Infertile Men Research Articles

Expression of Protamine-1 Gene and Association with Interleukin-12 gene in Infertile Men: A Case-Control Study in Iraqi Patients

Approximately 15% of all couples all over the world suffer from difficulty conceiving their first child. The word "infertility" is used to describe this problem. When a couple had regular, unprotected sexual intercourse for a year or longer, it indicates that they have been unsuccessful in their efforts to conceive. The current investigation aims to find out if there is a relationship between PROTAMIN-1(PRM-1) and INTERLEUKINE-12 (IL-12) gene expressions and their effect on the development of infertility. The current investigation comprised 100 teratozoospermia patients and 100 healthy fertile controls who had their semen examined. Samples were given by Al-Nahrain University's Biotechnology Research Center and the Kamal Al-Samarie IVF Hospital in Baghdad, Iraq. Determinations Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was employed to test the expression of the PRM gene in semen and blood samples, as well as the IL-12 gene in blood samples. And the titer of IL-12 was evaluated in the seminal plasma employing the Enzyme Linked Immune Sorband Assay (ELISA) technique. The difference between the mean threshold cycle (ΔCt) of PRM-1 and IL-12 mRNA in the infertile patient group versus the healthy control group was also statistically significant. Evaluating the means of 2 ̄ΔΔCt revealed an important finding, a decrease in the expression of PRM-1 mRNA in the infertile group in comparison to the control group in the two types of samples. Conversely, there was an increase in the expression of IL-12 mRNA between the two study groups. In infertile Iraqi men, the expression of the PRM-1 gene was found to be down-regulated, whereas the expression of the IL-12 gene was found to be up-regulated. Our data revealed the diagnostic value of these genes and might be considered as predictive biomarkers in infertile people with idiopathic infertility.

Testosterone and luteinizing hormone predict semen parameter improvement in infertile men treated with anastrozole

To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. Multi-institutional retrospective cohort study. Two Tertiary Academic Medical Centers. A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. Prescription of anastrozole (median 3 mg/wk). Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.

The Sperm DNA Fragmentation Assay with SDF Level Less Than 15% Provides a Useful Prediction for Clinical Pregnancy and Live Birth for Women Aged under 40 Years.

This retrospective cohort study was conducted on 1148 males who presented along with their partners for infertility management at the PIVET Medical Centre between 2013 and 2022 and had a sperm DNA fragmentation (SDF) assay performed by Halosperm, thereafter participating in 1600 assisted reproductive technology (ART) cycles utilising one of three modalities, namely, IVF-Only, ICSI-Only or IVF-ICSI Split cycles. The outcomes from the ART cycles were then analysed as two groups based on SDF levels <15% and ≥15%. The study showed the unadjusted fertilization rates were not different between the groups, neither across the four female age ranges. However, when the fertilization rates were adjusted for the mature oocytes (metaphase-II oocytes), there was a highly significant difference in fertilization rates in favour of the group with SDF levels < 15% where the women were in the younger age grouping of <35 years (78.4% vs. 73.0%; p < 0.0001). Overall, there was no difference in the rates of blastocyst development nor clinical pregnancy rates between the two SDF groups, but there was a significantly higher pregnancy rate for the younger women (<35 years) with the group of SDF level < 15% (44.1% vs. 37.4%; p = 0.04). Similarly, there was no difference in the miscarriage rates overall with respect to SDF groups, and no clear picture could be deciphered among the women's age groups. With respect to cumulative live births, this reflected the pregnancy rates with no overall difference between the two SDF groups, but there was a significantly higher cumulative live birth rate for women <35 years where the SDF level was <15% (38.6% vs. 28.6%; p < 0.01). Among the three modalities, the highest cumulative live birth rate occurred within the group with SDF level < 15%, being highest with the IVF mode, particularly for women aged <40 years (43.0% vs. 37.7% for IVF-ICSI Split and 27.9% for ICSI; p = 0.0002), noting that the IVF case numbers were disproportionately low.

Loss-of-function variants in KCTD19 cause non-obstructive azoospermia in humans

Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201_202insAC, p.Tyr68Thrfs∗17) and two nonsense variants (c.1897C>T, p.Gln633∗; c.2005C>T, p.Gln669∗) in KCTD19 (potassium channel tetramerization domain containing 19) from two unrelated infertile Chinese men and a consanguineous Pakistani family with three infertile brothers. Testicular histological analyses revealed meiotic metaphase I (MMI) arrest in the affected individuals. Mice modeling KCTD19 variants recapitulated the same MMI arrest phenotype due to severe disrupted individualization of MMI chromosomes. Further analysis showed a complete loss of KCTD19 protein in both Kctd19 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified KCTD19 variants and highlight an essential role of KCTD19 in MMI chromosome individualization.

Low levels of peroxiredoxins are associated with high iron content and lipid peroxidation in seminal plasma from asthenozoospermic infertile men

Asthenospermia is a common cause of male infertility refers to semen samples with spermatozoa that move slowly or immotile. Recent research has implicated oxidative stress-induced ferroptosis in asthenospermia's pathophysiology. Peroxiredoxins are important players in the antioxidant defense to protect cells against oxidative stress. However, some aspects of the antioxidant response necessary for male fertility are not well understood. This case-control study aimed to elucidate the role of peroxiredoxins in regulating oxidative stress in male fertility via their correlation with ferroptosis. It included 90 fertile and 90 asthenospermic subfertile males from Hilla City, Iraq. Total peroxiredoxin activity, peroxiredoxin-6 level, and peroxiredoxin-4 level were measured alongside the ferroptosis biomarkers glutathione peroxidase-4, malondialdehyde, and the reduced/oxidized protein thiol ratio. Infertile males had significantly higher oxidized thiol and malondialdehyde levels than fertile males (p < 0.05). Total peroxiredoxin activities, peroxiredoxin-6 levels, peroxiredoxin-4 levels, glutathione peroxidase-4 levels, and reduced/oxidized protein thiol ratios were significantly lower in infertile males than in fertile males (p < 0.05). Therefore, peroxiredoxin activity and level correlate with reduced/oxidized protein thiol ratio. They are inversely associated with ferroptosis and directly associated with semen quality. These findings suggest that peroxiredoxins are crucial in preventing ferroptosis and have potential implications for treating asthenospermia.

The Impact of Sexually Transmitted Infections on Male and Female Infertility: Literature Review

Sexually Transmitted Infections (STI) are a global issue with 374 million new infections globally and a prevalence of 6% in 2022 in Indonesia. Sexually transmitted infections have potential causes of infertility. The purpose of this study is to describe the impact of STIs on infertility for both men and women. The research design is a literature review by looking systematically at journals and articles on Google Scholar, Garuda Portal, and Science Direct. The inclusion criteria in this study were journal publications spanning 2018-2022, the outcome studied was to find out that sexually transmitted infections have an impact on the incidence of infertility in men and women. Reviews of 5 selected articles describing the correlation between sexually transmitted infections and infertility, including reviews of men with Chlamydia trachomatis or men and women positive for Human papillomavirus or women with vaginal lactobacilli have the potential for infertility. Microbiological association with experiments using IVF (In Vitro Fertilisation) or pregnancy attempts using IVF shows that 85.7% of microbiologically positive couples have a success rate of 7.5%. Therefore, it can be concluded that sexually transmitted infections have an impact on the incidence of infertility, especially in men compared to women, which are mostly caused by bacteria and viruses that cause sexually transmitted infections. In addition to sexually transmitted infections, it is also caused by poor lifestyle factors such as using drugs, alcoholic beverages and smoking. Efforts are needed to detect symptoms of infertility early, especially in STI sufferers with HIV and AIDS cases.

Management of Female Sterility Due to Tubal Obstruction during Laparoscopic Surgery at the Nianankoro Fomba Hospital in Segou

This is a prospective cross-sectional study which took place at Segou Hospital from 15 January 2019 to 15 January 2022 on the management of female infertility by tubal obstruction in laparoscopic surgery at Segou Hospital on 14 cases. 42.9% were between 31 and 35 years of age. The mean age was 20.3 years, with extremes ranging from 20 to 41 years. Civil servants were the most represented, with 42.9% in our series, followed by shopkeepers with 21.4%. All our patients were married. 78.6% had primary infertility, 21.4% had secondary infertility. The average duration of infertility was 1.9 years, with extremes of 2 and 10 years. Obstetrical outcome after catheterisation was favourable in four (4) of our patients, i.e. 28.6% had a pregnancy after recanalisation compared with 71.4% without pregnancy. Conclusion: The advent of laparoscopic surgery in our country has made it possible to improve care for women suffering from female infertility.

The Impact of Origanum vulgare Supplementation on Human Asthenozoospermic Sperm Parameter Quality.

Male infertility is a complex multifactorial disease and a real health problem; 50% of infertile men have identifiable causes detectable by fundamental sperm analysis. Numerous research studies have shown the possibility of treating abnormal semen samples with some drugs before artificial insemination, yet evidence of the drug's effectiveness remains minimal. In our previous work, we tested the effectiveness of some essential oils, such as eucalyptus (Eucalyptus globulus Labill.), oregano (Origanum vulgare L.), and sage (Salvia officinalis L.) on sperm parameters. The essential oil of oregano showed the best ameliorative effect. In present, we examined the effect of the essential oil of O. vulgare on the physiological parameters and the specific activity of certain antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), lipid peroxidation rate (MDA), and GAPDH and antioxidant and metabolic biomarkers, characterizing the quality of human sperm. The results showed that in vitro supplementation of oregano significantly improves the mobility and antioxidant activities, without harmful effects on the integrity of the sperm's DNA, and that the selected concentration of oregano EO is nontoxic and may be considered a therapeutic alternative to heal sperm motility problems in asthenozoospermic patients.

Высокопроизводительное секвенирование микробиома яичка у пациентов с необструктивной формой азооспермии и сопутствующим варикоцеле.

Introduction. The male factor in infertile marriages accounts for about 50% of all cases, which is associated with changes in the characteristics of the ejaculate microbiota and directly correlates with changes in sperm parameters, including sperm count, motility, and morphology. Purpose of the work: to determine the presence of a correlation between the taxonomic diversity of the testicular microbiome and the urethral microbiome and its role in the development of infertility in patients with non-obstructive azoospermia against the background of existing varicose veins of the spermatic cord, using the new generation high-throughput sequencing (NGS) method. Materials and methods. From 2020 to 2022, we studied and analyzed the biological material of 11 infertile men with non-obstructive azoospermia and concomitant varicocele. The resulting material of 11 urethral swabs and 10 testicular tissue samples was prepared and taken for further study of the bacterial microbiome using the high-throughput NGS method. Results. Analysis of the studied clinical group clearly demonstrated that the testicular tissue of patients with azoospermia and concomitant varicocele has its own unique microbiome. This may indicate not only taxonomic diversity at the level of both phyla and reads, but also a high degree of significance of impaired function of the blood-testicular barrier (HTB). Сonclusions. The testicular tissue of infertile men with azoospermia and concomitant varicocele has a pronounced diversity of microbiota not only at the level of phyla, but also at the level of reads, which proves the importance of the testicular microbiota in the regulation of spermatogenesis, and also confirms the theory of the initial insufficiency of the hematotesticular barrier against the background of the existing varicose veins of the seminal cord.

Применение рекомбинантного ФСГ в лечении бесплодия, ассоциированного с высоким уровнем фрагментации ДНК сперматозоидов.

Introduction. Male infertility, caused by a high level of sperm DNA fragmentation, remains one of the significant problems of reproductive medicine. One of the methods to overcome it may be the use of recombinant follicle-stimulating hormone (FSH), but the results of studies on this issue are ambiguous. The purpose of this literature review is to systematize publications on this issue. Materials and methods. The search, analysis and systematization of publications in the databases PubMed, eLibrary.ru, Clinicaltrials.gov were carried out using the keywords «male infertility», «sperm DNA fragmentation», «treatment», «follicle stimulating hormone», «FSH». Seventy six publications were selected and included in this review. Results and discussion. The integrity of the genetic material of the sperm is one of the prerequisites for the formation of a normal embryo. Its damage occurs in two main ways: induction of apoptosis and direct damage to DNA by reactive oxygen species. FSH stimulates spermatogenesis and also prevents the induction of spermatozoa apoptosis through the activation of protein kinase B/AKT. Also FSH regulates chromatin packing and increases the ability of spermatozoa to bind to hyaluronic acid. Its use in infertile men led to an improvement in the morphological parameters of spermogram, sperm motility, a decrease in the level of sperm DNA fragmentation, however, the data obtained are difficult to compare due to the heterogeneity of the patient groups included in the study, the lack of standardization of methods for studying the level of sperm DNA fragmentation and using its different threshold values. Conclusions. Therapy with recombinant FSH is one of the promising methods for overcoming infertility in patients with a high level of sperm DNA fragmentation. The heterogeneity of published studies does not allow to draw unambiguous conclusions regarding its effect on the integrity of the genetic material of spermatozoa. Future studies need to use strict inclusion criteria, such as thresholds for the level of sperm DNA fragmentation and the results of a pharmacogenetic study.

No One is Immune to Infertility

Both primary and secondary infertility affects millions of person’s world over. There are several factors that can contribute to infertility in women and men however about 1 in 5 cases of infertility are identified as unexplained. There’s a time frame to fertility in human life span; child bearing age is defined in females but not in males in general. Infertility has significant negative social impacts particularly on women. Infertility is regarded as a negative force in population dynamics because there is no biological replacement, and the continuation of human society. Infertile couples might experience social and psychological distress such as depression, anxiety, social isolation, and sexual dysfunction. Infertile couples suffer from an impaired health-related quality of life. Women in particular are at greater risk of violence, divorce, social stigma, emotional stress, depression, anxiety and low self-esteem. In women, cause of infertility can include endometriosis, uterine fibroids and thyroid disease. Men with fertility problems may have a low sperm count or low testosterone. The risk of infertility increases with age.

Ayurvedic management of Infertility - A Case Report

Infertility is defined as inability to conceive after 12 months of unprotected sexual intercourse. Infertility can be attributed primarily to male factors in 25%, female factors in 58%, and is unexplained in about 17% of couples.[1] It affects millions of people and has an impact on their families and communities. Estimates suggests that approximately one in every six people of reproductive age worldwide experience infertility in their lifetime.[2] Abnormalities in menstrual function constitute the most common cause of female infertility. Other disorders include ovulatory dysfunction, abnormalities of the uterus or outflow tract and psychological stress.[5] In this case study a female patient aged 29 years was unable to conceive since 2 years of marital relationship seeking for Ayurveda line of treatment. From detail history Agnimandya, Ama and stressful condition in work pattern were noticed. She was treated with classical Vamana followed by Shamana treatment. Agnidipana, Amapachana, Vamana, Matra Basti and oral medicines were started. Relaxation technique mediation was advised to the patient. After 2 months the urine pregnancy test was found to be positive and the same was confirmed by ultrasonography.

P-102 Inhibition of RANKL increases the number of motile sperm in a subgroup of infertile men

Abstract Study question Does inhibition of RANKL increase semen quality in infertile men? Summary answer Overall, inhibition of RANKL (Denosumab) did not affect semen quality. However, in a subgroup of men with high serum AMH sperm production was significantly increased. What is known already Currently, there is no treatment available for male infertility, but studies in animal and preclinical human data have suggested a role for RANKL in male reproduction. Study design, size, duration A single-center, double-blinded, randomized clinical trial in 100 infertile men randomly assigned (1:1) to s.c. injection with 60 mg/mL Denosumab or s.c. saline injection 1 mL (0.9%) (placebo). The primary endpoint was changes in semen production, though the study was designed as an explorative study, with the aim of investigating the profile of which infertile men who would have a beneficial treatment outcome of Denosumab. Participants/materials, setting, methods All participants were infertile men referred to our andrological clinic due to impaired semen quality. Blood and semen samples were collected at baseline and after one and two cycles of spermatogenesis on day 80 and day 160, respectively. Main results and the role of chance There were no differences in semen quality or reproductive hormones at day 80 or day 160 between men treated with Denosumab or placebo. However, men with a serum AMH ≥ 40 pmol/L had a significant increase in total motile sperm (143% (SD 116%); p = 0.011), progressive motile sperm (133% (SD 100%); p = 0.039) and a borderline increase in sperm concentration (64% (SD 95%); p = 0.056) at day 80 compared to baseline. Further stratifying men according to both serum AMH (≥ 40 pmol/L) and serum RANKL (highest 50%), showed a significantly higher increase in sperm concentration (107% (SD 111%) vs. -8% (SD 68%); p = 0.009), total motile sperm (256% (SD 270%) vs. 31% (SD 125%); p = 0.039) and progressive motile sperm (191% (SD 194%) vs. 18% (SD 134%) p = 0.013) at day 80 in men treated with Denosumab compared to placebo treated men. Furthermore, serum FSH (-28% (SD 33%) vs. 0%, (SD 22%); p = 0.041) and serum LH (-29% (SD 28%) vs. 20% (SD 51%), p = 0.048) were significantly lower and testosterone/LH ratio (50% (SD 51%) vs. -7% (SD 43%); p = 0.024) significantly higher at day 80 in men treated with Denosumab compared to placebo treatment. Limitations, reasons for caution This is a report from a randomized clinical trial, with an explorative design. Randomized clinical trials in a predefined group of infertile men with high serum AMH, are needed to explore if inhibition of RANKL improves semen quality and pregnancy rate in infertile couples with male factor infertility. Wider implications of the findings The increase in sperm production after Denosumab treatment in infertile men with preserved Sertoli cell function needs to be validated, in a trial selecting men based on serum AMH. Ultimately, Denosumab may be a potential breakthrough in treating male infertility at least in some infertile men with high serum AMH. Trial registration number NCT03030196

P-560 Stigma related to male infertility in China: a scale development and validation study

Abstract Study question Is it possible to develop a trustworthy instrument to evaluate the infertile men's stigma and to document fully all methodological steps, including validation? Summary answer The Male Infertility Stigma Scale (MISS) has been developed to evaluate the stigma status of infertile men with a good reliability and validity. What is known already Infertile men regard childless as a hidden stigma, which influence all the dimensions of their lives and well-being. Most instruments focus exclusively on women and no questionnaires have been directed at infertile men. Study design, size, duration A cross-sectional study was conducted to analyse the validity and reliability of MISS. This was a one-centre study in the Center of Reproductive Medicine of the Third Affiliated Hospital of Guangzhou Medical University between January 2019 to May 2019. Participants/materials, setting, methods This study was carried out on men (n = 432) with a diagnosis and treatment for male-factor infertility. Item generation and reduction of MISS was formed by combining literature review, interviews of experts and patients, and related scale. Exploratory factor analysis (n = 216) and confirmatory factor analysis (n = 216) were performed to indicate the scale constructs. In addition, reliability analyses including internal consistency and test–retest analysis (n = 18)were carried out. Validity was analyzed by convergent validity and content validity. Main results and the role of chance This study developed a 18-item MISS with three dimensions (social marginalization, self-devaluation, psychological insecurity). Exploratory factor analysis indicated that these three dimensions explained 60.14% of total variances.The confirmatory factor analysis showed that the construct of the MISS fitted well with the hypothetical model. The Cronbach's α,split-half coefficient and test–retest correlation coefficient for the whole scale was 0.951, 0.884,and 0.945, respectively. The associations of the MISS with other measure suggested good convergent validity. The Content Validity Index (CVI) was 0.988. Limitations, reasons for caution The reliability and validity of the MISS developed in this study were verified only among the infertility men in Guangzhou and the discriminant validity of dimension 3(psychological insecurity) in this survey was a little poor. The convenience sampling method precluded the validity and generalization of the conclusions. Wider implications of the findings This study may create an effective evaluation measurement to understand the stigma status of infertile men. Future studies should focus on using the MISS in larger samples with different characterizations, such as different areas, and then taking some measures to help them . Trial registration number None

P-566 Is the seminal oxidative stress the mirror of psychological stress perceived by infertile men?

Abstract Study question To assess the association between anxiety and depression scores and the levels of oxidative stress in seminal plasma of Tunisian infertile men. Summary answer Depression in hypofertile men is associated to higher levels of catalase in seminal plasma and thus to oxidative stress. What is known already Within the last decades, the knowledge concerning the link between psychological and oxidative stress in infertile men has been surging. In a limited number of studies aiming to elucidate the psychological aspect of male infertility, data related to increased incidence of depression and anxiety have been reported. It has also been reported that anxiety and depression may trigger the production of reactive free oxygen radicals leading to disruption of the balance between free radicals and antioxidants semen properties. Study design, size, duration This was a cross-sectional study performed in the Laboratory of Cytogenetics and Reproductive Biology of Fattouma Bourguiba University Teaching Hospital (Monastir Tunisia). A total of 282 patients were assessed for levels of anxiety and depression and evaluated for semen parameters. Among these, 105 patients were assessed for levels of superoxide dismutase (SOD) and 51 patients were evaluated for the levels of catalase in seminal plasma from September 2022 to January 2023. Participants/materials, setting, methods Were included patients addressed for semen quality assessment. All patients with a previously diagnosed psychological disorder, those who presented severe depression and/or anxiety symptoms or had a stressful life event were not included. Informed consent was obtained from all the participants. The subjects were evaluated for anxiety and depression symptoms using the valid Arab version of the HAD (Hospital Anxiety and Depression) scale. Semen analysis and results interpretation were performed according to 2021 WHO guidelines. Main results and the role of chance The mean HAD-D (depression) and HAD-A (anxiety) scores were of 6.56 ± 3.07 (IIQ [4-8]) and 7.94 ± 3.73 (IIQ [5-10]) respectively. The mean levels of SOD and catalase were of 42.32 ± 24.08 and 19599.82 ± 12745.36 respectively. The results showed that patients exhibiting elevated HAD-D scores have higher levels of catalase in seminal plasma compared to those with normally ranging HAD-D scores (29856.07±15904.51 VS 17968.14±11564.79 respectively; p= 0.02). However, SOD levels were similar between the two groups and no correlation was found between seminal oxidative stress as assessed by catalase and SOD levels and both HAD-D and HAD-A scores. Limitations, reasons for caution The main limitation reason could be related to the limited number of patients evaluated for levels of catalase in seminal plasma (N = 51). Furthermore, assessing hormone’s levels (LH, FSH and testosterone) would be of great interest in elucidating the implicated pathways leading to oxidative stress and impaired semen quality. Wider implications of the findings Our results shed the light on the elevated levels of the catalase in patients with high depression scores. The absence of correlation between antioxidant enzymes and psychological well-being of infertile patients is a reassuring finding. However, awareness and recognition of depressive symptoms in infertile men is crucial when managing infertility. Trial registration number not applicable

P-086 Prevalence and clinical factors associated with biochemical hypogonadism in infertile men with non-obstructive azoospermia: a single-center cohort study including 761 patients

Abstract Study question What is the prevalence, and which factors are associated with hypogonadism in infertile men with non-obstructive azoospermia (NOA)? Summary answer The prevalence of biochemical hypogonadism among NOA males is significant. The condition is associated with testicular volume, estradiol levels, paternal age, and testicular histopathology results. What is known already NOA is a severe and irreversible condition that accounts for approximately 60% of azoospermia cases, primarily associated with intrinsic testicular deficiencies of various causes. NOA men can present signs of hypogonadism, associated or not with elevated circulating FSH levels; however, the exact prevalence is ill-reported. There is also a lack of data on the clinical factors associated with hypogonadism. We, therefore, estimated the prevalence of biochemical hypogonadism using real-world data and investigated its relationship with clinical factors. Study design, size, duration An observational cohort study was conducted, including 767 consecutive NOA patients with primary spermatogenic failure seeking fertility treatment at a University-affiliated tertiary center for male reproductive health between January 2014 and September 2021. Biochemical hypogonadism was defined as total testosterone (T) levels &amp;lt;350 ng/dL, measured by chemiluminescence immunoassay from a venous sample, collected in the morning, from 8:00 to 10:00 am, and confirmed on a second analysis at least one week apart. Participants/materials, setting, methods All included patients (age range: 23-55 years) had complete clinical, hormonal, genetic, seminal, and histopathology data and were naïve concerning previous sperm retrieval attempts. Patients with NOA due to hypogonadotropic hypogonadism and those using hormonal therapy were excluded. Prevalence rates were computed by Goodman’s method. The relationship between clinical factors and hypogonadism was assessed by logistic regression analysis. We also assessed the frequency of patients with high and within-range FSH levels in the cohort. Main results and the role of chance NOA patients with biochemical hypogonadism represented 80.3% (95% confidence interval [CI] 77.3–43.7) of the studied population. The median (interquartile range [IQR]) of T and FSH levels in hypogonadal men were 276 ng/dL (233.0-303 ng/dL) and 12.3 IU/L (8.9-18.2). Among them, hypergonadotropic (FSH&amp;gt;12 IU/L) and normogonadotropic (within-range FSH levels 1.5-12.0 IU/L) patients were 52.1% (95% CI 48.1-56.0) and 47.8% (43.9-51.8) of studied individuals, respectively. Logistic regression analyses revealed that testicular volume (p &amp;lt; 0.0001) and estradiol levels (p = 0.0005) had a significant inverse relationship with hypogonadism, whereas paternal age (p = 0.02) showed a positive relationship. Moreover, testicular histopathology was a relevant predictor (p = 0.003), with an inverse relationship between hypogonadism and germ cell maturation arrest and a positive relationship between hypogonadism and hypospermatogenesis or Sertoli cell-only. Using these variables, a model constructed to predict hypogonadism had an area under the ROC curve of 0.72. Limitations, reasons for caution Limitations include possible unmeasured confounding factors and the intra- and inter-assay electrochemiluminescence method variability. Another limitation is that the study center is a referral facility for azoospermic patients; thus, hypogonadism prevalence rates reported herein might not represent that of the general population of NOA males attending general fertility centers. Wider implications of the findings Efforts are needed to provide adequate care for this population due to its association with poor quality of life. Moreover, as recent evidence has suggested that hormonal therapy to boost T production might increase sperm retrieval success rates, studies investigating hormonal therapy in such patients may be warranted. Trial registration number Not applicable

P-558 The importance of sexual desire for the sexual health of infertile women and men starting their fertility clinic journey

Abstract Study question Is the sexual desire of infertile women and men correlated with their intercourse frequency and sexual satisfaction? Summary answer Both partner’s sexual desire is moderately correlated to intercourse frequency and their own sexual satisfaction and weakly correlated to the sexual satisfaction of their partner. What is known already Reviews showed that infertile couples have worse sexual health than the general population. Qualitative studies explained that infertile patients feel less attractive and consider intercourse a ‘duty’, associated with failure. Fertility clinics offer diagnosis and treatments but have yet to start caring for sexual health. The Pleasure&amp;Pregnancy-programme, combining psychosexual education with communication, mindfulness and sensate focus exercises, recently proved to increase the sexual desire of infertile women pursuing natural conception. Whether improving sexual desire can be expected to increase the intercourse frequency and sexual satisfaction of women and men about to start fertility treatment had yet to be explored. Study design, size, duration A cross-sectional cohort of 140 heterosexual couples (n = 280; response rate 51%) was surveyed between 2019 and 2022. Couples filled out a package questioning their sexual health over the past four weeks at a chosen moment between their first fertility clinic consultation and the end of their diagnostic workup. This package included a questionnaire to be filled out by each partner individually and a couple questionnaire. Non-responders received were reminded. Participants/materials, setting, methods Sexual desire and satisfaction of women and men was assessed with subscales of the following valid and reliable questionnaires: Female Sexual Function Index in women (FSFI; the higher, the better) or International Index of Erectile Function in men (IIEF; the higher, the better). Intercourse frequency of couples was assessed with a sexual activity event log. Spearman rho’s correlations assessed associations between sexual desire, sexual satisfaction and coital frequency. Main results and the role of chance Responding women and men were in their early thirties and had tried to conceive naturally for 18.2 months, on average. The sexual desire of women (and of men was not correlated (r = 0.116, p = 0.178). Couples had sexual intercourse seven times per month (7.12±4.03), on average. The sexual desire of both women and men was moderately correlated to couple’s intercourse frequency (♀: r = 0.402, p &amp;lt; 0.001; ♂: r = 0.426, p &amp;lt; 0.001). The sexual desire of women was also moderately correlated to their own sexual satisfaction (r = 0.481, p &amp;lt; 0.001) and weakly correlated to the sexual satisfaction of their male partner (r = 0.270, p = 0.001). The sexual desire of men was significantly but weakly correlated to their own sexual satisfaction (r = 0.361, p &amp;lt; 0.001) and the sexual satisfaction of their female partner (r = 0.239, p = 0.005). Limitations, reasons for caution The sexual health of the included couples is currently followed-up during fertility treatment. Linear mixed models, taking account of dyads and of multiple assessments, would allow analysing the impact over time of women’s sexual desire whilst taking account of the sexual desire of her male partner and vice-versa. Wider implications of the findings Sexual desire seems important for a couple’s coital frequency and both partner’s sexual satisfaction. Examining whether a six-month sexual health programme that improves women’s sexual desire, could in the longer term improve intercourse frequency and especially sexual satisfaction or prevent the deterioration thereof would be interesting. Trial registration number not applicable

O-299 Sperm DNA fragmentation by TUNEL influences live birth in egg recipients after euploid embryo transfer

Abstract Study question Does sperm DNA fragmentation (SDF) by TUNEL affect reproductive success measured as live birth rate (LBR) in egg recipients after euploid embryo transfer? Summary answer SDF increases miscarriage rates in egg recipients with PGT-A. Therefore, live birth rates depends on sperm DNA damage in egg recipients after euploid embryo transfer. What is known already Sperm DNA integrity is important for optimal fertilisation, implantation and pregnancy. Although controversial, several studies have shown that sperm DNA fragmentation correlates with adverse pregnancy outcomes in infertile men. Ooplasmic sperm DNA fragmentation repair mechanisms may occur in female gametes, mainly in young women. However, research on the impact of DNA fragmentation on LBR are limited. Also, chromosomally normal embryos analysed by PGT-A offers opportunity to isolate female factor and study male factor. The aim of this study is to assess whether high level of semen DNA damage has an impact on reproductive outcomes in terms of live birth rate. Study design, size, duration This is a retrospective study of 467 PGT-A cycles in egg recipients. The study population consists of infertile couples for euploid embryo transfer (February 2017-November 2022). Semen samples were obtained to measure DNA damage from 447 men. PGT-A was performed in 1831 blastocysts. Trophectoderm biopsies (d5/d6 blastocysts) were analysed by NGS (Veriseq Illumina). Embryos were frozen and 568 blastocysts transferred in the subsequent cycle. Conventional hormone replacement was used for endometrial preparation in recipient patients. Participants/materials, setting, methods Cohort study with 447 infertile couples attending to private fertility clinic undergoing ART with their autologous semen, donated oocytes and PGT-A. SDF was measured by Terminal-deoxyribonucleotidyl-ARTSferase-mediated dUTP Nodule End Labelling (TUNEL) assay using the FITC-labelled-dUTP in situ cell death detection kit (Roche). The cohort was divided into two groups according the DNA fragmentation index (DFI): high SDF group (DFI&amp;gt;20%) and normal SDF group (DFI≤20%). To evaluate reproductive outcomes Chi-square and Linear regression tests were used. Main results and the role of chance Of the 447 couples included (average paternal age 41.29 + 7.32 years), 66.5% of male partners had normal semen parameters. We reported high sperm DNA fragmentation in 8% of patients. Overall, the embryo aneuploidy rate was 31.7%. For the further statistical analysis confounding factors such as, female and male age, embryo quality, day of embryo biopsy were included. PGT-A analysis showed an aneuploidy rate of 32.1% in the high DNA fragmentation group and 30.3% in the normal DNA fragmentation group (p = 0.453). Regarding clinical data, the overall implantation rate was 34.9%. There was no significant difference between elevate DNA fragmentation and normal DNA fragmentation with respect to biochemical miscarriage rate (4.3% vs 7.6%, p = 0.799). Although not significant differences between groups, a lower implantation rate near to reach significance was found in the high SDF group (20.0% vs 34.4%, p = 0.050). Pregnancy and clinical pregnancy rates were significantly lower in the high DNA fragmentation group (26.1% vs 44.9%, p = 0.042; 21.7% vs 31.3%, p = 0.044;), respectively. Also, miscarriage rate was significantly higher in the high SDF group (40% vs 12.5%, p = 0.014). Therefore, the live birth rate was significantly lower in the high SDF group (13.0% vs 32.6%, p = 0.024). Limitations, reasons for caution Larger studies including a higher number of samples are needed to confirm the correlation observed between LBR in eggs recipients with semen DNA fragmentation. Those patients with a DFI higher than control values should be treated with antioxidants. The pregnancy outcomes should be analyzed after treatment of DNA fragmentation. Wider implications of the findings Our findings suggest that autologous semen DNA fragmentation influence in live birth rate in egg recipients. Our data show that live birth rates decreased in patients with a high DFI after PGT-A. This study confirms published studies in the literature showing that ART outcomes are affected by sperm DNA fragmentation. Trial registration number Not Applicable

P-065 A systematic review of the accuracy of laboratory semen analysis as a test of fertility

Abstract Study question Which semen parameters are predictive of treatment-dependent and treatment-independent reproductive outcomes? Summary answer Progressive motility predicted treatment-independent pregnancy, total motile sperm count (TMSC) predicted failed fertilisation with IVF and pregnancy following IUI, and morphology predicted pregnancy after IUI. What is known already Semen analysis, an essential component of any fertility work-up, is useful in identifying azoospermia and oligozoospermia, but its discriminatory capacity to identify fertile and infertile men has been questioned, including by the World Health Organisation (WHO). It has also been suggested that a combination of semen parameters has better predictive value than a single parameter. We conducted a systematic review of the literature to determine the association between different semen parameters and spontaneous (treatment-independent) pregnancy outcomes, as well as pregnancy outcomes following various fertility treatments (treatment-dependent outcomes). Study design, size, duration A protocol was registered prospectively with PROSPERO (CRD42021251988). A systematic search of MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials was undertaken to include papers published from 1st January 2000 to 25th May 2021. Studies were not limited by language. Two reviewers independently screened the search results and undertook data extraction. Risk of bias assessment was undertaken with the QUADAS-2 or QUIPS tool, depending on study design. Participants/materials, setting, methods Studies were eligible if they included men undergoing semen analysis for any indication and reported the accuracy of one or more semen analysis parameters in predicting treatment-dependent or treatment-independent reproductive outcomes – these included fertilisation rate, clinical pregnancy, live birth, and time to pregnancy. Studies were excluded if semen analysis was not the primary test being assessed or no reproductive outcomes were reported. Main results and the role of chance Of 5236 publications and 139 full-text articles, 62 studies were included. 52 studies reported treatment-dependent outcomes and 10 reported treatment-independent outcomes. Most treatment-dependent studies lacked key information and were rated as unclear risk of bias in at least one domain (79.3% overall). Half of the treatment-independent studies were high risk of bias in at least one domain. Of all semen parameters, progressive motility and sperm concentration predicted treatment-independent pregnancy outcomes. Three studies concluded progressive motility predicted pregnancy rates at a range of thresholds (threshold 24%: area under the curve (AUC) 0.909; &amp;lt;32% vs ≥ 32%: adjusted odds ratio (aOR) 4.2 (95% CI 1.1-15) and &amp;lt;50% vs ≥ 50%: aOR 2.8 (95% CI 1.3-6.1); per 10% reduction in progressive motility, pregnancy chances reduced by 11%: hazard ratio (HR) 0.89 (95% CI 0.85-0.93)). Sperm concentration predicted pregnancy within 6 months (≥20 vs &amp;lt; 20 million/ml, adjusted rate ratio 0.68 (95% CI 0.52-0.91)) and 12 months (adjusted HR 1.35 (95% CI 1.09-1.66)). In those undergoing IUI, pre-/post-wash TMSC and morphology predicted pregnancy, but with no clear threshold values. TMSC predicted “total fertilisation failure” in an IVF population (AUC 0.631-0.75). In an ICSI population, no semen parameter predicted fertilisation rate, pregnancy, or live birth rate. Limitations, reasons for caution Meta-analysis was not possible due to a wide range of cut-off values used for each semen parameter. Due to the low quality of the evidence included, poorly detailed female populations, and WHO manual methods often not being used for reporting, the findings of this review should be viewed with caution. Wider implications of the findings Whilst this review has identified certain semen parameters in isolation are predictive of pregnancy in treatment-dependent and treatment-independent scenarios, clear threshold values have not been identified. This questions the reporting of morphology as it is labour intensive to assess and is only predictive of pregnancy in a population having IUI. Trial registration number Not applicable

A novel frameshift mutation in DNAH6 associated with male infertility and asthenoteratozoospermia.

Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a considerable genetic heterogeneity underlying asthenoteratozoospermia. In this study, we performed a genetic analysis of two brothers from a consanguineous Uighur family in China to identify gene mutations causative for asthenoteratozoospermia-related male infertility. Two related patients with asthenoteratozoospermia from a large consanguineous family were sequenced by whole-exome sequencing and Sanger sequencing to identify disease-causing genes. Scanning and transmission electron microscopy analysis revealed ultrastructural abnormalities of spermatozoa. Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence (IF) analysis were used to assess the expression of the mutant messenger RNA (mRNA) and protein. A novel homozygous frameshift mutation (c.2823dupT, p.Val942Cysfs*21) in DNAH6 was identified in both affected individuals and was predicted to be pathogenic. Papanicolaou staining and electron microscopy revealed multiple morphological and ultrastructural abnormalities of affected spermatozoa. qRT-PCR and IF analysis showed abnormal expression of DNAH6 in affected sperm, probably due to premature termination code and decay of abnormal 3' untranslated region (UTR) region of mRNA. Furthermore, intracytoplasmic sperm injection could achieve successful fertilization in infertile men with DNAH6 mutations. The novel frameshift mutation identified in DNAH6 may contribute to asthenoteratozoospermia. These findings expand the spectrum of genetic mutations and phenotypes associated with asthenoteratozoospermia and may be useful for genetic and reproductive counseling in male infertility.