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
Cíl: V současné době rychle přibývá nových studií o asistované aktivaci oocytů, která může výrazně zefektivnit celý proces in vitro fertilizace. Oplození oocytů konvenční metodou i pomocí intracytoplazmatické injekce spermie může selhat z důvodu nedostatečné aktivace oocytu. Důvodem bývají zejména odchylky v enzymovém vybavení spermií nebo oocytů či nefunkční aktivační kaskáda. V řadě případů lze oplození dosáhnout užitím umělé aktivace oocytů pomocí aplikace donorů vápníkových iontů na oocyty po mikroinjekci spermie. Názory na bezpečnost a spolehlivost této metody však nejsou jednotné. Cílem práce je prezentovat současné poznatky o asistované aktivaci oocytů a o jejím dopadu nejen na in vitro fertilizaci, ale také na následný embryonální a fetální vývoj. Metodika: Rešerše relevantní literatury v databázích Web of Science, Scopus a PubMed/Medline. Výsledky a závěr: Z literárních údajů i vlastních zkušeností autorů vyplývá, že je tato metoda účinná a z hlediska dalšího vývoje embrya, plodu i postnatálního vývoje bezpečná. Byly provedeny rozsáhlé metaanalýzy zaměřené na tuto metodu, které nezjistily negativní dopad nejen na embryonální a fetální vývoj jedince, ale tato metoda neměla negativní dopad ani na psychosomatický vývoj narozených dětí.
Objective: Currently, there is a rapid increase in studies on assisted oocyte activation, which can significantly improve the process of in vitro fertilization. Fertilization of oocytes by conventional methods and by intracytoplasmic sperm injection can be affected by insufficient activation of the oocyte. The reason is mainly deviations in the enzymatic equipment of sperm or oocytes or a non-functional activation cascade. In many cases, fertilization can be achieved using artificial oocyte activation by applying calcium ion donors to the oocytes after sperm microinjection. However, opinions on the safety and reliability of this method are not uniform. The aim of the thesis is to present current knowledge about assisted oocyte activation and its impact not only on in vitro fertilization, but also on subsequent embryonic and fetal development. Methodology: Research of relevant literature in Web of Science, PubMed/Medline and Scopus databases. Results and conclusions: Based on the literature data and the authors’ own experience, it follows that this method is effective and safe from the point of view of further development of the embryo, fetus and postnatal development. Extensive meta-analyses focused on this method were carried out, which did not find a negative impact not only on the embryonic and fetal development of the individual, but this method did not have associated with a negative impact on the psychosomatic development of the children.
- MeSH
- fertilizace in vitro * metody MeSH
- intracytoplazmatické injekce spermie MeSH
- ionofory kalciové aplikace a dávkování MeSH
- lidé MeSH
- oocyty * fyziologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
The aim of this study was to evaluate the efficiency of using meiotic spindle (MS) visibility and relative position to the polar body (PB) as indicators of oocyte maturation in order to optimize intracytoplasmic sperm injection (ICSI) timing. This was a cohort study of patients younger than 40 years with planned ICSI, the timing of which was determined by MS status, compared with those without MS evaluation. The angle between PB and MS and MS visibility were evaluated by optical microscope with polarizing filter. Oocytes with MS evaluation were fertilized according to MS status either 5-6 h after ovum pick-up (OPU) or 7-8 h after OPU. Oocytes without MS evaluation were all fertilized 5-6 h after OPU. For patients over 35 years visualization of MS influenced pregnancy rate (PR): 182 patients with MS visualization had 32% PR (58/182); while 195 patients without MS visualization had 24% PR (47/195). For patients under 35 years, visualization of MS did not influence PR: 140 patients with MS visualization had 41% PR (58/140), while 162 patients without MS visualization had 41% PR (66/162). Visualization of MS therefore appears to be a useful parameter for assessment of oocyte maturity and ICSI timing for patients older than 35.
STUDY QUESTION: Does a single oral dose of nolasiban 900 mg administered 4 h before embryo transfer (ET) increase pregnancy rates in women undergoing IVF? SUMMARY ANSWER: In an individual patient data (IPD) meta-analysis of three clinical trials, a single oral dose of nolasiban 900 mg was associated with an increased ongoing pregnancy rate of an absolute 5% (relative 15%). WHAT IS KNOWN ALREADY: Several clinical studies have shown that blocking activation of oxytocin receptors by an oxytocin receptor (OTR) antagonist has the potential to decrease uterine contractions, increase endometrial perfusion and enhance endometrial decidualisation and other parameters of endometrial receptivity. It has been hypothesised that antagonism of oxytocin receptors could improve the likelihood of successful embryo implantation and thus increase pregnancy and live birth rates following ET. STUDY DESIGN, SIZE, DURATION: This is an analysis of three randomised, double-blind, placebo-controlled trials, which randomised 1836 subjects between 2015 and 2019. We describe the results of a meta-analysis of individual participant data (IPD) from all three trials and the pre-specified analyses of each individual trial. PARTICIPANT/MATERIAL, SETTING, METHODS: Participants were patients undergoing ET following IVF/ICSI in 60 fertility centres in 11 European countries. Study subjects were below 38 years old and had no more than one previously failed cycle. They were randomised to a single oral dose of nolasiban 900 mg (n = 846) or placebo (n = 864). In IMPLANT 1, additional participants were also randomised to nolasiban 100 mg (n = 62) or 300 mg (n = 60). Fresh ET of one good quality embryo (except in IMPLANT 1 where transfer of two embryos was allowed) was performed on Day 3 or Day 5 after oocyte retrieval, approximately 4 h after receiving the study treatment. Serum hCG levels were collected at 14 days post oocyte retrieval (Week 2) and for women with a positive hCG result, ultrasound was performed at Week 6 post-ET (clinical pregnancy) and at Week 10 post-ET (ongoing pregnancy). Pregnant patients were followed for maternal (adverse events), obstetric (live birth, gestational age at delivery, type of delivery, incidence of twins) and neonatal (sex, weight, height, head circumference, Apgar scores, congenital anomalies, breast feeding, admission to intensive care and specific morbidities e.g. jaundice, respiratory distress syndrome) outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: In an IPD meta-analysis of the clinical trials, a single oral dose of nolasiban 900 mg was associated with an absolute increase of 5.0% (95% CI 0.5, 9.6) in ongoing pregnancy rate and a corresponding increase of 4.4% (95% CI -0.10, 8.93) in live birth rate compared to placebo. Similar magnitude increases were observed for D3 or D5 transfers but were not significantly different from the placebo. Population pharmacokinetics (PK) demonstrated a correlation between higher exposures and pregnancy. LIMITATIONS, REASON FOR CAUTION: The meta-analysis was not a pre-specified analysis. While the individual trials did not show a consistent significant effect, they were not powered based on an absolute increase of 5% in ongoing pregnancy rate. Only a single dose of up to 900 mg nolasiban was administered in the clinical trials; higher doses or extended regimens have not been tested. Only fresh ET has been assessed in the clinical trials to date. WIDER IMPLICATIONS OF THE FINDINGS: The finding support the hypothesis that oxytocin receptor antagonism at the time of ET can increase pregnancy rates following IVF. The overall clinical and population PK data support future evaluation of higher doses and/or alternate regimens of nolasiban in women undergoing ET following IVF. STUDY FUNDING/COMPETING INTERESTS: The trials were designed, conducted and funded by ObsEva SA. A.H., O.P., E.G., E.L. are employees and stockholders of ObsEva SA. E.L. is a board member of ObsEva SA. G.G. reports honoraria and/or non-financial support from ObsEva, Merck, MSD, Ferring, Abbott, Gedeon-Richter, Theramex, Guerbet, Finox, Biosilu, Preglem and ReprodWissen GmbH. C.B. reports grants and honoraria from ObsEva, Ferring, Abbott, Gedeon Richter and MSD. P.P. reports consulting fees from ObsEva. H.T. reports grants and or fees from ObsEva, Research Fund of Flanders, Cook, MSD, Roche, Gedeon Richter, Abbott, Theramex and Ferring. H.V. reports grants from ObsEva and non-financial support from Ferring. P.T. is an employee of Cytel Inc., who provides statistical services to ObsEva. J.D. reports consulting fees and other payments from ObsEva and, Scientific Advisory Board membership of ObsEva. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02310802, NCT03081208, NCT03758885. TRIAL REGISTRATION DATES: December 2014 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885). FIRST PATIENT’S ENROLMENT: January 2015 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885).
- MeSH
- dospělí MeSH
- fertilizace in vitro MeSH
- intracytoplazmatické injekce spermie * MeSH
- lidé MeSH
- novorozenec MeSH
- oximy MeSH
- oxytocin MeSH
- přenos embrya MeSH
- pyrrolidiny MeSH
- randomizované kontrolované studie jako téma MeSH
- receptory oxytocinu * MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
The most common reason for in vitro fertilization (IVF) cycle cancelation is a lack of quality gametes available for intracytoplasmic sperm injection (ICSI). Here we present the successful fertility treatment of the couple affected by obstructive azoospermia combined with suboptimal response to controlled ovarian stimulation. Since the conventional approach appeared ineffective to overcome both partners' specific problems, the targeted interventions, namely, (1) pharmacological enhancement of sperm motility and (2) polarized light microscopy (PLM)-guided optimization of ICSI time, were applied to rescue the cycle with only immature oocytes and immotile testicular sperm retrieved. The treatment with theophylline aided the selection of viable spermatozoa derived from cryopreserved testicular tissue. When the traditional stimulation protocol failed to produce mature eggs, non-invasive spindle imaging was employed to adjust the sperm injection time to the maturational stage of oocytes extruding a polar body in vitro. The fertilization of 12 late-maturing oocytes yielded 5 zygotes, which all developed into blastocysts. One embryo was transferred into the uterus on day 5 post-fertilization, and another 3 good quality blastocysts were vitrified for later use. The pregnancy resulted in a full-term delivery of a healthy child. This case demonstrates that the individualization beyond the standard IVF protocols should be considered to maximize the chance of poor-prognosis patients to achieve pregnancy with their own gametes.
- MeSH
- azoospermie epidemiologie terapie MeSH
- ejakulace fyziologie MeSH
- fertilizace in vitro trendy MeSH
- indukce ovulace MeSH
- intracytoplazmatické injekce spermie MeSH
- kryoprezervace * MeSH
- lidé MeSH
- motilita spermií genetika MeSH
- narození živého dítěte epidemiologie MeSH
- oocyty růst a vývoj MeSH
- oogeneze genetika MeSH
- spermie patologie transplantace MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
RESEARCH QUESTION: Is individualization of dosing with follitropin delta in sequential ovarian stimulation cycles an effective preventive strategy for ovarian hyperstimulation syndrome risk? If so, for which patients does an individualized strategy provide the greatest OHSS risk reduction and/or the need for additional preventive interventions? DESIGN: A secondary analysis of three ovarian stimulation cycles in IVF/intracytoplasmic sperm injection patients included in one randomized, assessor-blinded trial comparing two recombinant FSH preparations (ESTHER-1, NCT01956110), and a second trial in women undergoing up to two additional cycles (ESTHER-2, NCT01956123). Of 1326 women (aged 18-40 years) randomized and treated with follitropin delta or alfa in cycle 1, 513 continued to cycle 2 and 188 to cycle 3. Follitropin delta and alfa doses were maintained/adjusted according to ovarian response in the previous cycle. RESULTS: Individualized dosing with follitropin delta significantly reduced moderate/severe OHSS and/or preventive interventions (P=0.018) versus conventional dosing with follitropin alfa in patients undergoing up to three ovarian stimulation cycles. The greatest benefit was observed in patients in the highest anti-Müllerian hormone (AMH) quartile (P=0.012). On evaluating separately, individualized dosing with follitropin delta significantly lowered the incidences of moderate/severe OHSS (P=0.036) and preventive interventions (P=0.044) versus follitropin alfa. CONCLUSION: An individualized follitropin delta dosing regimen decreased the risk of moderate/severe OHSS as well as the incidence of preventive interventions versus a conventional follitropin alfa regimen. An analysis per AMH quartile indicated that these statistically significant differences are driven mainly by patients with the highest pretreatment AMH levels.
- MeSH
- dospělí MeSH
- fertilizace in vitro MeSH
- folikuly stimulující hormon lidský aplikace a dávkování terapeutické užití MeSH
- indukce ovulace * škodlivé účinky MeSH
- interpretace statistických dat MeSH
- intracytoplazmatické injekce spermie MeSH
- kryoprezervace MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ovariální hyperstimulační syndrom prevence a kontrola MeSH
- ovarium účinky léků MeSH
- rekombinantní proteiny aplikace a dávkování terapeutické užití MeSH
- riziko MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
The effect of extracellular sperm ubiquitination was examined from many aspects and the majority of existing studies negatively correlated the amount of highly ubiquitinated sperm cells in the sample with the ejaculate quality and the fertilization success rate. In the present study, we compared an early embryonic development up to blastocyst stage in the pig using two defined sperm cell populations sorted by flow cytometry (FACS) based on the rate of the extracellular ubiquitination. This novel approach allows studying the direct effect of extracellular ubiquitin (eUb), which is a marker for epididymal recognition and degradation of defective sperm cells. We further examined the hypothesis that eUb could be recognized directly in the ooplasm. In the porcine model, the significance of results might be seriously affected by a high variability among sperm cell doses from individual boars as well as by the variability among separate sample collections. To overcome this obstacle, we used cryopreserved sperm cells from a single dose. Comparison of an early embryonic development employing intracytoplasmic sperm cell injection (ICSI) with cryopreserved (frozen/thawed, F/T) and fresh sperm cells did not reveal significant difference regarding blastocyst formation rate. We also observed no difference in the male and female pronuclei formation and the first zygote cleavage after fertilization of oocytes with high or non-ubiquitinated sperm cells sorted by FACS. However, results of the early embryonic development to the blastocyst stage showed the difference between both experimental groups (16.67% of blastocysts in non-ubiquitinated group vs. 6.20% of blastocyst in the high-ubiquitinated group, P < 0.001). We further confirmed the negative effect of eUb by the masking of Ub epitopes with the appropriate primary antibody in fresh sperm cells prior to ICSI. This procedure improved the blastocyst formation rate from 14.19% in the untreated group to 24.03% concerning antibody masked sperms (P < 0.01). We conclude our results support a generally accepted hypothesis concerning the negative correlation of the presence of eUb on the sperm cell membrane and developmental competence of fertilized oocytes. However, experiments with masking Ub antibody indicate the direct negative effect of the membrane ubiquitin rather than sperm cell quality on the early embryonic development to the blastocyst stage, at least in the porcine model.
- MeSH
- blastocysta fyziologie MeSH
- intracytoplazmatické injekce spermie veterinární MeSH
- kryoprezervace veterinární MeSH
- kultivace embrya veterinární MeSH
- oocyty fyziologie MeSH
- prasata * MeSH
- průtoková cytometrie MeSH
- spermie fyziologie MeSH
- ubikvitinace fyziologie MeSH
- uchování spermatu veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PROPOSE: The presence of metaphase II (MII) spindle together with the polar body (PB) indicates completion of oocyte maturation. This study was designed to explore if spindle imaging can be used to optimize timing of intracytoplasmic sperm injection (ICSI). METHODS: The study involved 916 oocytes from 234 conventionally stimulated ICSI cycles with an unexpectedly poor ovarian response. All PB-displaying oocytes were subjected to polarized light microscopy (PLM) prior to ICSI. When MII spindle was absent in the majority of oocytes, ICSI was postponed and performed after additional spindle imaging. Fertilization, embryo development, and clinical outcome were evaluated with respect to the observed spindle pattern. RESULTS: The visible spindle was absent in 32.64% of PB-displaying oocytes. The late-maturing oocytes extruding PB in vitro were less likely to exhibit a spindle signal than in vivo matured MII oocytes (38.86% vs. 89.84%). When fertilization was postponed, 59.39% of initially spindle-negative oocytes developed detectable MII spindle. Spindled eggs had significantly higher developmental potential, and the presence of the spindle has been identified as an independent measure for predicting the formation of the blastocyst. Embryos derived from spindle-positive oocytes also showed a higher chance to implant and develop to term. Notably, 11 children were conceived by finely timed fertilization of late-maturing oocytes which are normally discarded. CONCLUSIONS: The study confirms the prognostic value of spindle imaging and demonstrates that immature oocytes can be clinically utilized and give rise to live births when the timing of ICSI is adjusted to their developmental stage.
- MeSH
- embryonální vývoj genetika MeSH
- fertilizace in vitro * MeSH
- intracytoplazmatické injekce spermie * MeSH
- lidé MeSH
- metafáze genetika MeSH
- oocyty růst a vývoj ultrastruktura MeSH
- oogeneze genetika MeSH
- polarizační mikroskopie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- FOLANDROL,
- MeSH
- centrifugace - gradient hustoty metody MeSH
- fertilizace in vitro metody MeSH
- intracytoplazmatické injekce spermie metody MeSH
- lidé MeSH
- magnetismus MeSH
- mužská infertilita komplikace MeSH
- oligospermie farmakoterapie MeSH
- potravní doplňky MeSH
- separace buněk metody MeSH
- spermie cytologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Klíčová slova
- PICSI, IMSI,
- MeSH
- asistovaná reprodukce MeSH
- fertilizace in vitro * metody MeSH
- intracytoplazmatické injekce spermie * metody přístrojové vybavení MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
