A termékenység megőrzése céljából gyermekkorban végzett petefészekszövet-fagyasztás első hazai esete

A gyermek onkohematológiai ellátás fejlődésével, a javuló gyógyulási eredményekkel előtérbe kerültek a betegek hosszú távú életminőségében szerepet játszó tényezők. Bizonyos, az onkohematológiában használt kezelések gonadotoxikus hatásúak, károsíthatják a fertilitást, emiatt nemzetközi szinten a termékenységmegőrző eljárások egyre nagyobb teret hódítanak. Magyarországon ezek az eljárások gyermekek számára jelenleg csak részben érhetők el. Az egyik ilyen fontos termékenységmegőrző eljárás a petefészekszövet-fagyasztás és az ezt követő autotranszplantáció. Közleményünkben bemutatjuk a Semmelweis Egyetem II. Gyermekgyógyászati Klinikája, valamint Szülészeti és Nőgyógyászati Klinikája közti együttműködés keretében történt petefészekszövet-fagyasztást, mely az első prepubertáskorban alkalmazott hazai eset. A II. Gyermekgyógyászati Klinikán recidív lymphomatoid granulomatosis miatt kezelt, csontvelő-transzplantációra felterjesztett gyermek a kezelése során tervezetten olyan kemoterápiás kondicionáló kezelésben részesül, mely magas kockázattal petefészek-elégtelenséghez, következményes meddőséghez vezethet. Emiatt a család kérését figyelembe véve, a gonadotoxikus kezelést megelőzően, az onkoteam és a szakmai grémium a termékenység megőrzése céljából történő petefészekszövet-fagyasztás (ovarium-krioprezerváció) mellett döntött. A szükséges engedélyek birtokában 2021 decemberében a Gyermekgyógyászati Klinikán a gyermek jobb oldali petefészkét laparoszkópos úton eltávolítottuk, és a Szülészeti és Nőgyógyászati Klinika Asszisztált Reprodukciós Osztályára szállítottuk, ahol előkészítést követően a szövetmintákat mélyfagyasztottuk hosszú távú tárolás és későbbi autotranszplantáció céljából. Az onkohematológia fejlődésével növekszik az igény a fertilitásmegőrző eljárások iránt. Ezek egy része Magyarországon a felnőtt lakosság számára elérhető, de gyermekkorú betegeknél ilyen beavatkozásokra rutinszerűen még nincs lehetőség. A cikkben bemutatott, egyedi engedélyeztetéssel elvégzett eljárás jelenleg ma Magyarországon gyermekek esetében úttörőnek számít. A szerzők célja a jövőben egy olyan onkofertilitási hálózat létrehozása, mely a későbbiekben alapul szolgálhat a hasonló esetek minél gördülékenyebb ellátásához

The importance of cytoplasmic strings during early human embryonic development

Objectives: During human in vitro fertilisation (IVF) treatments, embryologists attempt to select the most viable embryos for embryo transfer (ET). Previously, embryos were evaluated based on light microscopic morphological parameters. However, this is currently accomplished by morphokinetic analysis of time-lapse recordings. This technique provides us the opportunity to observe cytoplasmic strings at the blastocyst stage. The aim of this work was to examine the relationship between the presence of cytoplasmic strings (CS) and the embryo viability in human in vitro fertilised embryos.Study design: Herein, we present an evaluation of the morphokinetic data on the development of embryos obtained during IVF treatments performed at the Division of Assisted Reproduction between December 2020 and March 2021. The dynamics of embryo development, embryo morphology, and morphokinetic scores generated by a time-lapse system were compared between the presence of cytoplasmic strings (CS+) and their absence (CS-) at the blastocyst stage.Results: The development of 208 embryos from 78 patients was examined. Moreover, 81.2% of the embryos had CS in the blastocyst stage; 77% of CS existed in embryos created by conventional IVF, while 86% of CS existed in embryos fertilised by intracytoplasmic sperm injection (ICSI) (p = 0.08). A greater number of CS+ embryos developed into a higher quality blastocyst (52.1% vs. 20.5%, p = 0.02). The morphokinetic score values characterising the development of embryos, such as Known Implantation Data Score (KIDScore) and Intelligent Data Analysis (iDAScore), were higher in CS+ groups (KID: 6.1 ± 2.1 vs. 4.7 ± 2.07; iDA: 8.0 ± 1.9 vs. 6.8 ± 2.3, p < 0.01). The dynamics of the early embryo development were similar between the two groups; however, CS+ embryos reached the blastocyst stage significantly earlier (tB: 103.9 h vs. tB: 107.6 h; p = 0.001).Conclusion: Based on our results, the number of embryos with cytoplasmic strings was higher than that without cytoplasmic strings, and its presence is not related to the fertilisation method. These embryos reached the blastocyst stage earlier, and their morphokinetic (KIDScore and iDAScore) parameters were better. All these results suggest that the presence of CS indicates higher embryo viability. The examination of this feature may help us make decisions about the embryos with higher implantation potential

Prospective-randomized study comparing clinical outcomes of IVF treatments where embryos were cultured individually or in a microwell group culture dish

Culturing embryos together in a microdrop of media may improve embryo quality, based on the results of animal studies, however individual identification of the embryos in such a system is not possible. The microwell group culture dish contains 9 or 16 microwells with a minimal well-to-well distance and a specific well morphology that facilitates paracrine and autocrine effects. The microwell group culture dish enables individual identification of the embryos while providing the environment that comes with similar benefits as group culture. Our aim was to investigate whether embryo culture in the microwell group culture dish (Primo Vision Dish, Vitrolife) improves IVF outcomes compared to individual culture in human IVF treatment. Five hundred thirty-two IVF-ET cycles were enrolled in this prospective randomized study in a university hospital. IVF cycles were randomized into microwell group culture and individual culture groups. Primary outcome measure was clinical pregnancy rate and secondary outcome measures were embryo quality, fertilization, implantation, delivery and embryo utilization rates. Fertilization rate in ICSI cycles was significantly higher in the microwell group culture group (70.6% vs. 64.9%, P = 0.001). Clinical pregnancy rate was 50.8% in the group culture and 40.6% in the individual culture (P = 0.022). Live birth rate was 41.5% in microwell and 32.9% in individual culture (P = 0.0496). Embryo utilization rate was higher in microwell group culture than in individual culture (80.6% vs. 75.0%; P < 0.001). Microwell group culture has a beneficial effect on IVF outcome and it also allows following up individual embryo development

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

<p>Abstract</p> <p>Background</p> <p>Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome.</p> <p>Methods</p> <p>Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant.</p> <p>Results</p> <p>The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17).</p> <p>Conclusion</p> <p>Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.</p

Predictive value of oocyte morphology in human IVF: a systematic review of the literature

BACKGROUND: Non-invasive selection of developmentally competent human oocytes may increase the overall efficiency of human assisted reproduction and is regarded as crucial in countries where legal, social or religious factors restrict the production of supernumerary embryos. The purpose of this study was to summarize the predictive value for IVF success of morphological features of the oocyte that can be obtained by light or polarized microscopic investigations. METHODS: Studies about oocyte morphology and IVF/ICSI outcomes were identified by using a systematic literature search. RESULTS: Fifty relevant articles were identified: 33 analysed a single feature, 9 observed multiple features and investigated the effect of these features individually, 8 summarized the effect of individual features. Investigated structures were the following: meiotic spindle (15 papers), zona pellucida (15 papers), vacuoles or refractile bodies (14 papers), polar body shape (12 papers), oocyte shape (10 papers), dark cytoplasm or diffuse granulation (12 papers), perivitelline space (11 papers), central cytoplasmic granulation (8 papers), cumulus–oocyte complex (6 papers) and cytoplasm viscosity and membrane resistance characteristics (2 papers). None of these features were unanimously evaluated to have prognostic value for further developmental competence of oocytes. CONCLUSIONS: No clear tendency in recent publications to a general increase in predictive value of morphological features was found. These contradicting data underline the importance of more intensive and coordinated research to reach a consensus and fully exploit the predictive potential of morphological examination of human oocytes

Intra-uterine insemination versus fallopian tube sperm perfusion for non-tubal infertility

Background Controlled ovarian hyperstimulation (COH) combined with intrauterine insemination (IUI) is commonly offered to couples with subfertility that does not involve the fallopian tubes. Another method is fallopian tube sperm perfusion (FSP). This technique ensures the presence of higher sperm densities in the fallopian tubes at the time of ovulation than does standard IUI. The aim of this review was to determine whether FSP and IUI differ in improving the probability of conception. Objectives To investigate whether pregnancy and live birth outcomes differ between fallopian tube sperm perfusion and intrauterine insemination in the treatment of non-tubal subfertility. Search strategy We searched the Menstrual Disorders and Subfertility Group Trials Register (October 2008), MEDLINE (January 1966 to October 2008), and EMBASE (January 1988 to October 2008). Abstracts of the American Society for Reproductive Medicine (1987 to 2008) and European Society for Human Reproduction and Embryology (1987 to 2008) meetings were searched using the same key or text words. Selection criteria Only truly randomised controlled studies comparing FSP with IUI were included in this review. Couples with non-tubal subfertility who have been trying to conceive for at least one year were included. Data collection and analysis Two review authors independently selected the trials for inclusion based on the quality of the studies. Main results Eight studies involving 595 couples were included in the meta-analysis. Only one study reported the live birth rate and there was no evidence of a difference between FSP and IUI (OR 1.2, 95% CI 0.39 to 3.5). There was no evidence of a difference between FSP and IUI for clinical pregnancy per couple (OR 1.2, 95% CI 0.79 to 1.7). A subgroup analysis which included couples with unexplained subfertility only (n = 239) did not report any difference between FSP and IUI (OR 1.6, 95% CI 0.89to2.8). Authors' conclusions For non-tubal subfertility, the results indicate no clear benefit for FSP over IUI. Therefore the advice offered to subfertile couples regarding the comparative use of FSP versus IUI in the treatment of non-tubal subfertility should reflect thi

Egyszer volt, hol nem volt: a fogyatékosság megjelenése a Grimm mesékben

A fogyatékosság egyidős az emberiséggel, akár csak a mesék. A meséken keresztül betekintést nyerhetünk különböző kultúrák és korok világába, világnézetébe. Egyes mesékből többek között azt is megtudhatjuk, hogyan viszonyult a társadalom a fogyatékos személyekhez. Szakdolgozatomban arra keresem a választ, hogyan jelennek meg a fogyatékos személyek a Grimm mesékben, hogyan viszonyul hozzájuk a környezetük és milyen szerepet szántak nekik a történetben

Impact of highly purified versus recombinant follicle stimulating hormone on oocyte quality and embryo development in intracytoplasmic sperm injection cycles

The quality of oocytes and developing embryos are the most relevant factors determining the success of an in vitro fertilization (IVF) treatment. However, there are very few studies analyzing the effects of different gonadotrophin preparations on oocyte and embryo quality. A retrospective secondary analysis of data collected from a prospective randomized study was performed to compare highly purified versus recombinant follicle stimulating hormone (HP-FSH vs. rFSH). The main outcome measures were quantity and quality of oocytes and embryos, dynamics of embryo development, cryopreservation, clinical pregnancy and live birth rate. The number of retrieved and of mature (MII) oocytes showed no significant differences. Fertilization rate was significantly higher in the HP-FSH group (68.9% vs. 59.9%, p = 0.01). We also found significantly higher rate of cryopreserved embryos per all retrieved oocytes (23.4% vs. 14.5%, p = 0.002) in the HP-FSH group. There were no significant differences in clinical pregnancy and in live birth rates. Oocytes obtained with HP-FSH stimulation showed higher fertilisability, whereas pregnancy and live birth rates did not differ between the groups. However, patients treated with HP-FSH may benefit from the higher rate of embryos capable for cryopreservation, suggesting that cumulative pregnancy rates might be higher in this group

Importance of cytoplasmic granularity of human oocytes in In vitro fertilization treatments

The aim of this study was to examine the effect of different stimulation protocols on oocyte granularity and to determine the influence of cytoplasmic granularity on further embryo development. A total of 2448 oocytes from 393 intracytoplasmic sperm injection (ICSI) cycles were analysed retrospectively. Oocytes were classified into 5 groups according to cytoplasmic granularity. (A) no granule or 1–2 small (5 μm); (D) refractile body; (E) dense centrally located granular area. Correlation between characteristics of hormonal stimulation, oocyte granularity and embryo development was analysed. The occurrence of cytoplasmic granularity was influenced by the patient’s age and characteristics of stimulation. The type of granulation had no effect on fertilization rate and zygote morphology. However, some type of granulation resulted in a lower cleavage rate and more fragmented embryos. Our results provided additional information on how hormonal stimulation affects oocyte quality. While cytoplasmic granularity seems not to have an effect on fertilization and embryo development, the presence of refractile body in the oocyte is associated with reduced cleavage rates and impaired embryo development