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This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

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INTRODUCTION: Microsurgical testicular sperm extraction (microTESE) is crucial for treating non-obstructive azoospermia (NOA), offering both 'fresh' and 'frozen' options. This study evaluates the impact of fresh versus frozen microTESE on the progression to intra-cytoplasmic sperm injection (ICSI) cycles, focusing on sperm motility. MATERIALS AND METHODS: We conducted a retrospective analysis of microTESE procedures at a major medical centre from 2007 to 2021, excluding cases of obstructive azoospermia and cryptozoospermia. Patients were divided into two groups: fresh microTESE (Group FR) and frozen microTESE (Group FZ). Sperm motility was assessed, and ICSI outcomes were compared between groups. RESULTS: Out of 128 microTESE procedures on 113 NOA patients, 31 were fresh and 97 were frozen. Sperm was found in 67.7% of fresh cases and 45.3% of frozen cases. In fresh cases, 85.7% had motile sperm for ICSI, whereas in frozen cases, 81.8% had motile sperm initially, but only 52.7% retained motility post-thaw. CONCLUSIONS: Our findings indicate a significant drop in motile sperm availability for ICSI in frozen microTESE cases compared to fresh ones. This suggests a potential advantage of fresh microTESE for certain couples, despite the logistical challenges, highlighting the need for careful patient selection and counselling.

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Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D. Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane's Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results. Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding. Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.

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Background: The global prevalence of infertility is 9%, with male factors potentially accounting for 40% to 60% of cases. Conventional treatments can be ineffective, invasive, costly, and linked to adverse effects and high risks. Previous studies have shown that, Chinese herbal medicine (CHM) can regulate the hypothalamus-pituitary-testis axis, improve sperm abnormalities and quality, mitigate oxidative stress, and decrease DNA fragmentation index (DFI). Yet, the evidence backing the use of Chinese herbal medicine (CHM) for treating male factor infertility lacks conviction due to study design limitations, and there remains a scarcity of studies on the live birth rate following CHM treatment for male factor infertility. Here, we describe the rationale and design of a randomized waitlist-controlled trial to evaluate the effect of CHM on the live birth rate among males with infertility. Methods: This study is a single-center, randomized, waitlist-controlled study. A total of 250 couples diagnosed with male factor infertility will be enrolled in this study and then randomly allocated into two groups in a 1:1 ratio. Male participants in CHM group (treatment group) will receive CHM once a day for 3 months. Male participants in the waitlist group (control group) will not receive any treatment for 3 months. After 3 months, participants in both groups need to be followed up for another 12 months. The primary outcome will be the live birth rate; secondary outcomes include semen quality parameters, DFI and pregnancy related outcomes. Safety will also be assessed. Discussion: The purpose of this trial is to explore the effects and safety of CHM on the live birth rate among couples dealing with male factor infertility. The outcome of this trial may provide a viable treatment option for male factor infertility. Trial registration: Chinese Clinical Trial Registry: ChiCTR2200064416. Registered on 7 October 2022, https://www.chictr.org.cn.

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Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

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Objective: To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction. Design: Case report. Patients: A single patient diagnosed with nonobstructive azoospermia underwent microdissection testicular sperm extraction, and an incidental finding of invasive seminoma was made upon histopathological analysis. Results: An incidental discovery of invasive seminoma was observed in the sample pathology obtained during the microdissection testicular sperm extraction. Consequently, the patient underwent further diagnostic workup and a radical orchiectomy. Conclusions: Men with male factor infertility are at increased risk of testicular cancer. As such, it is imperative to incorporate a thorough physical examination and relevant imaging into their diagnostic process. Additionally, it is advisable to include histopathological analysis for all individuals undergoing microdissection testicular sperm extraction.

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Couple infertility is a common condition, defined as being unable to conceive after 12 months of regular unprotected sexual intercourse. Male Factor Infertility (MFI) is responsible, alone or in combination with female factors, for about half of the overall cases of couple infertility. MFI is gradually increasing in prevalence, with a notable decline in semen parameters over the last decades. The aetiologies behind the finding of decreasing sperm counts are difficult to pinpoint but might be due in part to increasing rates of overweight and obesity in men of childbearing age. Diabetes mellitus (DM) is a common and chronic metabolic disease, whose prevalence is also gradually increasing, rising up to 10% of the population. The International Diabetes Federation estimates that there are currently more than 500 million people living with DM worldwide, the vast majority of whom suffering from type 2 DM (T2DM). There is growing awareness of the relationship between unhealthy lifestyle, in particular unhealthy diet, and MFI. Starting from all these premises, the aim of this narrative review is to describe the current evidence on the link between DM and MFI, both in terms of DM as a cause of/a risk factor for MFI and of MFI as a possible predictive marker for T2DM. Finally, we will discuss the risk of DM as a consequence of the therapy of MFI or assisted reproductive techniques.

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OBJECTIVE: To study whether severe male factor infertility (SMF), reflected by oligozoospermia, impacts embryo morphokinetic behavior in low-prognosis women as stratified by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. DESIGN: Cohort study. SETTING: Private university-affiliated in vitro fertilization center. PATIENT(S): A total of 10,366 injected oocytes from 2,272 women who underwent intracytoplasmic sperm injection cycles between March 2019 and April 2022. INTERVENTION(S): Patients were divided into 8 groups according to the POSEIDON criteria (1-4) and the presence or absence of SMF. A control group of normoresponder patients was included. Kinetic markers from the point of insemination were recorded in the EmbryoScope incubator. MAIN OUTCOME MEASURE(S): Morphokinetic milestones and intracytoplasmic sperm injection clinical outcomes. RESULT(S): Embryos from patients in the POSEIDON 1 group showed significantly slower timing to pronuclear appearance, timing to pronuclear fading (tPNf), timing to 2 (t2), 3 (t3), 4 (t4), 6 (t6), and 7 (t7) cells than those from the control group. Known Implantation Diagnosis Score ranking was significantly different between the SMF and non-SMF (nSMF) subgroups in both POSEIDON 1 as well as control groups. Embryos from patients in the POSEIDON 2 group showed significantly slower timing to pronuclear appearance, t4, t6, t7, timing to 8 cells (t8), and timing to morulae than those from the control group. Embryos in the POSEIDON 2 SMF subgroup took longer than those in the POSEIDON 2 nSMF subgroup and those in both control subgroups to achieve tPNf, t2, t3, timing to 5 cells (t5), timing to start blastulation, and timing to blastulation. Known Implantation Diagnosis Score ranking was significantly different between the SMF and nSMF subgroups in both POSEIDON 2 as well as control groups. Embryos from patients in the POSEIDON 3 group showed significantly slower t8 and duration of the second cell cycle (t3-t2) than those from the control group. Known Implantation Diagnosis Score ranking was significantly different across the subgroups. Embryos derived from patients in the POSEIDON 4 group showed significantly slower tPNf, t2, t3, t4, t5, t6, t7, t8, timing to complete t4-t3 synchronous divisions, and timing to complete t8-t5 synchronous divisions than those from the control group. Known Implantation Diagnosis Score ranking was significantly different between the SMF and nSMF subgroups in both POSEIDON 4 as well as control groups. Irrespective of sperm quality, clinical outcomes significantly improved in the control subgroups compared with those in the POSEIDON 2 and 4 subgroups. CONCLUSION(S): Embryos in the SMF groups presented lower Known Implantation Diagnosis Score ranking than those in the nSMF groups in both POSEIDON 1-4 and control groups, suggesting that cumulative differences result in worse morphokinetic development when the algorithm is used.

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Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.

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BACKGROUND: Male infertility is the inability of a male to conceive a fertile female during at least a year of unprotected sexual activity. A variety of medical conditions and treatments cause male infertility. Y chromosome microdeletion is an important cause of infertility among males. Various epidemiological factors also play a role in the occurrence of infertility. Our study aims to determine the association between Y-chromosome microdeletion and age, sperm count, body mass index (BMI), alcohol, and tobacco consumption. METHODS: This study was conducted in 70 male infertility cases. Data was collected from 2018 to 2023 at the Genetic Lab, Department of Anatomy, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India. Demographic profiles, including age, sperm count, weight and height, and history of smoking and drinking, were collected from individuals. BMI was calculated, and chromosome analysis was done for Y chromosome microdeletion. Both multiplex and singleplex methods were used to determine the microdeletion using a thermocycler (Applied Biosystems, VeritiTM 96-well Fast Thermal Cycler, 0.2 ml USA) in AZF, and the association between age, sperm count, BMI, alcohol, and tobacco was determined. RESULTS: The number of regions deleted among individuals varies from one to seven. Regions Sy746, Sy143, and Sy145 were found to be commonly deleted. We found a positive, but not statistically significant, correlation between age and microdeletion (point biserial correlation coefficient (r) = 0.2, p-value = 0.097). When comparing age with sperm count, the results showed a negative correlation, highlighting the influence of age on sperm count (r (68) = 0.284, p = 0.017). In comparing BMI and microdeletion, no significant relationship (χ² = 3.7, p = 0.296) indicated independence between them. According to our observations, microdeletion affects all smokers and 45% of non-smokers. We found a significant association between smoking and microdeletion (χ2 = 4.49, P = 0.034). There was no statistically significant relationship between microdeletion and drinking (χ²(3) = 5.65, p = 0.13). CONCLUSION: We discovered a significant positive association between smoking and a positive, but not statistically significant, correlation between age, BMI, and drinking, as well as a microdeletion. There are probably a lot of unidentified variables that affect successful fertilization and implantation. These could include variables that affect fertility and the success of reproduction on an environmental, genetic, and epigenetic level. The study reveals that Y chromosome microdeletion and other epidemiological factors coexist concurrently in cases of infertility. Assessing these variables is crucial for infertile patients. A community-based, comprehensive survey is required to assess the overall consequences of various epidemiological factors on infertility.

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Malfunction in spermatogenesis due to genetic diseases, trauma, congenital disorders or gonadotoxic treatments results in infertility in approximately 7% of males. The behavior of spermatogonial stem cells (SSCs) within three-dimensional, multifactorial, and dynamic microenvironment implicates a niche that serves as a repository for fertility, since can serve as a source of mature and functional male germ cells. Current protocols enable reprogramming of mature somatic cells into induced pluripotent stem cells (iPSCs) and their limited differentiation to SSCs within the range of 0-5%. However, the resulting human iPSC-derived haploid spermatogenic germ cell yield in terms of number and functionality is currently insufficient for transfer to infertility clinic as a therapeutic tool. In this article, we reviewed the evolution of experimental culture platforms and introduced a novel iPSCs-based approach for in vitro spermatogenesis based on a niche perspective bearing cellular, chemical, and physical factors that provide the complex arrangement of testicular seminiferous tubules embedded within a vascularized stroma. We believe that bioengineered organoids supported by smart bio-printed tubules and microfluidic organ-on-a-chip systems offer efficient, precise, personalized platforms for autologous pluripotent stem cell sources to undergo the spermatogenetic cycle, presenting a promising tool for infertile male patients with complete testicular aplasia.

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This research presents a case study involving a 39-year-old male and his 34-year-old female partner seeking fertility consultation in Maharashtra, India, after struggling to conceive for over three years. Despite the male participant's lack of discernible medical conditions and typical lifestyle, semen analysis revealed severe oligozoospermia attributed to elevated stress levels from his physically demanding occupation and infertility-related emotional strain. The female partner exhibited normal blood parameters, including anti-Müllerian hormone (AMH). Embracing holistic approaches, the couple integrated yoga and Yoga Nidra into their daily routine to address stress-induced hormonal imbalances. The customized yoga regimen is aimed at stress reduction and overall well-being, incorporating physical postures, breathing exercises, and meditation. Yoga Nidra, a guided relaxation technique, was employed to induce profound rest and alleviate stress. Over a 12-week period, the male participant diligently adhered to the regimen, reporting heightened relaxation, improved sleep quality, and reduced stress levels. Semen analysis before and after intervention showed significant improvements in sperm count and motility alongside diminished morphological abnormalities. In parallel, the female partner underwent intrauterine insemination (IUI), resulting in a positive beta-human chorionic gonadotropin (ß-hCG) analysis. Weekly follow-ups monitored progress, with supplementation administered as needed. While promising, further research with larger sample sizes and controlled trials is warranted to establish definitive efficacy. Overall, yoga and Yoga Nidra offer noninvasive adjuncts to conventional therapies for male infertility, underscoring the importance of integrating holistic practices into comprehensive fertility management strategies.

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OBJECTIVE: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. METHODS: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). RESULTS: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the control groups. CONCLUSION: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

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Objective: To compare clinical outcomes between nonindicated intracytoplasmic sperm injection (ICSI) and conventional insemination. Design: Autologous cycles performed from 2014-2017 were identified, excluding frozen oocyte cycles. Outcomes were compared between conventional insemination (in vitro fertilization [IVF]) and nonindiated ICSI and analyzed separately for fresh, frozen-thawed preimplantation genetic testing (PGT) and frozen-thawed non-PGT cycles. Setting: US-based fertility clinics reporting to the Society for Assisted Reproductive Technology. Participants: A total of 187,520 patients underwent 318,930 cycles, 57,516 (18.0%) using conventional IVF and 261,414 ICSI (82.0%). Interventions: Intracytoplasmic sperm injection, with or without indications (male factor, prior fertilization failure or any PGT [2012 recommendations]/single-gene PGT [2020 recommendations]). Main Outcome Measures: Odds ratios (ORs) for live birth rates and clinical pregnancy rates were calculated after multivariable adjustment for maternal age, body mass index, infertility etiologies, prior IVF births, and number oocytes retrieved. Results: Intracytoplasmic sperm injection was indicated in 151,627 (58.0%) of cycles according to 2012 American Society for Reproductive Medicine Practice Committee recommendations, and 108,895 (41.7%) according to 2020 recommendations. In multivariable models, nonindicated ICSI among fresh cycles was associated with reduced odds of completing a blastocyst-stage transfer (OR, 0.72; 95% confidence interval [CI] [0.7, 0.75]; P<.001), resulting in reduced odds of live birth (OR, 0.80; 95% CI [0.78, 0.83]; P<.001). Among completed fresh transfers, clinical pregnancy and live birth rates were comparable between nonindicated ICSI and IVF. Nonindicated ICSI in frozen-thawed cycles with PGT and without PGT was associated with comparable live birth and clinical pregnancy rates with IVF in multivariable models. Conclusion: Nonindicated ICSI was associated with reduced blastocyst availability in fresh cycles compared with IVF, leading to lower live birth rates. Outcomes from completed transfers were clinically comparable.

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This retrospective cohort study examines the association between male smoking status and embryo development in vitro. The study included non-smoking women aged under 40 years who underwent in vitro fertilization (IVF) at Yanaihara Women's Clinic from May 2019 to May 2022, and they were divided into two groups according to the husband's smoking status. The effect of male smoking status on IVF outcomes was compared retrospectively based on embryonic development using a time-lapse incubator. A total of 184 patients were included; 272 oocytes of 45 female non-smokers were cultured with the sperm of male smokers, and 816 oocytes of 139 female non-smokers were cultured with the sperm of male non-smokers. No significant differences were observed between male smokers and non-smokers groups with regard to fertilization and the top-quality embryo on day 3 and day 5 (p > 0.05). The male smoker group's embryos reached the early cleavage-stage parameters (time of pronuclei appearance to the five-cell stage) significantly earlier than the male non-smoker group's embryos (p < 0.05). However, no significant differences were observed between the two groups in other parameters of top-quality blastocysts (p > 0.05). It was concluded that male smoking has some differences on the timing of early embryonic events on time-lapse examination.

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The well-documented relationship between chronological age and the sperm methylome has allowed for the construction of epigenetic clocks that estimate the biological age of sperm based on DNA methylation, which we previously termed sperm epigenetic age (SEA). Our lab demonstrated that SEA is positively associated with the time taken to achieve pregnancy; however, its relationship with semen parameters is unknown. A total of 379 men from the Longitudinal Investigation of Fertility and Environment (LIFE) study, a non-clinical cohort, and 192 men seeking fertility treatment from the Sperm Environmental Epigenetics and Development Study (SEEDS) were included in the study. Semen analyses were conducted for both cohorts, and SEA was previously generated using a machine learning algorithm and DNA methylation array data. Association analyses were conducted via multivariable linear regression models adjusting for BMI and smoking status. We found that SEA was not associated with standard semen characteristics in SEEDS and LIFE cohorts. However, SEA was significantly associated with higher sperm head length and perimeter, the presence of pyriform and tapered sperm, and lower sperm elongation factor in the LIFE study (p < 0.05). Based on our results, SEA is mostly associated with defects in sperm head morphological factors that are less commonly evaluated during male infertility assessments. SEA shows promise to be an independent biomarker of sperm quality to assess male fecundity.

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OBJECTIVE: This study evaluated embryological and clinical outcomes in couples with severe male factor infertility versus those with normozoospermia undergoing ICSI and in vitro fertilisation. METHODS: This multicentre, retrospective cohort study included all couples who had undergone autologous ICSI cycles at My Duc Hospital and My Duc Phu Nhuan Hospital in Vietnam between January 2018 and January 2021 (female age < 35 years and males with severe male factor or normozoospermia based on the World Health Organization 2010 criteria). The primary outcome was the cumulative live birth rate after the first ICSI cycle. RESULTS: A total of 1296 couples were included, including 648 with severe male factor infertility and 648 with normozoospermia. The number of two pronuclei zygotes, embryos, and frozen embryos was significantly lower in couples with severe male factor infertility compared with normozoospermia (p < 0.05). In contrast, there were no significant differences between the two groups with respect to cumulative pregnancy outcomes, including the live birth rate, and secondary outcomes including clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate. CONCLUSION: Severe male factor infertility appeared to have an impact on the fertilisation and early developmental potential of embryos, but sperm quality did not affect cumulative clinical fertility outcomes.

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The underlying reasons for male-factor infertility are often unknown. 30% of all men have unexplained semen analysis abnormalities. Moreover, 15%-40% of infertile men have normal semen analyses. There have been increasing efforts to identify causes and associations that may explain idiopathic male-factor infertility. Telomeres have become an area of considerable interest in the field because of the essential roles they have in cellular division and genome integrity. Research to date most consistently supports that men with infertility have shorter sperm telomere length (STL); however, associations between shorter STL and meaningful reproductive health outcomes are less consistent. There is a major need for additional studies to better identify the role of STL in male reproductive health and use the information to improve the counseling and treatment of couples with idiopathic male-factor infertility.

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OBJECTIVE: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. METHODS: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). RESULTS: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. CONCLUSION: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

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OBJECTIVE: To perform a comprehensive assessment of protamine (P) isoforms and modifications in human sperm with the aim of identifying how P modifications and isoforms are altered in men with reduced sperm motility and low sperm count. DESIGN: Cross-sectional. SETTING: Academic medical center. PATIENTS: A total of 18 men with prior reported pregnancy and normozoospermia (normal sperm), 14 men from couples with infertility and asthenozoospermia (reduced sperm motility), and 24 men from couples with infertility and oligoasthenoteratozoospermia (low sperm count and motility and abnormal sperm morphology). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Proteomic assessment using both top-down and bottom-up liquid chromatography mass spectrometry (MS) analysis. RESULTS: A total of 13 posttranslational modifications were identified on P1 and P2 using bottom-up MS, including both phosphorylation and methylation. Top-down MS revealed an unmodified and phosphorylated isoform of P1 and the 3 major isoforms of P2, HP2, HP3, and HP4. Protamine 1 phosphorylation was overall higher in men with male factor infertility compared with those with normal semen analysis (40.5% vs. 32.6). There was no difference in P posttranslational modifications or isoforms of P2 in men with normal vs. abnormal fertility. CONCLUSION: Human protamines bear a number of posttranslational modifications, with alterations in P1 phosphorylation noted in the setting of male factor infertility.