracytoplasmic sperm injection ,twinning pregnancy ,monozygotic twinning ,blastocyst ,blastocyst freezingthawing ,Medicine - Abstract
Background. Because of complications related to multiple pregnancies after in vitro fertilization this pathology represent a real problem. Intracytoplasmic sperm injection (ICSI) may lead to higher risk in developing monozygotic pregnancies. We sought to investigate whether the multiple pregnancies after ICSI differ of those consecutive to classical in vitro fertilization (IVF) and if counseling for transfering one or at most two embryos is efficient in preventing multiple pregnancies.Methods. We analyzed retrospectively data concerning the incidence of multiple pregnancies before and after the transfer of limited number of embryos.Results. In transfering two cleaving-stage embryos (day 2) or blastocysts (day 5), when pregnancy rate is high, the incidence of multiple pregnancies is 25 and 17%. After transfer of one blastocyst the highest the pregnancy rate and the lowest the incidence of multiple pregnancies.Conclusions. The best way to avoid multiple pregnancies consist in transferring one or at most two embryos. The monozygotic twin pregnancy we observed was consecutive to the transfer of frozen-thawed blastocyst.
- Published
- 2003
19. TWIN PREGNANCY AFTER THE TRANSFER OF TWO EMBRYOS
- Author
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Lili Bačer Kermavner, Irma Virant Klun, Brigita Valentinčič Gruden, Jerneja Kmecl, Jožica Mivšek, Tomaž Tomaževič, Martina Ribič Pucelj, Andrej Vogler, Eda Bokal Vrtačnik, Branko Zorn, Sašo Drobnič, Bojana Pinter, and Helena Meden Vrtovec
- Subjects
twin pregnancy ,blastocyst ,embryo transfer ,Medicine - Abstract
Background. Twin pregnancy rates following the transfer of two embryos in in vitro fertilization (IVF) treatment are high. Therefore, the aim of this study was to evaluate twin pregnancy rates in regard to the developmental stage of the embryo, patient age, and cause of infertility.Methods. A retrospective analysis involved 1222 IVF procedures. Overall pregnancy rates and twin pregnancy rates following the transfer of two blastocysts or two cleavage-stage embryos were assessed. The blastocyst group was divided into four age subgroups, and into four subgroups by the cause of infertility.Results. After the transfer of two blastocysts or two cleavagestage embryos the overall pregnancy rates (45% vs. 9%) and the twin pregnancy rates (18% vs. 5%) were significantly higher in the blastocyst group. The effects of patient age and the transfer of two blastocysts on the overall pregnancy and twin pregnancy rates were significantly greater in the subgroups of patients aged ≤ 30 years (21%) and 31–34 years (20%) than in older patients (35–38 years = 15.7%; ≥ 39 years = 9%). In the blastocyst group the twin pregnancy rate was significantly higher in patients with tubal (21%) and endocrinological causes of infertility (24.5%) than in patients with endometriosis (7%) and uterine malformations (12.5%).Conclusions. After the transfer of two blastocysts twin pregnancy rates are significantly higher in patients with tubal factor or endocrinological causes of infertility younger than 34 years. In this population of women the risk of twin pregnancy can be avoided by the transfer of a single embryo – most developed blastocyst.
- Published
- 2003
20. Vzroki zdravljenja sterilnosti pri ženski
- Author
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Tomaž Tomaževič
- Subjects
Nursing ,RT1-120 - Published
- 1984
21. Urgentna (nujna) stanja v ginekologiji (nadaljevanje in konec)
- Author
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Tomaž Tomaževič
- Subjects
Nursing ,RT1-120 - Published
- 1980
22. Prvo rojstvo otroka bolnici po zdravljenju raka materničnega vratu stadija IB1 z ohranitvijo rodne funkcije v UKC-LJ
- Author
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Milan Čavić, Ana Ranc, Branko Cvjetičanin, Tomaž Tomaževič, and Borut Kobal
- Subjects
ohranitev rodnosti ,maternični vrat ,rak ,lcsh:R ,lcsh:Medicine ,vaginalna radikalna trahelektomija - Abstract
Rak materničnega vratu lahko prizadene ženske v rodnem obdobju. V stadiju IB1 je mogoče pri zdravljenju rakave bolezni ohraniti rodno funkcijo ženske z radikalno trahelektomijo in odstranitvijo medeničnih bezgavk.To je operacija, pri kateri se odstrani maternični vrat in paracervikalno tkivo (parametriji) v kombinaciji z odstranitvijo medeničnih bezgavk, telo maternice pa se ohrani. Predstavljamo primer 32-letne nulipare z rakom materničnega vratu stadija 1B1. Bolnica je bila zdravljena radikalno z ohranitvijo rodne funkcije in je po zdravljenju rodila donošenega otroka.
- Published
- 2018
23. Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI
- Author
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H. Ban-Frangež, B. Požlep, Irma Virant-Klun, Tomaž Tomaževič, Eda Vrtačnik-Bokal, and Ivan Verdenik
- Subjects
Adult ,Septate ,medicine.medical_specialty ,Pregnancy Rate ,medicine.medical_treatment ,Slovenia ,Fertilization in Vitro ,Hysteroscopy ,Intracytoplasmic sperm injection ,Pregnancy ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,Retrospective Studies ,Uterine septum ,Gynecology ,Arcuate uterus ,Obstetrics ,business.industry ,Uterus ,Obstetrics and Gynecology ,Embryo Transfer ,medicine.disease ,Embryo transfer ,Abortion, Spontaneous ,Pregnancy rate ,Reproductive Medicine ,Case-Control Studies ,embryonic structures ,Female ,business ,Infertility, Female ,Live Birth ,Embryo quality ,Developmental Biology - Abstract
A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P
- Published
- 2010
- Full Text
- View/download PDF
24. The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls
- Author
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M. Ribič-Pucelj, E. Vrtačnik Bokal, Ivan Verdenik, H. Ban-Frangež, Tomaž Tomaževič, and Irma Virant-Klun
- Subjects
Adult ,Infertility ,medicine.medical_specialty ,Pregnancy Rate ,medicine.medical_treatment ,Fertilization in Vitro ,Hysteroscopy ,Abortion ,Intracytoplasmic sperm injection ,Pregnancy ,Risk Factors ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,reproductive and urinary physiology ,Retrospective Studies ,Uterine septum ,Gynecology ,medicine.diagnostic_test ,urogenital system ,Arcuate uterus ,Obstetrics ,business.industry ,Uterus ,Pregnancy Outcome ,Obstetrics and Gynecology ,medicine.disease ,Abortion, Spontaneous ,Pregnancy rate ,Reproductive Medicine ,Case-Control Studies ,embryonic structures ,Female ,business - Abstract
Objective(s): To evaluate the effect of hysteroscopic resection of a large uterine septum (Class V according to the American Fertility Society (AFS) classification) and of a small partial uterine septum (Class VI according to AFS classification or arcuate uterus) on the abortion rate in pregnancies after IVF and ICSI. Study design: The retrospective matched control study included 31 women who conceived following IVF or ICSI before hysteroscopic resection of a large (12 women) or small partial (19 women) uterine septum and 106 women who conceived following IVF or ICSI after hysteroscopic resection of a large (49 women) or small partial (57 women) uterine septum. For each pregnancy in the study group, we found two consecutive pregnant control women from the IVF/ICSI registry who had a normal uterus and were matched for age, BMI, stimulation protocol and the use of IVF or ICSI and for various infertility causes. The abortion/pregnancy rate was the main outcome measure. Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4 cm long yellow tip of the electric knife to the length of the resected septum. Results: The abortion rate before hysteroscopic metroplasty was significantly higher, both in women with a small partial septum (78.9% before resection vs. 23.7% in the normal controls, OR 12.08) and a large septum (83.3% before resection vs. 16.7% in normal controls, OR 25.00) compared to women with a normal uterus. After the surgery, the abortion rate was comparable to the abortion rate in women with normal uterus: in both women with a small partial and women with a larger septum. Conclusion(s): Similar to a large uterine septum, a small partial uterine septum is an important and hysteroscopically preventable risk factor for spontaneous abortion in pregnancies after IVF and ICSI.
- Published
- 2009
- Full Text
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25. Outcome of frozen-thawed blastocysts derived from gonadotropin releasing hormone agonist or antagonist cycles
- Author
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Irma Virant-Klun, Robert Medved, Tomaž Tomaževič, and Helena Meden-Vrtovec
- Subjects
Adult ,Agonist ,endocrine system ,medicine.medical_specialty ,Pregnancy Rate ,medicine.drug_class ,medicine.medical_treatment ,Fertilization in Vitro ,Gonadotropin-releasing hormone ,Buserelin ,Gonadotropin-Releasing Hormone ,Andrology ,Ovulation Induction ,Pregnancy ,Internal medicine ,Gonadotropin-releasing hormone agonist ,Genetics ,medicine ,Humans ,Genetics (clinical) ,Retrospective Studies ,Cryopreservation ,Original Paper ,business.industry ,Pregnancy Outcome ,Antagonist ,Obstetrics and Gynecology ,Fertility Agents, Female ,General Medicine ,humanities ,Pregnancy rate ,Blastocyst ,Endocrinology ,Reproductive Medicine ,Female ,Ovulation induction ,business ,Live birth ,Live Birth ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology ,medicine.drug - Abstract
Purpose: The aim of this retrospective study was to compare the outcome of frozen-thawed blastocysts derived from the cycles using controlled ovarian stimulation with GnRH agonists vs. GnRH antagonists. Methods: Survival, pregnancy and cumulative live birth rates in 231 freeze-thaw cycles derived from the GnRH agonist cycles (GnRH agonist group), and in 175 freeze-thaw cycles derived from the GnRH antagonist cycles (GnRH antagonist group) were compared. Results: In the GnRH agonist group significantly higher proportion of blastocysts survived the thawing procedure than in the GnRH antagonist group (86.1% versus 78.5%; p < 0.01). The differences in cumulative live birth rates did not differ significantly between the groups: in the GnRH agonist group the cumulative live birth rate was 16.5%, and in the GnRH antagonist group it was 14.2%. Conclusions: Frozen-thawed blastocysts derived from the GnRH agonist cycles have better survival rates and similar cumulative live birth rates than those derived from the GnRH antagonist cycles.
- Published
- 2006
- Full Text
- View/download PDF
26. Small uterine septa (AFS Class 6) represent an important risk variable for preterm birth and spontaneous abortion
- Author
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Andrej Vogler, Tanja Premru-Srsen, M. Ribič-Pucelj, Bojana Pinter, H Ban, Tomaž Tomaževič, Sašo Drobnič, Branko Zorn, Eda Vrtačnik-Bokal, and Ivan Verdenik
- Subjects
Gynecology ,Fetus ,medicine.medical_specialty ,business.industry ,Obstetrics ,Incidence (epidemiology) ,Birth weight ,General Medicine ,Abortion ,medicine.disease ,Intensive care unit ,Birth rate ,law.invention ,Dissection ,law ,Medicine ,business ,Uterine septum - Abstract
We compared pregnancy outcomes before and after hysteroscopic dissection of small and large uterine septa. The study involved 933 women after hysteroscopic dissection of a uterine septum: 483 women with a large septum (1.5 cm to total) and 450 women with a small septum (1–1.5 cm). The structure of 957 pregnancies before the operation differed significantly from the structure of 564 pregnancies after the operation (P
- Published
- 2004
- Full Text
- View/download PDF
27. Increased ammonium in culture medium reduces the development of human embryos to the blastocyst stage
- Author
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Andrej Vogler, Irma Virant-Klun, Mladen Krsnik, Helena Meden-Vrtovec, Eda Vrtačnik-Bokal, and Tomaž Tomaževič
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Embryonic Development ,Fertilization in Vitro ,Biology ,Intracytoplasmic sperm injection ,Andrology ,chemistry.chemical_compound ,medicine ,Humans ,Ammonium ,Prospective Studies ,Sperm Injections, Intracytoplasmic ,Blastocyst ,reproductive and urinary physiology ,Gynecology ,In vitro fertilisation ,urogenital system ,Osmolar Concentration ,Embryogenesis ,Obstetrics and Gynecology ,Embryo ,Embryo, Mammalian ,Sequential media ,Culture Media ,Quaternary Ammonium Compounds ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,Spectrophotometry ,embryonic structures ,Female ,therapeutics - Abstract
The objective of this prospective study was to evaluate the effect of ammonium accumulated in sequential media and determined by enzymatic spectrophotometric method on the blastocyst development in 281 human embryos from 100 stimulated and natural in vitro fertilization (IVF) cycles. Ammonium concentration was increased in 62% of cycles and was correlated negatively with the blastocyst development after classical IVF, but not after intracytoplasmic sperm injection (ICSI).
- Published
- 2006
- Full Text
- View/download PDF
28. Hysterosalpingo-contrast sonography for infertility investigation
- Author
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Tomaž Tomaževič and Boštjan Lovšin
- Subjects
Adult ,Infertility ,medicine.medical_specialty ,media_common.quotation_subject ,Sensitivity and Specificity ,Fallopian Tube Patency Tests ,Young Adult ,Predictive Value of Tests ,Pregnancy ,medicine ,Humans ,Contrast (vision) ,Hysterosalpingo contrast sonography ,media_common ,Gynecology ,Obstetrics ,business.industry ,Reproducibility of Results ,Obstetrics and Gynecology ,General Medicine ,Fallopian Tube Diseases ,medicine.disease ,Hysterosalpingography ,medicine.anatomical_structure ,Female ,Laparoscopy ,business ,Infertility, Female ,Follow-Up Studies ,Fallopian tube - Published
- 2009
- Full Text
- View/download PDF
29. [Untitled]
- Author
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Helena Meden, Tomaž Tomaževič, Karel Zupančič, and Viktorija Žnidaršič
- Subjects
Gynecology ,Infertility ,medicine.medical_specialty ,business.industry ,Reproductive medicine ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,Human genetics ,Embryo transfer ,Reproductive Medicine ,Informed consent ,Oocyte donation ,Family medicine ,Genetics ,Medicine ,business ,Genetics (clinical) ,Developmental Biology - Published
- 2000
- Full Text
- View/download PDF
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