Associations between Sperm Epigenetic Age and Semen Parameters: An Evaluation of Clinical and Non-Clinical Cohorts.

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.

Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice.

Total fertilization failure (TFF) can occur during in vitro fertilization (IVF) treatments, even following intracytoplasmic sperm injection (ICSI). Various male or female factors could contribute to TFF. Increasing evidence suggested that genetic variations in PLCZ1, which encodes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1 (PLCζ), is involved in oocyte activation and is a key male factor in TFF. In the present study, we explored the genetic variants in male individuals that led to TFF. A total of 54 couples with TFF or poor fertilization (fertilization rate < 20%) were screened, and 21 couples were determined to have a male infertility factor by the mouse oocyte activation test. Whole-exome sequencing of these 21 male individuals identified three homozygous pathogenic variants in ACTL9 (actin like 9) in three individuals. ACTL9 variations led to abnormal ultrastructure of the perinuclear theca (PT), and PLCζ was absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF. The key roles of ACTL9 in the PT structure and TFF after ICSI were further confirmed in an Actl9-mutated mouse model. Furthermore, assisted oocyte activation by calcium ionophore exposure successfully overcame TFF and achieved live births in a couple with an ACTL9 variant. These findings identified the role of ACTL9 in the PT structure and the correct localization of PLCζ. The results also provide a genetic marker and a therapeutic option for individuals who have undergone ICSI without successful fertilization.

Efficacy of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.

INTRODUCTION: The use of intracytoplasmic sperm injection (ICSI) has dramatically increased in patients with non-male factor infertility during the last decades. However, whether ICSI provides a significant benefit over in vitro fertilization (IVF) in these patients is still controversial. In this study, we aimed to investigate the efficacy of ICSI on reproductive outcomes with non-male factor infertility and to provide updated evidence for clinical practice. MATERIAL AND METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2023. Randomized controlled trials (RCTs) comparing the efficacy between ICSI and IVF in patients with non-male factor infertility were included. The main outcomes were the live birth rate (LBR), fertilization rate (FR), and total fertilization failure (TFF). The pooled estimates were calculated using the random-effects models as relative risk (RR) with 95% confidence intervals (CIs). This systematic review and meta-analysis was registered in PROSPERO (CRD42023427004). RESULTS: We included 18 RCTs with 3249 cycles and 30 994 oocytes. The results demonstrated that ICSI reduced the risk of TFF (RR = 0.26, 95% CI: 0.13-0.50, I2 = 58%) and increased FR per oocyte inseminated/injected (RR = 1.14, 95% CI: 1.08-1.20, I2 = 69%), but it did not improve LBR (RR = 1.11, 95% CI: 0.94-1.30, I2 = 0%) or other outcomes compared with IVF. However, the difference in fertilization failure reduction between ICSI and IVF may be explained by different randomization methods (randomization based on patients vs. sibling oocytes). When considering only studies with randomization based on patients, we found no evidence of the difference between the groups (RR = 0.72, 95% CI: 0.48-1.06, I2 = 0%). Furthermore, no differences were observed in subgroup analyses based on other factors, including female age, study period, and controlled ovarian stimulation protocols. CONCLUSIONS: Our findings suggest that ICSI leads to no difference in reproductive outcomes compared to IVF in patients with non-male factor infertility. Considering the cost and safety of ICSI, we have no evidence to support the routine use of ICSI in these populations. High-quality RCTs with large sample sizes will be needed to confirm our results and explore clinical and neonatal outcomes.

The prevalence of abnormal semen parameters in male partners of women with anovulatory polycystic ovarian syndrome: a retrospective case-control study.

PURPOSE: Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility, often requiring ovarian stimulation in affected women attempting to conceive. Male partner semen quality and shared lifestyle factors can significantly impact reproductive outcomes. However, current international guidelines lack evidence-based recommendations on the necessity and timing of semen analysis for the fertility management of anovulatory PCOS women. METHODS: In a retrospective case-control study, semen analysis results of male partners of 187 anovulatory PCOS women scheduled for ovarian stimulation were analyzed and compared to a control group of 76 male partners of women with bilateral tubal occlusion. RESULTS: The prevalence of semen analysis results with at least one parameter classified as "borderline" and "pathological" among male partners of women with PCOS eligible to undergo ovarian stimulation was 51.3% and 22.5%, compared to 44.7% and 13.2% in the control group, respectively (p = 0.027). In the PCOS group, male body mass index (odds ratio, OR 1.478, p < 0.001), and smoking status (OR 6.228, p < 0.001) were significant predictors of pathological sperm test results, while no association was observed with any female characteristics (p > 0.05). CONCLUSION: The high frequency of pathological sperm analysis results provides lacking epidemiological data on semen quality in this population, emphasizing the critical need for early male fertility evaluation prior to ovarian stimulation in PCOS women. Moreover, our findings indicate that the risk prediction for abnormal semen quality cannot be based on the female's data.

Comparative motility assessment of sperm retrieved from micro-testicular sperm extraction: A single-centre study comparing fresh and frozen-thawed sperm.

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.

High sperm DNA fragmentation increased embryo aneuploidy rate in patients undergoing preimplantation genetic testing.

RESEARCH QUESTION: Is high sperm DNA fragmentation (SDF) associated with a high embryonic aneuploidy rate in patients undergoing intracytoplasmic sperm injection (ICSI)-preimplantation genetic testing (PGT)? DESIGN: This was a retrospective study of 426 couples with normal karyotypes undergoing ICSI-PGT at the authors' centre from March 2017 to March 2021. SDF was assessed using the sperm chromatin structure assay. The population was divided into low and high SDF groups according to cut-off values found by the receiver operating characteristic (ROC) curve. A 1:1 ratio propensity score matching (PSM) method was used to control for potential confounding factors, and a generalized linear mixed model was established to evaluate the relationship between SDF and the embryonic aneuploidy rate. RESULTS: The ROC curve indicated a threshold of 30%. In total, 132 couples were included after PSM, and the high SDF group (>30%) had significantly higher SDF (40.74% ± 9.78% versus 15.54% ± 7.86%, P < 0.001) and a higher embryo aneuploidy rate (69.36% versus 53.96%, P < 0.001) compared with the low SDF group (≤30%). The two pronuclear fertilization rate, cleavage rate, rate of high-quality embryos at day 3 rate, blastocyst rate, biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, caesarean section rate, preterm birth rate, singleton rate and low birthweight rate were similar in both groups (P > 0.05). After PSM, SDF > 30% was significantly correlated with an increased embryo aneuploidy rate after adjusting for all confounding variables (adjusted odds ratio 1.70, 95% CI 1.00-2.88, P = 0.049). CONCLUSIONS: SDF > 30% was associated with an increased embryo aneuploidy rate in couples with normal karyotypes undergoing PGT, but did not affect embryonic and clinical outcomes after transfer of euploid embryos.

Male factor infertility and assisted reproductive technologies: indications, minimum access criteria and outcomes.

BACKGROUND: Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15-20% of couples worldwide and a male factor is involved in about half of the cases. The development of assisted reproductive technology (ART) made it possible to conceive also to individuals affected from severe oligospermia or azoospermia. However, the impact of the male factor on embryo development, implantation, prevalence of chromosomal abnormalities, genetic and epigenetic alterations, and clinical and obstetric outcomes is still controversial. PURPOSE: This narrative review examines the indications, minimum access criteria, and outcomes by individual ART technique in relation to the male factor.

Intracytoplasmic sperm injection cycle success in patients under 35 years old with diminished ovarian reserve plus severe male factor.

OBJECTIVE: We aimed to evaluate intracytoplasmic sperm injection (ICSI) outcomes in young patients with diminished ovarian reserve (DOR) plus severe male factor (SMF) compared with age-matched controls with DOR. STUDY DESIGN: A total of 189 infertile women under 35 years with DOR undergoing ICSI procedures were included retrospectively. Participants whose partners' sperm analysis was normal considered as the DOR group (n = 154) and whose partners' had SMF considered as the DOR + SMF group (n = 35). The two groups were compared regarding cycle characteristics and pregnancy outcomes. RESULTS: Demographic features except infertility duration were similar between two groups. The duration of infertility was significantly longer in the DOR + SMF group compared to the DOR group (p = 0.02). Ovarian stimulation characteristics, oocyte retrieval parameters, fertilization rate, quality of embryos, embryo cancellation rate, and development up to blastocyst stage were found similar between two groups. Implantation, clinical pregnancy, abortion, and live birth rate, multiple pregnancy rate per cycle were distributed homogenously between the DOR and DOR + SMF groups. Regarding perinatal and neonatal outcomes of groups, fetal height and weight were significantly lower in DOR + SMF group than in DOR group (p = 0.001 and 0.01, respectively). Gestational week at delivery was lower in the DOR + SMF group compared to the DOR group (p < 0.0001). CONCLUSION: Fetal anthropometric measures were lower regarding to preterm delivery in the DOR + SMF group than the DOR group. Large sample-sized studies should be performed to explain the decreased gestational week at the time of delivery in the DOR + SMF group.

Comparison of clinical and preimplantation genetic testing for aneuploidy outcomes between in vitro fertilization and intracytoplasmic sperm injection in sibling mature oocytes from high-risk patients: A retrospective study.

AIM: To evaluate the influence of insemination methods on clinical outcomes by assessing preimplantation genetic testing for aneuploidy (PGT-A) outcomes in embryos obtained using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling mature oocytes from high-risk patients. METHODS: This retrospective study involved 108 couples with nonmale or mild male factor infertility who underwent split insemination cycles from January 2018 to December 2021. PGT-A was performed using trophectoderm biopsy, array comparative genome hybridization, or next-generation sequencing with 24-chromosome screening. RESULTS: Mature oocytes were divided into IVF (n = 660) and ICSI (n = 1028) groups. The normal fertilization incidence was similar between the groups (81.1% vs. 84.6%). The total number of blastocysts biopsied was significantly higher in the IVF group than in the ICSI group (59.3% vs. 52.6%; p = 0.018). However, euploidy (34.4% vs. 31.9%) and aneuploidy (63.4% vs. 66.2%) rates per biopsy and clinical pregnancy rates (60.0% vs. 58.8%) were similar between the groups. Implantation (45.6% vs. 50.8%) and live birth or ongoing pregnancy (52.0% vs 58.8%) rates were slightly higher in the ICSI group than in the IVF group and miscarriage rate per transfer was slightly higher in the IVF group than in the ICSI group (12.0% vs 5.9%); however no significant difference was observed. CONCLUSIONS: IVF and ICSI using sibling mature oocytes had similar clinical outcomes, and euploidy and aneuploidy rates in couples with nonmale and mild male factor infertility. These results suggest that IVF is a useful option, along with ICSI, as an insemination method in PGT-A cycles, especially in high-risk patients.

IVF outcomes following ICSI cycles using testicular sperm in obstructive (OA) vs. non-obstructive azoospermia (NOA) and the impact of maternal and paternal age: a SART CORS data registry.

PURPOSE: To assess the differences in IVF outcomes between couples with obstructive azoospermia (OA), non-obstructive azoospermia (NOA), and male factor (MF). METHODS: Using the SART CORS data from 2016 to 2017, we included all initial autologous cycles with a diagnosis of male factor with ejaculated and surgically obtained sperm. We analyzed 71,121 cycles, including 3467 with a diagnosis of azoospermia and 67,654 with other non-azoospermic MF. Using a multivariate binomial regression, we estimated adjusted risk ratios comparing outcomes for ICSI cycles using surgically acquired (OA and NOA) versus ejaculated sperm (MF). Outcomes reported per initial cycle included clinical pregnancy, live birth, biochemical pregnancy, and miscarriage. Outcomes reported per singleton pregnancy included full-term delivery (≥ 37 weeks), normal birth weight (≥ 2500 g), and delivery method. RESULTS: After frozen embryo transfers (FET), patients with NOA had 7% higher odds of live birth compared to MF (aOR 1.23 (0.94-1.74)), and those with OA had 2.6% lower chance of live birth compared to MF (aOR 0.73 (95%CI 0.5-1.05)). After fresh ET, patients with NOA had 5% higher chance of live birth (aOR 1.11 (0.9-1.36)), and those with OA had a 2.5% higher chance of live birth (aOR 1.10 (95%CI 0.89-1.34)) compared to MF. All three subgroups had lower fresh live birth rates (LBR) compared to FETs. CONCLUSION: Couples with either NOA or OA have overall comparable ART and perinatal outcomes to couples with MF, and their success is primarily dependent on both patient's and partner's age.

Computer software (SiD) assisted real-time single sperm selection associated with fertilization and blastocyst formation.

RESEARCH QUESTION: Is it possible to explore an association between individual sperm kinematics evaluated in real time and spermatozoa selected by an embryologist for intracytoplasmic sperm injection (ICSI), with subsequent normal fertilization and blastocyst formation using a novel artificial vision-based software (SiD V1.0; IVF 2.0, UK)? DESIGN: ICSI procedures were randomly video recorded and subjected to analysis using SiD V1.0, proprietary software developed by our group. In total, 383 individual spermatozoa were retrospectively analysed from a dataset of 78 ICSI-assisted reproductive technology cycles. SiD software computes the progressive motility parameters, straight-line velocity (VSL) and linearity of the curvilinear path (LIN), of each sperm trajectory, along with a quantitative value, head movement pattern (HMP), which is an indicator of the characteristics of the sperm head movement patterns. The mean VSL, LIN and HMP measurements for each set of spermatozoa were compared based on different outcome measures. RESULTS: Statistically significant differences were found in VSL, LIN and HMP among those spermatozoa selected for injection (P < 0.001). Additionally, LIN and HMP were found to be significantly different between successful and unsuccessful fertilization (P = 0.038 and P = 0.029, respectively). Additionally, significantly higher SiD scores were found for those spermatozoa that achieved both successful fertilization (P = 0.004) and blastocyst formation (P = 0.013). CONCLUSION: The possibility of carrying out real-time analyses of individual spermatozoa using an automatic tool such as SiD creates the opportunity to assist the embryologist in selecting the better spermatozoon for injection in an ICSI procedure.

The impact of male factors and their correct and early diagnosis in the infertile couple's pathway: 2021 perspectives.

PURPOSE: The current clinical practice in reproductive medicine should pose the couple at the centre of the diagnostic-therapeutic management of infertility and requires intense collaboration between the andrologist, the gynaecologist and the embryologist. The andrologist, in particular, to adequately support the infertile couple, must undertake important biological, psychological, economical and ethical task. Thus, this paper aims to provide a comprehensive overview of the multifaceted role of the andrologist in the study of male factor infertility. METHODS: A comprehensive Medline, Embase and Cochrane search was performed including publications between 1969 and 2021. RESULTS: Available evidence indicates that a careful medical history and physical examination, followed by semen analysis, always represent the basic starting points of the diagnostic work up in male partner of an infertile couple. Regarding treatment, gonadotropins are an effective treatment in case of hypogonadotropic hypogonadism and FSH may be used in men with idiopathic infertility, while evidence supporting other hormonal and nonhormonal treatments is either limited or conflicting. In the future, pharmacogenomics of FSHR and FSHB as well as innovative compounds may be considered to develop new therapeutic strategies in the management of infertility. CONCLUSION: To provide a high-level of care, the andrologist must face several critical diagnostical and therapeutical steps. Even though ART may be the final and decisive stage of this decisional network, neglecting to treat the male partner may ultimately increase the risks of negative outcome, as well as costs and psychological burden for the couple itself.

Duration of infertility and assisted reproductive outcomes in non-male factor infertility: can use of ICSI turn the tide?

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is increasingly used among in vitro fertilization (IVF) cycles without male factor infertility. For couples with prolonged infertility duration, the preferred insemination method may vary across laboratories and clinics. We analyzed whether ICSI is effective for non-male factor infertility with long infertility duration. METHODS: Seventeen thousand four hundred seventy-seven IVF/ICSI cycles from women with non-male factor infertility were included, of these 4177 women with infertility duration ≥ 5 years were in the final analysis. Primary outcome was the live birth rate after first embryo transfer. Secondary outcomes were rates of clinical pregnancy and fertilization. RESULTS: A nonlinear relationship was observed between infertility duration and IVF fertilization rate, which decreased with infertility years up to the turning point (4.8 years). 4177 women with infertility ≥ 5 years were categorized by IVF (n = 3806) or ICSI (n = 371). Live birth rate after first embryo transfer was 43.02% in ICSI and 47.85% in IVF group (adjusted odds ratio (aOR), 0.91; 95% confidence interval (CI), 0.72-1.15). Fertilization rate per metaphaseII (aOR, 1.10; 95% CI, 0.86-1.40) and clinical pregnancy rate (aOR, 0.89; 95% CI, 0.71-1.13) were similar between the two groups. Sensitive analyses (women ≥ 35 years) did not show a benefit of ICSI over IVF. CONCLUSIONS: Women with infertility exceeding 4.8 years had decreased incidence of IVF fertilization. The use of ICSI showed no significant improvement in fertilization and live birth rates for non-male factor couples with ≥ 5 years of infertility.

Sperm DNA integrity does play a crucial role for embryo development after ICSI, notably when good-quality oocytes from young donors are used.

Based on the inconsistent literature published thus far involving infertile patients, whether intracytoplasmic sperm injection (ICSI) allows overcoming total fertilization failure due to sperm DNA fragmentation is still unclear. Related to this, female factors, which may have a significant impact on assisted reproduction outcomes, can mask male infertility. In this scenario, evaluating ICSI outcomes following cycles using healthy donor gametes could shed light on this realm, as it would avoid the influence of (un)known confounding factors present in infertile individuals. The present work, therefore, aimed to address whether single- and double-stranded sperm DNA fragmentation leads to impaired ICSI outcomes in double gamete donation cycles. The study also compared these double-gamete donation cycles to cycles in which only sperm were donated and oocytes were obtained from infertile patients. Two cohorts were included: (a) the Donor-Donor (DD) cohort, which included 27 semen donor samples used in 49 ICSI cycles with young healthy oocyte donors; and (b) the Donor-Infertile (DI) cohort, which involved 34 semen donor samples used in 57 ICSI cycles with oocytes from patients. Single- and double-stranded sperm DNA breaks were determined with alkaline and neutral Comet assays, respectively; ICSI was conducted following standard protocols and embryos were monitored through time-lapse microscopy. In the DD cohort, the percentage of sperm with high overall DNA damage correlated with fertilization rates (Rs = - 0.666; P < 0.001) and with the percentage of blastocysts per injected oocyte (Rs = - 0.414; P = 0.040). In addition, sperm DNA damage delayed the first embryo division (Rs = 0.421; P = 0.036), and development from the 8-cell to the morula stage (Rs = 0.424; P = 0.034). In contrast, double-stranded DNA breaks had no effect in this cohort. As far as the DI cohort is concerned, while overall sperm DNA damage was not found to be correlated to fertilization or blastocyst rates, pronuclei formation following ICSI was delayed when the incidence of double-stranded DNA breaks was high (Rs = 0.485; P = 0.005). In conclusion, this study, which is the first involving double donation cycles (i.e., a donor-donor cohort), supports that sperm DNA damage has a detrimental impact on fertilization rates after ICSI, and delays embryo development. Moreover, the use of oocytes from infertile individuals is suggested to hide the male-factor effect.

Can sperm quality influence embryo development and its ploidy? Analysis of 811 blastocysts obtained from different sperm sources.

The aim of our study was to evaluate the correlation between sperm quality and ploidy status of the derived blastocysts. We performed a retrospective analysis on a restricted pool of patients enrolling only those who had no female factors. Male patients with genetic factors affecting spermatogenesis were also excluded. We chose a maternal age ≤38 years to decrease the female factor, therefore the male factor was the main component of sterility. We divided the patients in four groups based on semen quality and comparing fertilization, pregnancy and euploidy rates above all. In total, 201 intracytoplasmic sperm injection (ICSI) cycles were enrolled in the study. Cycles were divided into four groups, according to semen source: normal semen, oligoasthenoteratozoospermia (OAT), cryptospermia or non-obstructive azoospermia (NOA). An extremely statistically lower fertilization rate was found in NOA patients. Unexpectedly, no differences were detected in blastocyst formation, euploidy, aneuploidy and mosaicism rates among the four groups. Interestingly, we also found a higher abortion rate comparing NOA to normal semen with an odds ratio of 4.67. In our study no statistically significant differences among the analyzed groups were found, showing little or no effect at all using spermatozoa from different semen sources or quality. This may be linked to the oocyte competence of fixing sperm DNA damage and it could be hypothesized that only sperm with a good rate of DNA integrity are able to fertilize the oocyte, explaining why poor quality semen is reflected in a low fertilization rate without effect on ploidy.

Switching to testicular sperm after a previous ICSI failure with ejaculated sperm significantly improves blastocyst quality without increasing aneuploidy risk.

PURPOSE: The use of testicular sperm is confined to patients with azoospermia, but there is evidence to support its use in males with poor semen parameters and/or previous intracytoplasmic sperm injection (ICSI) failures with ejaculated spermatozoa. We compared the aneuploidy rate and quality between embryos derived from ICSI cycles with ejaculated sperm (EJ-ICSI) and those from ICSI cycles using testicular spermatozoa (TT-ICSI) within the same couple. METHODS: Retrospective study of 27 couples who first underwent an EJ-ICSI cycle that did not result in a livebirth and afterwards a TT-ICSI cycle. Only the two closer cycles of each couple were included. Preimplantation genetic test for aneuploidies (PGT-A) was performed in both ICSI cycles and classic parameters of embryo quality were assessed until blastocyst-stage. RESULTS: A total of 375 embryos from 54 ICSI cycles were evaluated. Aneuploidy rate was measured by two different parameters. Patients undergoing TT-ICSI presented a similar aneuploidy rate as EJ-ICSI group: 30.7% (23.4-38.0) vs 26.8% (18.1-35.5) per inseminated oocytes (P>0.05), and 76.2% (66.2-86.2) vs 72.1% (59.1-85.2) per the total number of biopsied embryos (P>0.05), respectively. Further, the good-quality blastocyst rate per correctly fertilized oocyte was significantly higher in TT-ICSI group (33.6% (30.4-36.9)) than EJ-ICSI group (24.2% (20.3-28.0)) (P<0.001). CONCLUSIONS: Switching to testicular sperm for ICSI yielded better-quality blastocysts without affecting the chromosomal load of the embryos in non-azoospermic couples with a previous unsuccessful ICSI using ejaculated sperm. This strategy is a good option for couples seeking a livebirth who do not want to use donor sperm.

The effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life and sexual function parameters: a prospective, cross-sectional study from Turkey.

OBJECTIVES: Despite the development of diagnosis and treatment methods, the psychological effects of infertility on women were not adequately addressed. This study investigated the effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life, and sexual function parameters. METHODS: In this prospective, cross-sectional study, 480 women [n = 234, with male factor infertility (MFI) (MFI group) and n = 246, with female factor infertility (FFI) (FFI group)], who could not conceive despite unprotected intercourse for 1 year, and 242 fertile healthy women (control group) who had children within the last 1 year were included. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Rosenberg Self Esteem Scale (RSES), Fertility Quality of Life (FertiQol) and Female Sexual Function Index (FSFI) questionnaires were used for patients' evaluation. RESULTS: RSES, BAI and BDI-II scores were significantly higher and FSFI score was significantly lower in the FFI group compared to other groups. RSES, BAI and BDI-II scores were also significantly higher and FSFI score was significantly lower in the MFI group compared to the control group. FertiQol total score was significantly lower in the FFI group compared to the MFI group. RSES score was positively correlated with BDI-II and BAI scores; however, it was negatively correlated with FertiQol and FSFI scores. CONCLUSIONS: The negative psychological effects of infertility are ignored by many centres, especially in the treatment process of infertility. Regardless of the infertility factor (male or female), we believe that psychological support should be given to all women to improve their life quality.

Correlation between Sperm Micro Ribonucleic Acid-34b and -34c Levels and Clinical Outcomes of Intracytoplasmic Sperm Injection in Men with Male Factor Infertility.

Few studies have examined the correlation between sperm miRNA levels and clinical outcomes of intracytoplasmic sperm injection (ICSI). In this study, we aimed to assess the correlation of sperm miR-34b, miR-34c, miR-122, and miR-429 levels with ICSI outcomes in men with teratozoospermia and asthenozoospermia. TaqMan microRNA quantitative polymerase chain reaction was used to evaluate the relative expression of miRNAs in sperm. The relative miRNA levels quantified using a comparative method found that the four miRNAs were not associated with fertilization rate and early embryo development. However, revels of miR-34b and miR-34c in teratozoospermia sperm of the live birth group were significantly higher than those in the non-live birth group. Receiver operating characteristic curve analysis revealed that the optimal cut-off delta cycle threshold values of miR-34b and miR-34c were 8.630 and 7.883, respectively. Statistical analysis found that the levels of miR-34b and the miR-34c in teratozoospermic and asthenozoospermic sperm above the thresholds were not associated with the fertilization rate and the high-quality embryo rate above 50%; however, they were more likely to exhibit higher implantation, pregnancy, and live birth rates. miR-34b and miR-34c were significantly associated with ICSI clinical outcomes in male factor infertility, especially teratozoospermia. Further validation is required before it becomes a clinically valid reference indicator.

Does endometrial thickness affect pregnancy outcomes in isolated male infertility IVF cycles? A retrospective cohort study.

In our retrospective cohort study, we aimed to determine the role of endometrial thickness (ET) in isolated male factor infertile women in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo cycles. The patients were classified as having an endometrial thickness of <7 mm (n: 80), 7-9.9 mm (n: 335), 10-14 mm (n: 579) and >14 mm (n: 50) according to their ETs on the human chorionic gonadotropin (hCG) day. The overall clinical pregnancy rate was 37.4%, and no significant difference was found between the groups (p = .262). There was no significant difference between live birth rates (p = .094), but the highest pregnancy (46%) and live birth (34%) rates were found in the group with >14 mm ET. The increase in ET in IVF cycles increases pregnancy rates, albeit partially. When it is desired to determine a cut-off value, it can be said that pregnancy rates increase significantly in thicknesses of 14 mm and above.Impact StatementWhat is already known on this subject? When the literature is examined, many studies conclude that clinical pregnancy rates increase with the increase in endometrial thickness (ET) in IVF cycles, but there are also studies that argue the opposite. There is no study in the literature investigating the effect of ET on clinical pregnancy rates in patients with isolated male factor infertility.What do the results of this study add? In support of the literature, an increase in ET was found to be associated with an increase in clinical pregnancy rates, regardless of male and female factors. Although pregnancy occurs in thin endometriums, abortion rates are undesirably high.What are the implications of these findings for clinical practice and/or further research? Although the risk of abortion is high in thin endometriums, live birth rates are satisfactory. As a result, thin endometrium does not require cycle cancellation.

Female causes of infertility are associated with higher risk of preterm birth and low birth weight: analysis of 117 401 singleton live births following IVF.

STUDY QUESTION: Does the cause of infertility affect the perinatal outcomes preterm birth (PTB) and low birth weight (LBW) following IVF treatment? SUMMARY ANSWER: The risk of PTB and LBW was higher with female causes of infertility-ovulatory disorders, tubal disorders and endometriosis-compared to unexplained infertility but the absolute increase in risk was low. WHAT IS KNOWN ALREADY: Infertility is associated with an increased risk of adverse perinatal outcomes. Risk of adverse perinatal outcomes is also higher following ART compared to spontaneous conceptions. Infertility can result from female and/or male factors or is unexplained when the cause cannot be delineated by standard investigations. Given that infertility and ART are contributory to the adverse perinatal outcomes, it is a matter of interest to delineate if the specific cause of infertility influences perinatal outcomes following IVF treatment. STUDY DESIGN, SIZE, DURATION: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA). The HFEA has collected data prospectively on all ART cycles performed in the UK since 1991. Data from 1991 to 2016 comprising a total of 117 401 singleton live births following IVF with or without ICSI (IVF ± ICSI) for sole causes of infertility were analysed for PTB and LBW. Cycles having more than one cause of infertility and/or multiple births were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on all women undergoing stimulated IVF ± ICSI treatment cycles were analysed to compare perinatal outcomes of PTB and LBW among singleton live births based on the cause of infertility (ovulatory disorders, tubal disorders, endometriosis, male factor, unexplained). Logistic regression analysis was performed, adjusting for female age category, period of treatment, previous live births, IVF or ICSI, number of embryos transferred and fresh or frozen embryo transfer cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to unexplained infertility, the risk of PTB was significantly higher with ovulatory disorders (adjusted odds ratio (aOR) 1.31, 99.5% CI 1.17 to 1.46); tubal disorders (aOR 1.25, 99.5% CI 1.14 to 1.38) and endometriosis (aOR 1.17, 99.5% CI 1.01 to 1.35). There was no significant difference in the risk of PTB with male factor causes compared to unexplained infertility (aOR 1.01, 99.5% CI 0.93, 1.10). The risk of LBW was significantly higher with ovulatory disorders (aOR 1. 29, 99.5% CI 1.16 to 1.44) and tubal disorders (aOR 1.12, 99.5% CI 1.02 to 1.23) and there was no increase in the risk of LBW with endometriosis (aOR 1.11, 99.5% CI 0.96 to 1.30) and male factor causes (aOR 0.94, 99.5% CI 0.87, 1.03), compared to unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: Although the analysis was adjusted for several important confounders, there was no information on the medical history of women during pregnancy to allow adjustment. The limitations with observational data would apply to this study, including residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to address the causes of infertility affecting perinatal outcomes of PTB and LBW. The information is important for the management of pregnancies and the underlying reasons for the associations observed need to be further understood. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.