reproductive shift
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Úvod a cíl studie: Uterinní NK (uNK) buňky jsou specializovanou subpopulací NK (natural killer) lymfocytů nacházejících se v endometriu. Hrají klíčovou roli v regulaci imunitní odpovědi a v procesu implantace embrya. Cílem této studie je retrospektivní analýza výsledků léčby metodou in vitro fertilizace (IVF) v souboru žen, které podstoupily imunofenotypizaci uNK buněk a na základě výsledků tohoto vyšetření byly, nebo nebyly léčeny imunomodulační terapií. Metody: Studie zahrnovala 122 pacientek, které podstoupily imunofenotypizaci uNK buněk v období od dubna do prosince 2023. Imunofenotypizace byla provedena metodou průtokové cytometrie. Pacientky byly roztříděny do čtyř skupin dle fenotypu uNK buněk: normální nálezy, nízké absolutní a relativní počty uNK (LOW-IMMUNE profil), nízké počty uNK v kombinaci s nežádoucím posunem směrem k cytotoxickému uNKdim imunofenotypu (MIXED-IMMUNE profil) a normální počty uNK, ale nežádoucí posun v poměru cytotoxických a regulačních uNK s cytotoxickým fenotypem (OVER-IMMUNE profil). Byly hodnoceny výsledky embryotransferu a výskyt potratů do ukončeného 12. týdne těhotenství v jednotlivých skupinách. Výsledky: Nejvyšší míra dosažení klinické gravidity byla nalezena v léčené skupině OVER- -IMMUNE (70 %), následované skupinou MIXED-IMMUNE (60 %). Skupina LOW-IMMUNE se od neléčené NORMAL skupiny signifikantně nelišila (p = 0,205). Nedostatečná imunitní aktivace (LOW-IMMUNE profil) byla signifikantně nejčastěji sdružena s prvotrimestrální těhotenskou ztrátou (p < 0,0001). Závěr: Tato studie přináší nové poznatky o potenciálu imunofenotypizace uNK buněk a následné imunomodulační terapie v léčbě poruch plodnosti. Ačkoli výsledky naznačují možné klinické přínosy, je zapotřebí dalšího výzkumu k potvrzení těchto zjištění a k objasnění mechanizmů, které vedou ke zlepšení výsledků léčby technikami asistované reprodukce.
Introduction and objective: Uterine NK (uNK) cells, a specialized subpopulation of natural killer (NK) lymphocytes located in the endometrium, play a crucial role in regulating the immune response and in the process of embryo implantation. This study aims to retrospectively analyze the outcomes of in vitro fertilization (IVF) treatment in a cohort of women who underwent uNK cell immunophenotyping with subsequent immunomodulatory therapy applied based on the results. Methods: The study included 122 patients who underwent uNK cell immunophenotyping between April and December 2023. Immunophenotyping was performed using flow cytometry. Patients were categorized into four groups according to their uNK cell phenotypes: normal findings, low absolute and relative numbers of uNK cells (LOW-IMMUNE profile), low numbers of uNK cells combined with the shift towards the cytotoxic uNKc dim immunophenotype (MIXED-IMMUNE profile), and normal numbers of uNK cells, but an undesirable shift in the ratio of cytotoxic to regulatory uNK cells towards the cytotoxic uNK dim phenotype (OVER-IMMUNE profile). Embryo transfer outcomes and the occurrence of miscarriages up to the 12th week of pregnancy were evaluated in each group. Results: The highest clinical pregnancy rate was observed in the treated OVER-IMMUNE group (70%), fol lowed by the MIXED-IMMUNE group (60%). The LOW-IMMUNE group did not differ significantly from the untreated NORMAL group (P = 0.205). Insufficient immune activation (LOW-IMMUNE profile) was significantly associated with first-trimester pregnancy loss (P < 0.0001). Conclusion: This study provides new insights into the potential benefits of uNK cell immunophenotyping and subsequent immunomodulatory therapy in treating fertility disorders. While the results indicate possible clinical advantages, further research is necessary to confirm these findings and elucidate the mechanisms leading to improved outcomes in assisted reproductive techniques.
- Klíčová slova
- uterinní NK buňky, imunofenotypizace lymfocytů, opakované selhání implantace,
- MeSH
- buňky NK MeSH
- endometrium cytologie MeSH
- fertilizace in vitro * MeSH
- habituální potrat MeSH
- imunofenotypizace MeSH
- imunomodulace MeSH
- lidé MeSH
- průtoková cytometrie metody MeSH
- retrospektivní studie MeSH
- ženská infertilita * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol). The changes were assessed using steroid levels and steroid molar ratios (SMRs) that may reflect the activities of steroidogenic enzymes (SMRs). A repeated measures ANOVA, followed by multiple comparisons and OPLS models, were used for statistical analyses. The anti-MS treatment decreased steroid levels in the follicular phase. Anti-CD20 monoclonal antibodies (mAb), such as ofatumumab and ocrelizumab; inhibitors of the sphingosine-1-phosphate receptor (S1PRI); and IFNβ-1a decreased circulating 17-hydroxy-pregnanes and shifted the CYP17A1 functioning from the hydroxylase- toward the lyase step. Decreased conjugated/unconjugated steroid ratios were found after treatment with anti-MS drugs, especially for glatiramer acetate and anti-CD20 mAb. In the luteal phase, IFN-β1a treatment increased steroidogenesis; both IFN-β1a and ocrelizumab increased AKR1D1, and S1PRI increased SRD5A functioning. Anti-CD20 mAb reduced the functioning of enzymes catalyzing the synthesis of immunomodulatory 7α/β and 16α-hydroxy-androgens, which may affect the severity of MS. The above findings may be important concerning the alterations in bioactive steroids, such as cortisol; active androgens and estrogens; and neuroactive, neuroprotective, and immunomodulatory steroids in terms of optimization of anti-MS treatment.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- roztroušená skleróza * farmakoterapie metabolismus MeSH
- steroidy terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Given Iran's recent shift towards pronatalist population policies, concerns have arisen regarding the potential increase in abortion rates. This review study examines the trends of (medical), intentional (illegal), and spontaneous abortions in Iran over the past two decades, as well as the factors that have contributed to these trends. METHODS: This paper reviewed research articles published between 2005 and 2022 on abortion in Iran. The study employed the PRISMA checklist for systematic reviews. Articles were searched from international (Google Scholar, PubMed, Science Direct, and Web of Science) and national databases (Magiran, Medlib, SID). Once the eligibility criteria were applied, 42 records were included from the initial 349 records. RESULTS: Abortion is influenced by a variety of socioeconomic and cultural factors and the availability of family planning services. Factors that contribute to unintended pregnancy include attitudes toward abortion, knowledge about reproductive health, access to reproductive health services, and fertility desires, among others. In addition to health and medical factors, consanguineous marriage plays an important role in spontaneous and therapeutic abortion. A higher number of illegal abortions were reported by women from more privileged socioeconomic classes. In comparison, a higher number of medical and spontaneous abortions were reported by women from less privileged socioeconomic classes. CONCLUSION: Iranian policymakers are concerned about the declining fertility rate and have turned to pronatalist policies. From a demographic standpoint, this seems to be a reasonable approach. However, the new population policies, particularly, the Family Protection and Young Population Law, along with creating limitations in access to reproductive health services and prenatal screening tests as well as stricter abortion law could potentially lead to an increase in various types of abortions and their associated consequences.
- MeSH
- indukovaný potrat * statistika a číselné údaje zákonodárství a právo trendy MeSH
- lidé MeSH
- potrat nezákonný statistika a číselné údaje MeSH
- samovolný potrat epidemiologie MeSH
- socioekonomické faktory MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- Geografické názvy
- Írán MeSH
The fertility gap, which indicates the difference between the planned and actual number of children born, can be explained by the shift in parenthood to older ages and is associated with the non-attainment of one's intended reproductive plans. This paper focuses on the gap in the timing of entry into parenthood, i.e. between the planned and actual age at the birth of the first child. The study is based on data from the Women 2016 survey which re-interviewed women of fertile age from the second wave of the Czech Generations & Gender Survey conducted in 2008. At the population level, the fertility timing gap differs across generations. While for Czech women born between 1966 and 1971 the planned age exceeded the actual observed age by one year, the realisation of fertility occurred two years later than planned for the youngest generation (1983-1990) included in the study. At the individual level, the later-than-planned realisation of fertility was found to be related primarily to partner-related factors.
- MeSH
- dítě MeSH
- fertilita * MeSH
- kojenec MeSH
- lidé MeSH
- populační dynamika MeSH
- těhotenství MeSH
- zdravotnické služby * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The quandary known as the Intracytoplasmic Sperm Injection (ICSI) paradox is found at the juncture of Assisted Reproductive Technology (ART) and 'andrological ignorance' - a term coined to denote the undervalued treatment and comprehension of male infertility. The prevalent use of ICSI as a solution for severe male infertility, despite its potential to propagate genetically defective sperm, consequently posing a threat to progeny health, illuminates this paradox. We posit that the meteoric rise in Industrial Revolution 4.0 (IR 4.0) and Artificial Intelligence (AI) technologies holds the potential for a transformative shift in addressing male infertility, specifically by mitigating the limitations engendered by 'andrological ignorance.' We advocate for the urgent need to transcend andrological ignorance, envisaging AI as a cornerstone in the precise diagnosis and treatment of the root causes of male infertility. This approach also incorporates the identification of potential genetic defects in descendants, the establishment of knowledge platforms dedicated to male reproductive health, and the optimization of therapeutic outcomes. Our hypothesis suggests that the assimilation of AI could streamline ICSI implementation, leading to an overall enhancement in the realm of male fertility treatments. However, it is essential to conduct further investigations to substantiate the efficacy of AI applications in a clinical setting. This article emphasizes the significance of harnessing AI technologies to optimize patient outcomes in the fast-paced domain of reproductive medicine, thereby fostering the well-being of upcoming generations.
- MeSH
- asistovaná reprodukce MeSH
- intracytoplazmatické injekce spermie * MeSH
- lidé MeSH
- mužská infertilita * diagnóza genetika terapie MeSH
- sperma MeSH
- umělá inteligence MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- dopisy MeSH
... Evaluation of Non-Established Methods 111 -- C.2.5 Stem Cells, Human Embryos 116 -- C.3 Assisted Reproduction ... ... 123 -- C.3.1 Conditions for Assisted Reproduction 125 -- C.3.2 Donor Anonymity 127 -- C.3.3 Surplus ... ... Errors 204 -- D.4.3 Deficiencies in Informed Consent 208 -- D.4.4 Deficiencies in Medical Records and Shifting ...
ix, 240 stran ; 24 cm
- MeSH
- právní odpovědnost MeSH
- zákonodárství lékařské MeSH
- Publikační typ
- monografie MeSH
- Geografické názvy
- Česká republika MeSH
- Konspekt
- Právo
- NLK Obory
- právo, zákonodárství
- veřejné zdravotnictví
Iran has witnessed three major reversals of population policies since their inception in the 1960s. In response to a rapid decline in fertility to very low levels, the latest policy shift has led to the development of legislation that aims to encourage marriage and fertility, particularly the "Youthful Population and Protection of the Family" law approved in 2021. This study reviews the changes in population policy and their interrelations with fertility trends, focusing mainly on the shift towards pronatalist policies since 2005, and accompanying restriction of reproductive health and family planning services. Combining international and national sources, we position the new pronatalist drive in the country within the broader trend of government attempts to reverse fertility decline and promote conservative family values. Our study has three main aims. (1) We provide an overview of fertility trends, policy discourses and policy shifts in the context of the changes in the societal and political structures of Iran during the last half a century. (2) We highlight and discuss the most problematic features of the new Family Law, especially the legislation pertaining to maternal and reproductive health, access to abortion and contraception, and incentives supporting earlier marriage and higher fertility. (3) We discuss the likely consequences of the new legislation for maternal and child health and sexual and reproductive rights, for women in general, and the country's socio-economic disparities. As well as violating reproductive rights, the new policy is unlikely to achieve its aim of initiating a sustained rise in fertility in Iran.
- MeSH
- dítě MeSH
- fertilita * MeSH
- lidé MeSH
- reprodukční práva * MeSH
- služby plánování rodičovství MeSH
- těhotenství MeSH
- veřejná politika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Írán MeSH
There are multiple classifications in imaging and surgery of endometriosis and in this article, we offer a review of the main evaluation systems. The International Deep Endometriosis Analysis group consensus is the leading document for ultrasound assessment, while magnetic resonance imaging is guided by the European Society for Urogenital Radiology recommendations on technical protocol. In surgery, the revised American Society for Reproductive Medicine classification is the oldest system, ideally combined with newer classifications, such as Enzian or Endometriosis Fertility Index. Recently, The World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project introduced detailed proforma for clinical and intraoperative findings. There is still no universal consensus, so the initial emphasis should be on the uniform reporting of the disease extent until research clarifies more the correlations between extent, symptoms and progression in order to develop a reliable staging system.Impact StatementWhat is already known on this subject? There have been several reviews of surgical classifications, comparing their scope and practical use, while in the imaging the attempts for literature review has been scarce.What do the results of this study add? This is the first up to date review offering detailed analysis of the main classification systems across the three main areas involved in endometriosis care - ultrasound, MRI and surgery. The mutual awareness of the radiological classifications for surgeons and vice versa is crucial in an efficient multidisciplinary communication and patient care. On these comparisons we were able to demonstrate the lack of consensus in description of the extent of the disease and even further lack of prognostic features (with the exemption of one surgical system).What are the implications of these findings for clinical practice and/or further research? Future attempts of scientific societies should focus on defining uniform nomenclature for extent description. In the second step the staging classification should encompass prognostic value (risk of disease and symptoms recurrence).
- MeSH
- endometrióza klasifikace MeSH
- gynekologické chirurgické výkony * MeSH
- gynekologie normy MeSH
- konsensus MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- společnosti lékařské MeSH
- stupeň závažnosti nemoci MeSH
- ultrasonografie * MeSH
- určení symptomu metody normy MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Vertebrate meiotic recombination events are concentrated in regions (hotspots) that display open chromatin marks, such as trimethylation of lysines 4 and 36 of histone 3 (H3K4me3 and H3K36me3). Mouse and human PRDM9 proteins catalyze H3K4me3 and H3K36me3 and determine hotspot positions, whereas other vertebrates lacking PRDM9 recombine in regions with chromatin already opened for another function, such as gene promoters. While these other vertebrate species lacking PRDM9 remain fertile, inactivation of the mouse Prdm9 gene, which shifts the hotspots to the functional regions (including promoters), typically causes gross fertility reduction; and the reasons for these species differences are not clear. RESULTS: We introduced Prdm9 deletions into the Rattus norvegicus genome and generated the first rat genome-wide maps of recombination-initiating double-strand break hotspots. Rat strains carrying the same wild-type Prdm9 allele shared 88% hotspots but strains with different Prdm9 alleles only 3%. After Prdm9 deletion, rat hotspots relocated to functional regions, about 40% to positions corresponding to Prdm9-independent mouse hotspots, including promoters. Despite the hotspot relocation and decreased fertility, Prdm9-deficient rats of the SHR/OlaIpcv strain produced healthy offspring. The percentage of normal pachytene spermatocytes in SHR-Prdm9 mutants was almost double than in the PWD male mouse oligospermic sterile mutants. We previously found a correlation between the crossover rate and sperm presence in mouse Prdm9 mutants. The crossover rate of SHR is more similar to sperm-carrying mutant mice, but it did not fully explain the fertility of the SHR mutants. Besides mild meiotic arrests at rat tubular stages IV (mid-pachytene) and XIV (metaphase), we also detected postmeiotic apoptosis of round spermatids. We found delayed meiosis and age-dependent fertility in both sexes of the SHR mutants. CONCLUSIONS: We hypothesize that the relative increased fertility of rat versus mouse Prdm9 mutants could be ascribed to extended duration of meiotic prophase I. While rat PRDM9 shapes meiotic recombination landscapes, it is unnecessary for recombination. We suggest that PRDM9 has additional roles in spermatogenesis and speciation-spermatid development and reproductive age-that may help to explain male-specific hybrid sterility.
- MeSH
- chromatin MeSH
- dvouřetězcové zlomy DNA MeSH
- fertilita genetika MeSH
- histonlysin-N-methyltransferasa genetika MeSH
- krysa rodu rattus MeSH
- meióza * genetika MeSH
- myši MeSH
- potkani inbrední SHR MeSH
- spermatogeneze genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
MEHMO syndrome is a rare X-linked syndrome characterized by Mental retardation, Epilepsy, Hypogenitalism, Microcephaly, and Obesity associated with the defect of protein synthesis caused by the EIF2S3 gene mutations. We hypothesized that the defect in protein synthesis could have an impact on the immune system. We describe immunologic phenotype and possible treatment outcomes in patient with MEHMO syndrome carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. The proband (currently 9-year-old boy) had normal IgG and IgM levels, but had frequent respiratory and urinary tract infections. On subcutaneous immunoglobulin therapy achieving supra-physiological IgG levels the frequency of infections significantly decreased in Poisson regression by 54.5 % (CI 33.2-89.7, p=0.017). The MEHMO patient had had frequent acute infections despite normal IgG and IgM serum levels and responded well to the immunoglobulin treatment.
- MeSH
- dítě MeSH
- epilepsie farmakoterapie genetika imunologie patologie MeSH
- eukaryotický iniciační faktor 2 genetika MeSH
- fenotyp MeSH
- hypogonadismus farmakoterapie genetika imunologie patologie MeSH
- lidé MeSH
- mentální retardace vázaná na chromozom X farmakoterapie genetika imunologie patologie MeSH
- mikrocefalie farmakoterapie genetika imunologie patologie MeSH
- mutace * MeSH
- obezita farmakoterapie genetika imunologie patologie MeSH
- pohlavní orgány abnormality imunologie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH