PURPOSE: To evaluate the decline in transferable embryos in preimplantation genetic testing for aneuploidy (PGT-A) cycles due to (a) non-biopsable blastocyst quality, (b) failure of genetic analysis, (c) diagnosis of uniform numerical or structural chromosomal aberrations, and/or (d) chromosomal aberrations in mosaic constitution. METHODS: This retrospective multicenter study comprised outcomes of 1562 blastocysts originating from 363 controlled ovarian stimulation cycles, respectively, 226 IVF couples in the period between January 2016 and December 2018. Inclusion criteria were PGT-A cycles with trophectoderm biopsy (TB) and next generation sequencing (NGS). RESULTS: Out of 1562 blastocysts, 25.8% were lost due to non-biopsable and/or non-freezable embryo quality. In 10.3% of all biopsied blastocysts, genetic analysis failed. After exclusion of embryos with uniform or chromosomal aberrations in mosaic, only 18.1% of those originally yielded remained as diagnosed euploid embryos suitable for transfer. This translates into 50.4% of patients and 57.6% of stimulated cycles with no euploid embryo left for transfer. The risk that no transfer can take place rose significantly with a lower number of oocytes and with increasing maternal age. The chance for at least one euploid blastocyst/cycle in advanced maternal age (AMA)-patients was 33.3% compared to 52.1% in recurrent miscarriage (RM), 59.8% in recurrent implantation failure (RIF), and 60.0% in severe male factor (SMF). CONCLUSIONS: The present study demonstrates that PGT-A is accompanied by high embryo drop-out rates. IVF-practitioners should be aware that their patients run a high risk of ending up without any embryo suitable for transfer after (several) stimulation cycles, especially in AMA patients. Patients should be informed in detail about the frequency of inconclusive or mosaic results, with the associated risk of not having an euploid embryo available for transfer after PGT-A, as well as the high cost involved in this type of testing.
- MeSH
- aneuploidie MeSH
- blastocysta patologie MeSH
- genetické testování metody MeSH
- lidé MeSH
- preimplantační diagnóza * metody MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
A recent study published in Human Reproduction claimed that uterine lavage offers a non-surgical, minimally invasive strategy for the recovery of human embryos from fertile women who do not want or need IVF for medical reasons but who desire preimplantation genetic testing (PGT) for embryos. To prove this hypothesis, the researchers recruited dozens of young Mexican women. The prospective oocyte donors underwent ovarian stimulation to induce the production of multiple mature oocytes. Subsequently, these women were inseminated by donor semen. A few days later, the developing embryos were collected by uterine lavage (uterine flushing) and subjected to genetic testing for aneuploidies (PGT-A). Oocyte donors with persistently elevated hCG levels, indicating the implantation of one or more embryos after uterine lavage, had to undergo uterine curettage and/or treatment with methotrexate. A critical opinion paper discussing the aforementioned study was published by De Santis and colleagues and has raised critical issues that are largely technical in nature. However, this opinion paper neglects-from our point of view-critical issues of the Mexican study regarding ethical principles and moral standards in human research. These aspects are summarized below.
- MeSH
- aneuploidie MeSH
- biomedicínský výzkum etika MeSH
- dospělí MeSH
- fertilizace in vitro etika MeSH
- implantace embrya genetika MeSH
- lidé MeSH
- odběr oocytu etika MeSH
- oocyty cytologie růst a vývoj MeSH
- preimplantační diagnóza etika MeSH
- přenos embrya etika MeSH
- reprodukční lékařství etika MeSH
- sperma cytologie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Successful embryo implantation depends on a well-timed maternal-embryonic crosstalk. Human chorionic gonadotropin (hCG) secreted by the embryo is known to play a key role in this process and to trigger a complex signal transduction cascade allowing the apposition, attachment, and invasion of the embryo into the decidualized uterus. Production of hCG was reported to be dependent on blastocyst quality and several articles suggested that intrauterine hCG injection increases pregnancy and implantation rates in IVF patients. However, no study has as yet analysed birth rates as final outcome. Our objective was to determine whether clinical outcome after blastocyst transfer can be improved by intrauterine injection of hCG and whether this is dependent on blastocyst quality. METHODS: A prospective randomised study was conducted in two settings. In cohort A, hCG application was performed two days before blastocyst transfer. In cohort B, the administration of hCG occurred just prior to embryo transfer on day 5. For both cohorts, patients were randomised to either intrauterine hCG application or to the control group that received culture medium. Clinical outcome was analysed according to blastocyst quality of transferred embryos. RESULTS: The outcome of 182 IVF-cycles (cohort A) and 1004 IVF-cycles (cohort B) was analysed. All patients received a fresh autologous blastocyst transfer on day five. Primary outcomes were pregnancy rates (PR), clinical pregnancy rates (cPR), miscarriage rates (MR), and live birth rates (LBR). No improvement of clinical outcome after intrauterine hCG administration on day 3 (cohort A) or day 5 (cohort B) was found, independently of blastocyst quality transferred. The final outcome in cohort A: LBR after transfer of top blastocysts was 50.0 % with hCG and 53.3 % in the control group. With non-top blastocysts, LBR of 17.1 % (hCG) and 18.2 % (control) were observed (n.s.). In cohort B, LBR with top blastocysts was 53.3 % (hCG) and 48.4 % (control), with non-top blastocysts it came to 28.7 % (hCG) and 35.0 % (control). The differences between the groups were statistically not significant. Furthermore, we investigated a possible benefit of hCG administration in correlation with female age. In both age groups (<38 years and ≥ 38 years) we found similar LBR after treatment with hCG vs. medium. A LBR of 47.1 % vs. 48.7 % was obtained in the younger group and 26.6 % vs. 30.8 % in the older group. CONCLUSIONS: In contrast to previous studies indicating a substantial benefit from intrauterine hCG application in cleavage stage embryo transfers, in our study we could not find any evidence for improvement of clinical outcome in blastocyst transfer cycles, neither with top nor with non-top quality morphology.
- MeSH
- blastocysta účinky léků MeSH
- choriogonadotropin farmakologie terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- narození živého dítěte MeSH
- porodnost MeSH
- přenos embrya metody MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Publikační typ
- abstrakt z konference MeSH
Cíl studie: Práce porovnává vybrané koagulační parametry těhotných žen dlouhodobě léčených ve sledované graviditě preventivní dávkou nízkomolekulárního heparinu se zdravými těhotnými ženami bez heparinové prevence. Typ studie: Prospektivní studie. Název a sídlo pracoviště: Hematologický úsek, Ústav klinické biochemie a hematologie, Lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Plzeň. Metodika: Sledovali jsme koagulační parametry 67 těhotných žen s opakovanými potraty v anamnéze, které byly dlouhodobě léčené ve sledované graviditě preventivní dávkou LMWH a porovnali jsme je se zdravými těhotnými ženami neléčenými LMWH. Ženy byly laboratorně vyšetřované před graviditou a v 10., 20., 30. týdnu gravidity. Výsledky: Ačkoliv klinicky je úspěšnost podávaného LMWH vysoká, koagulační parametry těhotných žen dlouhodobě léčených LMWH nebyly statisticky významně odlišné od souboru kontrolních gravidních žen heparinem neléčených. Závěr: Na úspěšném zakončení těhotenství u žen s předchozími opakovanými potraty či patologickým vývojem plodu se podávání heparinu pravděpodobně uplatňuje jinými mechanismy než koagulačními (např. přes komplementový systém nebo přes sekreci prostaglandinů).
Objective: The aim of study was to compare plasma levels of selected coagulation parameters in pregnant women with long-term administration of low molecular weight heparin (LMWH) versus cohort of healthy women LMWHs untreated. Design: Prospective study. Setting: Department of Haematology, Institute of Clinical Biochemistry and Haematology, Charles University and University Hospital, Plzen. Methods: We examined 67 pregnant women with recurrent fetal loss in previous pregnant history treated by long-term prophylactic administration of LMWH. Blood samples were collected before gestation and at 10th, 20th, 30th gestational weeks. Results: Pregnant women with own history of recurrent fetal loss treated by the long-term prophylactic dose of LMWHs during pregnancy have the same values of the coagulation parameters as the control cohort in spite of fact that the clinical efficacy of administered LMWHs is high. Conclusion: Our results suggest that heparin may act by many unknown different mechanisms, such as inhibition of complement binding or secretion of prostaglandins.
- MeSH
- antikoagulancia terapeutické užití MeSH
- dospělí MeSH
- financování organizované MeSH
- habituální potrat prevence a kontrola MeSH
- hemokoagulace účinky léků MeSH
- heparin nízkomolekulární terapeutické užití MeSH
- koagulační faktory analýza MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
PROBLEM: The aim of study was to investigate identical female twins born in 1977 suffered from autoimmune diseases (twin A - Sjogren's syndrome, and twin B - systemic lupus erythematosus). METHOD OF STUDY: It was refer retrospective analysis of both sisters suffered beside autoimmune alterations (Sjogren's syndrome and systemic lupus erythematosus) also from gynecological diseases (twin A - praecancerosis of cervix uteri, twin B - carcinoma vaginae). RESULTS: Relationships between disease activities and severities in the female twins were similar and the treatments were directed according to clinical symptoms and laboratory results. Dramatic change, unfortunately, occurred with twin B. The reason may be the association between SLE activity (lupus nephritis), hematological complication (leukopenia) and oncological vaginal recidivation. CONCLUSION: Association between autoimmune disease and gynecological cancer (or praecancerosis) is major risk than without immunology deviation. Twin A is periodically gynecologically observed.
- MeSH
- dospělí MeSH
- dvojčata monozygotní MeSH
- fatální výsledek MeSH
- lidé MeSH
- nádory děložního čípku komplikace diagnóza patologie patofyziologie MeSH
- nádory vaginy komplikace diagnóza patologie patofyziologie MeSH
- nemoci u dvojčat MeSH
- prekancerózy komplikace diagnóza patologie patofyziologie MeSH
- retrospektivní studie MeSH
- Sjögrenův syndrom komplikace diagnóza patologie patofyziologie MeSH
- spinocelulární karcinom komplikace diagnóza patologie patofyziologie MeSH
- systémový lupus erythematodes komplikace diagnóza patologie patofyziologie MeSH
- těhotenství MeSH
- vedení porodu MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
PROBLEM: The present work was undertaken to investigate the occurence of autoantibodies to eight various phospholipids in time of urgent termination of the pregnancy (sectio caesarea) in patients in reproductive age with severe preeclamptic symptoms. METHOD OF STUDY: Autoantibodies against annexin V, ph-serine, ph-ethanolamine, ph-inositol, ph-DL-glycerol, cardiolipin, beta2-glycoprotein I (beta2-GPI), and phosphatidic acid were studied by ELISA methods. RESULTS: Increased levels of IgA-beta2-glycoprotein I, IgG-beta2-glycoprotein I, IgG- anti-ph-serine, and IgG-anticardiolipin were found in sera of preeclamptic women in the time of urgent sectio caesarea when compared to the control group with physiological pregnancy. CONCLUSION: Supposed increase in various antiphospholipid antibodies (aPLs) levels due to the stress during the short time of admission and a need for a quick medical decision to terminate the pregnancy was not unambiguously proven, but our results are evidently influenced by the current urgent life-saving treatment.
- MeSH
- antifosfolipidové protilátky krev MeSH
- beta-2-glykoprotein I imunologie MeSH
- dospělí MeSH
- ELISA MeSH
- fosfoserin imunologie MeSH
- lidé MeSH
- placentární oběh imunologie MeSH
- potrat léčebný MeSH
- preeklampsie krev imunologie patofyziologie terapie MeSH
- těhotenství MeSH
- trombóza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
94 l. : tab. ; 30 cm
To study in details women with repeated unexplained miscarriages by significant tests in reproductive immunology, in genetics, and by special coagulation tests. Analysis of all studied factors in patients with repeated spontaneous miscarriages. Proposalof new rational and early treatment up to delivery of healthy foetus and to physiological childbed. Our results in this applied research will serve as a basis for general praxis concerning the special treatment in women with pregnancy loss.
Sledování pacientek s opakovanými potraty významnými testy reprodukční imunologie, geneticky a hemokoagulačním vyšetřením. Analýza všech faktorů s ohledem na základní diagnozu. Navržení racionálního včasného léčebného postupu a zajištění pacientky do porodu zdravého plodu a fyziologického šestinedělí. Po zhodnocení všech dosažených výsledků tohoto aplikovaného výzkumu zavést do praxe metodický pokyn.
- MeSH
- antifosfolipidový syndrom komplikace MeSH
- fertilizace in vitro metody trendy využití MeSH
- placentární oběh MeSH
- samovolný potrat etiologie MeSH
- trombofilie genetika komplikace MeSH
- vyšetření krevní srážlivosti MeSH
- ženy MeSH
- Konspekt
- Gynekologie. Porodnictví
- NLK Obory
- gynekologie a porodnictví
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
PROBLEM: The aim of this study was to investigate frequencies of eight antiphospholipid antibodies (aPLs) in serum, four genetic thrombophilic factors and their mutual relation in 206 patients with repeated pregnancy loss (RPL). METHOD OF STUDY: Enzyme-linked immunosorbent assay was used for detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, DL-glycerol, phosphatidic acid, anti-annexin V, cardiolipin, and beta2-GPI. FV 1691G>A (Leiden mutation), FII 20210G>A mutation, MTHFR 677C>T and MTHFR 1298A>C variant genotypes were determined using a melting curve analysis of the PCR amplification product detected by the fluorescence resonance energy transfer. Genotypic distribution and allelic frequencies were calculated. Correlation between aPLs and thrombophilic factors was tested by chi-square and Fisher exact test. RESULTS: Our results show significantly increased prevalence of aPLs against ph-inositol (17-19.6% dependent on number of spontaneous miscarriages) and against ph-serine (18-25%). aPLs in IgG prevail. In 96% of the studied group, at least one risk factor was found (either aPLs positivity or thrombophilic factor). Both aPLs and thrombophilic factors were present in 43%. In the group of women with three or more RPLs, strong positive correlation of aPLs positivity and thrombophilic risk factors was observed. CONCLUSION: Antiphospholipide antibodies and genetic thrombophilic factors are important risk factors in the pathogenesis of RPL. Both autoantibodies against various kinds of phospholipides and genetic thrombophilic factors must be studied together in diagnosis of RPL for appropriate treatment
- MeSH
- antifosfolipidové protilátky biosyntéza genetika imunologie krev MeSH
- DNA sondy MeSH
- dospělí MeSH
- ELISA MeSH
- frekvence genu imunologie MeSH
- genotyp MeSH
- habituální potrat epidemiologie genetika imunologie MeSH
- kauzalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- trombofilie genetika imunologie MeSH
- výsledek těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH