Impact of varicocele repair on semen parameters in infertile men: A systematic review and meta-analysis

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I2=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I2=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I2=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I2=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I2=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I2=89.7%). Conclusions: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies’ practice recommendations favoring VR to improve conventional semen parameters in infertile men

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis

Purpose:Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls.Materials and Methods:A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies).Results:A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; pConclusions:This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.</p

Correlation between seminal plasma levels of GH, IGF-1 and male infertility

Η υπογονιμότητα είναι ένα σύνηθες πρόβλημα που αφορά ένα σημαντικό ποσοστό του παγκόσμιου ανδρικού πληθυσμού και αποτελεί ερευνητικό τομέα εδώ και αρκετές δεκαετίες. Η αυξητική ορμόνη και ο Insulin-like Growth Factor-1 έχουν προταθεί ως παράγοντες που διαδραματίζουν καθοριστικό ρόλο στην ανδρική υπογονιμότητα εξαιτίας της αναβολικής δράσης τους. Ο σκοπός της παρούσας μελέτης είναι η διερεύνηση πιθανής συσχέτισης μεταξύ των επιπέδων GH και IGF-1 του σπερματικού πλάσματος και των σπερματικών παραμέτρεων που πιθανώς επηρεάζουν την ανδρική υπογονιμότητα. H μελέτη πραγματοποιήθηκε μεταξύ Μαΐου 2017 και Σεπτεμβρίου 2017 με τη συμμετοχή 50 ασθενών. Μια οριακά μη σημαντική στατιστική διαφορά (ρ=0.063) στα επίπεδα της GH βρέθηκε ανάμεσα στο φυσιολογικό και το ασθενοσπερμικό γκρουπ. Μια σταστιστικά σημαντική συσχέτιση (ρ&lt;0.05) βρέθηκε ανάμεσα στα επίπεδα της GH και του IGF-1 στο γκρουπ με ασθενοσπερμία και τουλάχιστον μια ακόμη μη φυσιολογική σπερματική παράμετρο. Η παραπάνω συσχέτιση βρέθηκε και στους ασθενείς με χαμηλή συγκέντρωση σπερματοζωαρίων, χαμηλή ζωτικότητα σπερματοζωαρίων και χαμηλό όγκο σπέρματος. Σύμφωνα με την γνώση μας πρόκειται για ένα καινοτόμο εύρημα που χρειάζεται περαιτέρω έρευνα προκειμένου να διασαφηνιστεί η βιολογική σημασία της συσχέτισης αυτής.Infertility is a common problem affecting a considerable percentage of the male population worldwide and has been a research topic for many decades. Growth Hormone and Insulin-like Growth Factor 1 have been proposed as factors that may have a pivotal role in male infertility due to their anabolic effect. The aim of this study is to investigate a possible correlation between seminal plasma levels of GH and IGF-1 and sperm parameters that may exert an impact on fertility. The study took place between May 2017 and September 2017 with the participation of 50 patients. A marginally non-significant statistic difference (p=0.063) in GH levels has been found between asthenospermic group and normal group. A statistically significant correlation (p&lt;0.05) has been found between levels of GH and IGF-1 in the group with asthenospermia and at least one more abnormal parameter. The above correlation has been found also in patients with low sperm concentration, vitality, volume and abnormal morphology. According to our knowledge this is a novel finding and further studies are required in order to clarify the biological significance of this correlation

Evaluation of oocyte characteristics and their behaviour during ICSI with Z-Score, developmental potential, implantation and live-birth rates

The present study aims to evaluate possible associations between oocyte characteristics, oocyte behavior during ICSI, fertilization potential, Z-score analysis, implantation and live birth. It has already been established that a number of oocyte characteristics have been associated with fertilization potential, implantation and live birth rates. Abnormal oolemma breakage and resistance during ICSI application have been equally related with lower implantation potential. Nonetheless, a consensus on definitive associations has not been reached. It may be possible that this lack of consensus may be attributed to the fact that the majority of studies assess oocyte characteristics as a binary outcome (normal/abnormal). In this study oocyte characteristics are assessed as factorial outcomes, with each factor representing a different morphological finding. A total of 477 patients, yielding 3452 oocytes, were enrolled in this observational single-center study.. Single oocyte and subsequent embryo culture were employed. Oocyte morphological evaluation, ICSI practice, respective oocyte behavior information, and fertilization assessment were performed by the same clinical embryologist. Strictly couples undergoing ICSI and double embryo-transfer were eligible to participate. Advanced maternal age>40, azoospermia and/or oligoasthenozoospermia cases were excluded. Meticulous morphological evaluation of oocyte characteristics and assessment of the oocyte behavior during ICSI was recorded. Implantation rate was provided per patient following an hCG level evaluation 14 days post embryo-transfer. Multinomial logistic regression was employed for the statistical analysis. To eliminate possible multiple associations bias, the Bonferroni correction was employed and the confidence levels were adjusted accordingly. Zona pellucida (ZP) characteristics were mainly associated with oocyte behavior during ICSI (p 40, περιπτώσεις αζωοσπερμίας και / ή ολιγοασθενοζωοσπερμίας αποκλείστηκαν από την μελέτη. Πραγματοποιήθηκε σχολαστική καταγραφή της μορφολογικής αξιολόγησης των χαρακτηριστικών των ωαρίων και αξιολόγηση της συμπεριφοράς των ωαρίων κατά τη διάρκεια του ICSI. Το ποσοστό εμφύτευσης παρέχεται ανά ασθενή μετά από αξιολόγηση των επιπέδων hCG ορού 14 ημέρες μετά τη μεταφορά εμβρύου. Για την στατιστική ανάλυση χρησιμοποιήθηκε πολυώνυμη λογιστική παλινδρόμηση. Για την εξάλειψη πιθανού στατιστικού σφάλματος λόγω πολλαπλών συσχετίσεων, χρησιμοποιήθηκε η διόρθωση Bonferroni και τα επίπεδα εμπιστοσύνης προσαρμόστηκαν ανάλογα.Το μη φυσιολογικό πάχος της διάφανης ζώνης σχετίζεται με την απότομη ρήξη της κυτταρικής μεμβράνης (ΚΜ) και την αποτυχία γονιμοποίησης. Τα μη-φυσιολογικά χαρακτηριστικά του ωοπλάσματος συσχετίζονται με μη-φυσιολογική συμπεριφορά κατά την ICSI, κακή ποιότητα ζυγωτού, ενώ η κοκκώδης υφή του κυτταροπλάσματος με την αποτυχία γονιμοποίησης. Το μεγάλο μέγεθος ωαρίου σχετίστηκε με υψηλή αντίσταση κατά την ICSI. Ο μεγάλος διαμεμβρανικός χώρος σχετίζεται με μη φυσιολογική ρήξη της ΚΜ, ενώ η κοκκώδης υφή του συνδέεται με υψηλή αντίσταση κατά την ICSI. Η μη-φυσιολογική συμπεριφορά του ωαρίου κατά την ICSI σχετίζεται με κακή ποιότητα ζυγωτών και με αποτυχία γονιμοποίησης. Μόνο η ξαφνική ρήξη της ΚΜ σχετίστηκε με το ποσοστό γέννησης ζώντων νεογνών.Ορισμένα μη φυσιολογικά χαρακτηριστικά των ωαρίων σχετίζονται με αποκλίσεις από τη φυσιολογική συμπεριφορά των ωαρίων κατά τη διάρκεια του ICSI, θέτοντας άμεσα ή έμμεσα σε κίνδυνο το σχηματισμό ζυγωτών, το Z-Score, την εμφύτευση και το ποσοστό γεννήσεων ζώντων νεογνών. Η χρήση της διόρθωσης κατά Bonferroni οδήγησε στο να αγνοηθεί ένας αριθμός συσχετίσεων που μπορεί να ήταν στατιστικά σημαντικές εάν το μέγεθος του δείγματος ήταν μεγαλύτερο. Το μέτριο μέγεθος του δείγματος, η μεταφορά δυο εμβρύων, μαζί με το γεγονός ότι η μελέτη πραγματοποιήθηκε σε ένα μόνο κέντρο αποτελούν περιορισμούς σε αυτήν τη μελέτη. Η αξιολόγηση των χαρακτηριστικών των ωαρίων και της συμπεριφοράς τους κατά τη διάρκεια του ICSI μπορεί να παρέχει πρώιμες πληροφορίες σχετικά με το αποτέλεσμα του κύκλου. Στην εποχή της ιατρικής ακριβείας, η συμβολή πληροφοριών σχετικά με αυτούς τους συσχετισμούς για την ανάπτυξη ενός συστήματος βαθμολόγησης ή ενός προβλεπτικού μοντέλου μπορεί να βοηθήσει στη διασφάλιση της βέλτιστης πρακτικής και στην ενίσχυση των θετικών αποτελεσμάτων της εξωσωματικής γονιμοποίησης

Abnormal fertilization in ICSI and its association with abnormal semen parameters: a retrospective observational study on 1855 cases

Intracytoplasmic sperm injection (ICSI) efficiently addresses male factor infertility. However, the occurrence of abnormal fertilization, mainly characterized by abnormal pronuclei (PN) patterns, merits investigation. To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis (SA), a retrospective observational study including 1855 cycles was performed. Male infertility diagnosis relied on the 2010 WHO criteria. The population was divided into groups based on their SA results. The presence of 2PNs and extrusion of the second polar body (PB) indicated normal fertilization. A Kruskal-Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups. For the pregnancy rate, logistic regression was employed. No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates. The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups, respectively. The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups. The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates. For the clinical pregnancy rate, no statistically significant difference was observed. In conclusion, the incidence of two or more abnormal SA parameters - with the common denominator being oligozoospermia - may jeopardize normal fertilization, cleavage, and blastocyst rates. Once the developmental milestone of achieving blastocyst stage status was achieved, only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates. Interestingly, following adjustment for the number of blastocysts, no statistically significant differences were observed

Assessing Clinical Embryology Research: A Global Bibliometric Analysis

Background and Objectives: The evaluative strength of available bibliometric tools in the field of clinical embryology has never been examined in the literature. The aim is to bring insight regarding the identity of clinical embryology research, introducing concerns when solely relying on the methodology of bibliometric analysis. Materials and Methods: An all-inclusive analysis of the most bibliometrically highlighted scientific contributions regarding the cornerstones of clinical embryology was performed employing the Scopus, Web of Science (WoS) and PubMed databases, between 1978–2018. An analysis of the number of publications, respective citations and h-index, g-index, along with m-quotient is presented. The top 30 contributing authors for each distinctive area of research are listed. An attempt at visualizing the yearly published articles, clusters, and collaborations of authors, along with the geographic origin of publications, is also presented. Results: Combining all searches and keywords yielded 54,522 results. In the Scopus database, employing the keyword “In Vitro Fertilization” yielded 41,292 results. The publications of the top five authors in each research field were analytically presented and compared to the total number of publications for each respective field. The research field of Preimplantation Genetic Diagnosis/Screening/Testing was allocated the highest percentage of publications produced by the top five authors. Regarding journal bibliometrics, based on the year 2017 metrics, there are only 29 journals according to WoS that refer to “Reproductive Biology”, ranking it 187th among 235 disciplines. The USA produced the highest number of publications (12,537). Conclusion: Results indicate an explosion of interest published in the literature regarding the field of clinical embryology. Further analysis on collaborations and the trends involved should be of added value as productivity between countries varies significantly. This may guide researchers, in vitro fertilization professionals, and prospective authors during literature search, while proving useful regarding manuscript design and concurring on keywords and abstract content

The Impact of the Economic Recession in Greece on Assisted Reproduction Demand: A Retrospective Longitudinal Study

Background and objectives: Since 2009, the decline of the Greek economy has been in the spotlight of the world’s financial agenda. This study assesses the economic crisis’ impact on assisted reproduction demand dynamics. Materials and Methods: Patient records were recruited between 2005–2017. In 2013 the clinic proceeded with a cost reduction. The studied time-frames were defined accordingly: Period A: Prior to economic crisis, Period B: During the economic crisis-prior to cost reduction, and Period C: During the economic crisis-following cost reduction. Analysis focused on parameters reflecting on patient characteristics, decision to inquire on IVF treatment, embarking on it, and proceeding with multiple cycles. Results: The mean annual number of first visit patients was significantly decreased during Period B (1467.00 ± 119.21) in comparison to period A (1644.40 ± 42.57) and C (1637.8 ± 77.23). Furthermore, Period C in comparison to B and A, refers to women of more advanced age (37.27 ± 5.62 vs 36.04 ± 5.76 vs 35.53 ± 5.28), reporting a longer infertility period (8.49 ± 6.25 vs 7.01 ± 5.66 vs 6.46 ± 5.20), being inclined to abandon IVF treatment sooner (2.78 ± 2.51 vs 2.60 ± 1.92 vs 4.91 ± 2.28). Conclusions: A decline regarding assisted reproduction techniques (ART) demand was noted as anticipated. Redefining the cost of infertility treatments may contribute towards overcoming the troubling phenomenon of postponing pregnancy due to financial concerns

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

Recurrent implantation failure (RIF) is a multifactorial condition affecting 10–15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients

Treating infertility: current affairs of cross-border reproductive care

Infertility patients are willing to travel abroad to receive the medical treatment of choice. A 2010 study reported that approximately 25,000 couples travel abroad annually seeking infertility treatment. The purpose of this review is to analyze the criteria and risks related to cross-border reproductive care (CBRC) from the perspective of the patients and explore the issues raised regarding the country of origin and the destination country. A computerized search was performed in PubMed employing respective keywords. The total number of published articles provided by our PubMed search was 1905. Criteria for selecting the destination country include: the economic status, legislation, quality of care and anonymity. Despite the fact that CBRC is becoming a familiar concept, it raises concerns for the practitioner and issues of a social and bioethical nature. Most of them stem from the fact that health care acquires a commercialization aspect. Medical tourism entails several risks, such as misconceptions regarding the destination country, and legal issues arising from differences in the judiciary systems. Larger studies evaluating all aspects of CBRC are imperative. Quality assurance, a consensus and a common platform of practice, along with a system of international governance based on human rights, are a necessity for CBRC patients

Investigating the Role of the microRNA-34/449 Family in Male Infertility: A Critical Analysis and Review of the Literature

There is a great body of evidence suggesting that in both humans and animal models the microRNA-34/449 (miR-34/449) family plays a crucial role for normal testicular functionality as well as for successful spermatogenesis, regulating spermatozoa maturation and functionality. This review and critical analysis aims to summarize the potential mechanisms via which miR-34/449 dysregulation could lead to male infertility. Existing data indicate that miR-34/449 family members regulate ciliogenesis in the efferent ductules epithelium. Upon miR-34/449 dysregulation, ciliogenesis in the efferent ductules is significantly impaired, leading to sperm aggregation and agglutination as well as to defective reabsorption of the seminiferous tubular fluids. These events in turn cause obstruction of the efferent ductules and thus accumulation of the tubular fluids resulting to high hydrostatic pressure into the testis. High hydrostatic pressure progressively leads to testicular dysfunction as well as to spermatogenic failure and finally to male infertility, which could range from severe oligoasthenozoospermia to azoospermia. In addition, miR-34/449 family members act as significant regulators of spermatogenesis with an essential role in controlling expression patterns of several spermatogenesis-related proteins. It is demonstrated that these microRNAs are meiotic specific microRNAs as their expression is relatively higher at the initiation of meiotic divisions during spermatogenesis. Moreover, data indicate that these molecules are essential for proper formation as well as for proper function of spermatozoa per se. MicroRNA-34/449 family seems to exert significant anti-oxidant and anti-apoptotic properties and thus contribute to testicular homeostatic regulation. Considering the clinical significance of these microRNAs, data indicate that the altered expression of the miR-34/449 family members is strongly associated with several aspects of male infertility. Most importantly, miR-34/449 levels in spermatozoa, in testicular tissues as well as in seminal plasma seem to be directly associated with severity of male infertility, indicating that these microRNAs could serve as potential sensitive biomarkers for an accurate individualized differential diagnosis, as well as for the assessment of the severity of male factor infertility. In conclusion, dysregulation of miR-34/449 family detrimentally affects male reproductive potential, impairing both testicular functionality as well as spermatogenesis. Future studies are needed to verify these conclusions