In patients with testicular germ cell tumours (TGCT), sperm cryopreservation prior to anti-cancer treatment represents the main fertility preservation approach. However, it is associated with a low sperm recovery rate after thawing. Since sperm is a high-energy demanding cell, which is supplied by glycolysis and oxidative phosphorylation (OXPHOS), mitochondrial dysfunctionality can directly result in sperm anomalies. In this study, we investigated the bioenergetic pattern of cryopreserved sperm of TGCT patients in comparison with normozoospermic samples using two state-of-the-art methods: the Extracellular Flux Analyzer (XF Analyzer) and two-photon fluorescence lifetime imaging microscopy (2P-FLIM), in order to assess the contributions of OXPHOS and glycolysis to energy provision. A novel protocol for the combined measurement of OXPHOS (oxygen consumption rate: OCR) and glycolysis (extracellular acidification rate: ECAR) using the XF Analyzer was developed together with a unique customized AI-based approach for semiautomated processing of 2P-FLIM images. Our study delivers optimized low-HEPES modified human tubal fluid media (mHTF) for sperm handling during pre-analytical and analytical phases, to maintain sperm physiological parameters and optimal OCR, equivalent to OXPHOS. The negative effect of cryopreservation was signified by the deterioration of both bioenergetic pathways represented by modified OCR and ECAR curves and the derived parameters. This was true for normozoospermic as well as samples from TGCT patients, which showed even stronger damage within the respiratory chain compared to the level of glycolytic activity impairment. The impact of cryopreservation and pathology are supported by 2P-FLIM analysis, showing a significant decrease in bound NADH in contrast to unbound NAD(P)H, which reflects decreased metabolic activity in samples from TGCT patients. Our study provides novel insights into the impact of TGCT on sperm bioenergetics and delivers a verified protocol to be used for the assessment of human sperm metabolic activity, which can be a valuable tool for further research and clinical andrology.
- MeSH
- dospělí MeSH
- energetický metabolismus * MeSH
- germinální a embryonální nádory * metabolismus patologie MeSH
- glykolýza * MeSH
- kryoprezervace * metody MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- oxidativní fosforylace * MeSH
- spermie * metabolismus MeSH
- spotřeba kyslíku fyziologie MeSH
- testikulární nádory * metabolismus patologie MeSH
- uchování spermatu metody MeSH
- zachování plodnosti metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity. METHODOLOGY: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode. RESULTS: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001. CONCLUSION: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory děložního čípku * chirurgie MeSH
- předčasný porod prevence a kontrola etiologie epidemiologie MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- trachelektomie metody MeSH
- výsledek těhotenství MeSH
- zachování plodnosti * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: The management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing. METHODS: We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months). RESULTS: In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7-179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank). CONCLUSION: Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.
- MeSH
- adenokarcinom virologie patologie MeSH
- dospělí MeSH
- infekce papilomavirem * diagnóza virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory děložního čípku * virologie patologie diagnóza terapie MeSH
- následné studie MeSH
- Papillomaviridae izolace a purifikace MeSH
- retrospektivní studie MeSH
- třídění pacientů metody MeSH
- zachování plodnosti metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.
- MeSH
- cervix uteri chirurgie patologie MeSH
- lidé MeSH
- nádory děložního čípku * chirurgie patologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- staging nádorů MeSH
- těhotenství MeSH
- výsledek těhotenství MeSH
- zachování plodnosti * metody MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Tento článek, založený na rešerších literatury publikované do června 2023 v databázích Web of Science (WoS), Scopus, PubMed/Medline, se zaměřením na „breast cancer“ a „fertility preservation“, rozebírá nejdůležitější aspekty a kontroverze péče o reprodukční zdraví žen s karcinomem prsu. Protinádorová léčba účinně potlačuje maligní bujení, nicméně i přes pokrok v medicíně může dojít k poškození gonád. Znalost těchto rizik a funkční spolupráce mezi onkology a lékaři centra ochrany reprodukce jsou pro pacientku zásadní. Moderní postupy ochrany reprodukce se z pohledu reprodukční medicíny jeví jako účinné a bezpečné, i když mezi onkology a gynekology není plný konsenzus.
This article, based on a review of the literature until Jun 2023 in Web of Science (WoS), Scopus and PubMed/Medline databases, focused on “breast cancer” and “fertility preservation”, summarizes aspects and reproductive health care controversies during oncological treatment in female breast cancer patients. Current oncological treatment destroys malignant growth effectively, despite advances in medicine ovarian failure can occur. Knowledges about these risks and functional collaboration between oncologists and gynecologists are essential. Modern fertility preservation procedures are effective and safe from a gynecologist's perspective, although there is not a full consensus among oncologists and gynecologists.
- MeSH
- asistovaná reprodukce MeSH
- gonády účinky léků účinky záření MeSH
- homologní transplantace metody MeSH
- kryoprezervace MeSH
- lidé MeSH
- nádory prsu * farmakoterapie radioterapie MeSH
- odběr oocytu metody MeSH
- týmová péče o pacienty MeSH
- zachování plodnosti * metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- analýza spermatu MeSH
- antimülleriánský hormon analýza MeSH
- infertilita * prevence a kontrola MeSH
- lidé MeSH
- rizikové faktory MeSH
- služby preventivní péče * metody MeSH
- zachování plodnosti metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- novinové články MeSH
- MeSH
- imunoterapie ekonomika MeSH
- lidé MeSH
- onkologická péče - zařízení trendy MeSH
- triple-negativní karcinom prsu * genetika komplikace terapie MeSH
- zachování plodnosti metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- zprávy MeSH
Cíl: Shrnout aktuální možnosti kryokonzervace ovariální tkáně jako jednu z dalších možných metod pro zachování plodnosti u žen. Metodika: Literární přehled získaný ze studií a prací týkajících se kryokonzervace ovariální tkáně. Závěr: Kryokonzervace ovariální tkáně a její následná transplantace má významný potenciál pro zachování plodnosti nejen pro prepubertální a onkologické pacientky, ale také pro pacientky s různými zdravotními indikacemi vedoucími k předčasné ovariální insuficienci. Pro zachování co nejlepší kvality oocytů v kryokonzervované ovariální tkáni je nezbytné neustále optimalizovat, standardizovat a porovnávat jak kryokonzervační protokoly, postupy a strategie, tak i proces rozmražení ovariální tkáně s její následnou transplantací.
Objective: To summarize the current possibilities of ovarian tissue cryopreservation as one of the other possible methods for fertility preservation in women. Methods: Literature review obtained from studies and literature related to ovarian tissue cryopreservation. Conclusion: Cryopreservation of ovarian tissue and its subsequent transplantation has a significant potential for preserving fertility not only for prepubertal and oncological patients, but also for patients with various medical indications leading to premature ovarian insufficiency. In order to maintain the best possible quality of oocytes in cryopreserved ovarian tissue, it is necessary to constantly optimize, standardize and compare both cryopreservation protocols, procedures and strategies, as well as the process of thawing ovarian tissue with its subsequent transplantation.
- Klíčová slova
- onkofertilita, kryokonzervace ovariální tkáně, pomalé mražení, in vitro maturace,
- MeSH
- asistovaná reprodukce MeSH
- fertilizace in vitro MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- odběr oocytu metody MeSH
- odběr tkání a orgánů MeSH
- zachování plodnosti * metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Cíl: Endometrióza je chronické onemocnění s relativně vysokou prevalencí v ženské populaci. Jak nemoc samotná, tak i její chirurgická léčba mohou nepříznivě ovlivnit plodnost pacientek. Z toho důvodu se endometrióza nabízí jako možná indikace k ochraně reprodukce metodami kryoprezervace. Cílem práce je prezentovat současné poznatky o možnostech ochrany reprodukce v této subpopulaci. Metodika: Rešerše relevantní literatury v databázích PubMed/Medline, Web of Science a Scopus. Výsledky: Ochrana reprodukce metodami kryoprezervace se dosud využívala zejména v péči o onkologicky nemocné ženy. S narůstajícími zkušenostmi se výrazně zvýšila efektivnost i dostupnost těchto metod a indikační spektrum bylo rozšířeno na vybraná benigní onemocnění, jako je právě endometrióza. V současnosti jsou v praxi zavedené tři techniky: kryoprezervace embryí, kryoprezervace oocytů a kryoprezervace ovariální tkáně. Nejčastěji se využívá kryoprezervace oocytů, která je pro pacientku nejvýhodnější a dle dostupných dat představuje efektivní způsob, jak rizikovým pacientkám s endometriózou zvýšit šanci na budoucí graviditu. Smyslem je realizace ochrany reprodukce před plánovaným operačním výkonem. Závěr: Dia gnóza endometriózy negativně ovlivňuje fertilitu žen. Pro část pacientek je řešením ochrana reprodukce metodami kryoprezervace. K definování přesných, prakticky aplikovatelných indikačních kritérií, potenciálních rizik postupů a jejich benefitů i nákladové efektivnosti je potřeba dalších klinických studií.
: Objective: Endometriosis is a chronic disease with a relatively high prevalence in the female population. Both the disease itself and its surgical treatment can adversely affect the fertility of patients. For this reason, endometriosis is offered as a possible indication for fertility preservation by cryopreservation methods. The aim of this paper is to present the current knowledge on the options of fertility preservation in this subpopulation. Methods: Search of relevant literature in PubMed/Medline, Web of Science and Scopus databases. Results: Fertility preservation by cryopreservation methods has so far been used mainly in the care of women with cancer. With increasing experience, the effectiveness and availability of these methods have increased significantly and the indication spectrum has been extended to selected benign diseases such as endometriosis. Three techniques are currently established in practice: embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation is the most commonly used technique, since it is the most advantageous for the patient and, according to the available data, is an effective way to increase the chances of future pregnancy for patients with endometriosis The purpose is to realize the protection of reproduction before the planned operation. Conclusion: The diagnosis of endometriosis negatively affects the fertility of women. For some patients, the solution is fertility preservation by cryopreservation methods. Further clinical studies are needed to define exact, practically applicable indication criteria, potential risks of procedures and their benefits and cost-effectiveness.
- MeSH
- fertilita * účinky léků účinky záření MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- protinádorové látky * škodlivé účinky MeSH
- zachování plodnosti metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH