-
Experimental and Clinical... Mar 2023This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess... (Meta-Analysis)
Meta-Analysis Review
This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess the therapeutic effectiveness of stem cell transplant, using different transplant methods, injection sites, and stem cell types, and the reliability of this approach in different animal species. PubMed, the Cochrane Library, and Embase were searched for studies published from January 2006 to February 2022 that evaluated the use of stem cell transplant to treat azoospermia. We included 18 studies and conducted the analyses using Review Manager 5.2 software. Expression of the meiosis-related genes Vasa, Scp3, and Dazl and the average hematoxylin and eosin- positive staining area were improved after stem cell transplant. Subgroup analyses by mode of transplant showed higher expression of Scp3 and Dazl in the xenotransplant group. Although subgroup analyses by injection site showed that the seminiferous tubule group showed the most significant effect on Scp3 expression, spermatogenesis and repair of damaged testis were induced in the tunica albuginea group. The testicular torsion group also induced high levels of Scp3. Another subgroup analysis by stem cell type showed that umbilical cord mesenchymal stem cells promoted the highest expression of meiosis-related genes and successfully induced spermatogenesis and the repair of damaged testis. Urine-derived stem cells, spermatogonial stem cells, and amniotic fluid-derived stem cells showed significantly therapeutic effects; however, more studies are needed for definitive conclusions. Subgroup analyses by type of azoospermia animal model indicated that the use of stem cell transplant in rat or mouse models had an obvious therapeutic effect, but no significant therapeutic effect was seen in azoospermia hamsters. The meta-analysis confirmed that stem cell transplant can effectively treat azoospermia in animal models. Xenotransplant is shown to enhance the therapeutic effects of stem cell transplant on azoospermia.
Topics: Humans; Mice; Male; Rats; Animals; Azoospermia; Reproducibility of Results; Testis; Spermatogenesis; Meiosis
PubMed: 36987796
DOI: 10.6002/ect.2022.0327 -
Andrologia Nov 2020Nonylphenol (NP) is known as an environmental pollutant that has adverse effects on the spermatogenesis process. In this review, we focus on (1999-2020) studies on the... (Review)
Review
Nonylphenol (NP) is known as an environmental pollutant that has adverse effects on the spermatogenesis process. In this review, we focus on (1999-2020) studies on the effect of this pollutant on the sperm parameters and the male reproductive system. Spermatogenesis is a process in which male spermatogonia (primary germ cells) is divided into meiosis and produce spermatozoa. NP and its isomers can cause oxidative stress and alter the production of sex hormones, and thereby disrupting this vital process. By searching in the scientific databases of PubMed, Google Scholar, Science Direct, Springer and Web of Science related articles were extracted. As a result, all observations have confirmed that NP can cause multiple damages to the spermatogenesis and male reproductive system.
Topics: Humans; Male; Phenols; Spermatogenesis; Spermatozoa; Testis
PubMed: 32662580
DOI: 10.1111/and.13748 -
Cytogenetic and Genome Research 2015Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of... (Review)
Review
Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of this study was to provide an overview of sSMC frequency and characterization in a context of infertility and to review the literature describing sSMC in relation with male and female infertility. Therefore, a systematic literature review on sSMC associated with infertility was conducted by means of a PubMed literature and a sSMC database (http://ssmc-tl.com/sSMC.html) search. A total of 234 patients with infertility were identified as carriers of sSMC. All chromosomes, except chromosomes 10, 19 and the X, were involved in sSMC, and in 72% the sSMC originated from acrocentric chromosomes. Euchromatic imbalances were caused by the presence of sSMC in 30% of the cases. Putative genes have been identified in only 1.2% of sSMC associated with infertility. The implication of sSMC in infertility could be due to a partial trisomy of some genes but also to mechanical effects perturbing meiosis. Further precise molecular and interphase-architecture studies on sSMC are needed in the future to characterize the relationship between this chromosomal anomaly and human infertility.
Topics: Adult; Chromosome Aberrations; Chromosome Disorders; Female; Genetic Predisposition to Disease; Humans; Infertility, Female; Infertility, Male; Inheritance Patterns; Male
PubMed: 26398339
DOI: 10.1159/000438718 -
Journal of Gynecology Obstetrics and... Oct 2021In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle.
EVIDENCE REVIEW
A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved.
RESULTS
A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I of over 50 %, indicating substantial heterogeneity between studies.
CONCLUSION(S)
Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.
Topics: Adult; Cryopreservation; Female; Fertility Preservation; Humans; Neoplasms; Ovulation Induction; Pregnancy
PubMed: 33545413
DOI: 10.1016/j.jogoh.2021.102080 -
Theriogenology Sep 2022Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding...
Role of phosphoinositide 3-kinase/ protein kinase B/ phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway inhibitors during in vitro maturation of mammalian oocytes on in vitro embryo production: A systematic review.
Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding of its regulation can be a powerful tool for better in vitro blastocyst production. This systematic review aims to map the evidence of PI3K/AKT/PTEN pathway modulation during in vitro maturation (IVM), to assess its effects on meiosis resumption and nuclear maturation progression of mammalian oocytes, and their impacts on embryo development and quality. A total of 1058 articles were screened in three databases, and 22 articles were included. Fifty-two IVM assessments were identified, among which 11 evaluated blastocyst yield. Three PI3K inhibitors (3-methyladenine, Wortmannin, and LY294002) and one AKT inhibitor (SH6) were investigated. The impact of this pathway modulation on meiosis resumption in swines and murines was not well established, depending on the inhibitor used, concentration, and media supplementation, while in bovines, resumption seems to be independent of PI3K/AKT/PTEN pathway. However, progression to metaphase II (MII) is highly controlled by this pathway on both bovines and swines. Studies that focused on the inhibition reversibility showed that the removal of the modulator produced MII rates similar to the control group. Experiments that aimed to temporarily block meiosis resumption or reduce PI3K activity resulted in blastocyst production equal to or even higher than control groups. Altogether, these data indicate the paramount potential of this pathway as a possible strategy to improve overall in vitro embryo production efficiency, by synchronizing both nuclear and cytoplasmic maturation.
Topics: Animals; In Vitro Oocyte Maturation Techniques; Mammals; Meiosis; Oocytes; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phosphoric Monoester Hydrolases; Proto-Oncogene Proteins c-akt; Tensins
PubMed: 35724451
DOI: 10.1016/j.theriogenology.2022.06.009 -
Reproductive Biology and Endocrinology... Jun 2021Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation.
METHODS
This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle.
RESULTS
A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I = 0%, low evidence).
CONCLUSION
Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger.
TRIAL REGISTRATION
CRD42020204452 .
Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Embryo Implantation; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Maintenance; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 34059045
DOI: 10.1186/s12958-021-00766-5 -
Clinical Genetics Mar 2021Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3.... (Meta-Analysis)
Meta-Analysis
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3. Anticipation and worsening of clinical picture in subsequent generations were repeatedly reported, but there is no indication that SCA3/MJD frequency is changing. Thus, we performed a systematic review and meta-analysis on phenomena with potential effect on SCA3/MJD recurrency in populations: instability of CAG repeat transmissions, anticipation, fitness, and segregation of alleles. Transmission of the mutant allele was associated with an increase of 1.23 CAG repeats in the next generation, and the average change in age at onset showed an anticipation of 7.75 years per generation; but biased recruitments cannot be ruled out. Affected SCA3/MJD individuals had 45% more children than related controls. Transmissions from SCA3/MJD carriers showed that the expanded allele was segregated in 64% of their children. In contrast, transmissions from normal subjects showed that the minor allele was segregated in 54%. The present meta-analysis concluded that there is a segregation distortion favoring the expanded allele, among children of carriers. Therefore, further studies on transmissions and anticipation phenomena as well as more observations about fertility are required to clarify these selective forces over SCA3/MJD.
Topics: Age of Onset; Alleles; Ataxin-3; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Heterozygote; Humans; Machado-Joseph Disease; Meiosis; Recurrence; Trinucleotide Repeat Expansion
PubMed: 33219521
DOI: 10.1111/cge.13888 -
Asian Pacific Journal of Cancer... Oct 2017Background: Numerous similarities have been noted between gametogenic and tumorigenic programs in features such as global hypomethylation, immune evasion,...
Background: Numerous similarities have been noted between gametogenic and tumorigenic programs in features such as global hypomethylation, immune evasion, immortalization, meiosis induction, and migration. In addition, aberrant expression of testis specific genes has been detected in various cancers which has led to categorization of these genes as “cancer-testis genes”. Most of the examples identified in this category are protein encoding. However, recent studies have revealed that non-coding RNAs, including long non coding RNAs (lncRNAs), may have essential regulatory roles in telomere biology, chromatin dynamics, modulation of gene expression and genome structural organization. All of these functions are implicated in both gametogenic and tumorigenic programs. Methods: In the present study, we conducted a computerized search of the MEDLINE/PUBMED and Embase databases with the key words lncRNA, gametogenesis, testis and cancer. Results: We found a number of lncRNAs with essential roles and notable expression in both gametogenic and cancer tissues. Conclusions: Comparison between cancer tissues and gametogenic tissues has shown that numerous lncRNAs are expressed in both, playing similar roles in processes modulated by signaling pathways such as Wnt/β-catenin and PI3K/AKT/mTOR. Evaluation of expression patterns and functions of these genes should pave the way to discovery of biomarkers for early detection, prognostic assessment and evaluation of therapeutic responses in cancers.
PubMed: 29072050
DOI: 10.22034/APJCP.2017.18.10.2601 -
Human Reproduction Update 2016ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly... (Review)
Review
BACKGROUND
ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
METHODS
This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
RESULTS
More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
CONCLUSIONS
This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Topics: Asthenozoospermia; DNA Fragmentation; Female; Fertilization; Humans; Male; Metaphase; Microinjections; Oocytes; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 26586241
DOI: 10.1093/humupd/dmv050 -
Theriogenology Aug 2022Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation. The system uses cAMP modulators in two steps (pre IVM...
Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation. The system uses cAMP modulators in two steps (pre IVM and IVM) and has presented promising results that are arousing the curiosity of IVF programs in different animal species, generating several papers, adaptations, and controversies worldwide. This study systematically analyses the data in the literature on the use of SPOM and compares the outcomes to the original paper (Albuz et al. Hum. Rep., 25: 2999-3011 2010), classifying them into success or failure. The PubMed, Scopus, and Google Scholar databases were searched and 22 studies were included, from which data on 26 experiments were extracted and evaluated via descriptive statistical analysis. Only experiments that assessed the blastocyst rate (BR) were considered for the success parameter, i.e. success (increase in BR) or failure (either no difference or a reduction in BR). The experiments applied the SPOM system in the following species: cattle, sheep, goats, mice, mares and cats. Three experiments (3/26) could not be evaluated for success or failure, and of the remaining, 34.7% (8/23) succeeded in improving blastocyst production. More than two-thirds (69.2%, 18/26) of experiments were conducted in cattle; of those, 86.8% (13/15) used TCM-199 as the IVM media, and 22.2% did not use forskolin or IBMX modulators as indicated in the original study. Also, 27.7% (5/18) of the experiments in cattle used the same type and dose of FSH, and 22% (4/18) used the same protein source and concentration as indicated in the original study. All experiments conducted in mice (3) kept the parameters of the original study in terms of forskolin and IBMX doses and BSA and FSH concentrations, however, they removed cilostamide from IVM. Cilostamide was used during IVM in more than half (53.8%) of all experiments, but only in cattle and sheep. Considering oocyte and embryo assessments, six experiments assessed cAMP levels and most (5/6) of these observed an increase: in cattle (2), sheep (2), and mice (1). Ten experiments evaluated the effect of SPOM on nuclear maturation, and in 90% (9/10), the SPOM system was able to arrest meiosis (cattle, sheep and mice). Thirteen experiments evaluated the total cell number (cattle, mice and sheep), and six (6/13) showed an increase. Our findings clearly indicate difficulties in reproducing the SPOM system worldwide, demonstrating that the meiosis arrest is not sufficient to ensure successful SPOM application. They also suggest that the different supplements used in the IVM medium and/or their interaction with modulators for different durations may produce a significant bias that affects experimental success.
Topics: 1-Methyl-3-isobutylxanthine; Animals; Cattle; Colforsin; Female; Follicle Stimulating Hormone; Horses; In Vitro Oocyte Maturation Techniques; Mice; Oocytes; Sheep
PubMed: 35688043
DOI: 10.1016/j.theriogenology.2022.05.023