Male Factor Infertility Research Articles

Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial.

Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF? Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38 years old with an established IVF history of POR. POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention. This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022. Patients who met inclusion criteria (<38 years old, two or more prior cycles with <3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35 kg/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Müllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval. In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n = 41) or to no intervention (n = 42). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8 ± 2.4 vs 3.1 ± 3.3 in PRP vs control, respectively; P = 0.9), blastocysts (1.0 ± 1.3 vs 1.3 ± 2.1, P = 0.8), or euploid blastocysts (0.8 ± 1.1 vs 0.9 ± 1.6; P = 0.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P = 0.4; relative risk [RR], 95% CI = 0.9, 0.6-1.2) or the rate of sustained implantation (31% vs 29%, P = 0.9; RR 1.0, 0.7-1.3). Posttreatment AFC (7.9 ± 4.5 vs 6.8 ± 4.8, P = 0.3) and AMH (0.99 ± 0.98 vs 0.7 ± 0.6, P = 0.2) were also not different between the groups. Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI. The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38 years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population. Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare. Clinicaltrials.gov Registry Identifier: NCT04163640. 15 November 2019. 24 February 2020.

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence.

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.

Assessment of a Decade of Change in U.S. Assisted Reproductive Technology Cumulative Live-Birth Rates: 2004-2009 Compared With 2014-2020.

To assess the effects of demographic shifts, changes in contemporaneous clinical practices, and technologic innovation on assisted reproductive technology (ART) success rates by conducting an analysis of cumulative live-birth rates across different time periods, age groups, and infertility diagnoses. We conducted a retrospective cohort study of autologous linked cycles comparing cumulative live-birth rates over successive cycles from patients undergoing their first retrieval between 2014 and 2019 in the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) database. All cycles reported for these individuals up to 2020 were included for analysis. We compared cumulative live-birth rates stratified by age and infertility cause with published data from the 2004-2009 SART CORS database. From 2014 to 2019, 447,042 patients underwent their first autologous index retrieval, resulting in 1,007,374 cycles and 252,215 live births over the period of 2014 to 2020. In contrast, between 2004 and 2008, 246,740 patients underwent 471,208 cycles, resulting in 140,859 births by 2009. Noteworthy shifts in demographics were observed, with an increase in people of color seeking reproductive technology (57.9% vs 51.7%, P <.001). There was also an increase in patients with diminished ovarian reserve and ovulatory disorders and a decrease in endometriosis, tubal, and male factor infertility ( P <.001). Previously associated with decreased odds of live birth, frozen embryo transfer and preimplantation genetic testing showed increased odds in 2014-2020. Preimplantation genetic testing rose from 3.4% to 36.0% and was associated with a lower cumulative live-birth rate for those younger than age 35 years ( P <.001) but a higher cumulative live-birth rate for those aged 35 years or older ( P <.001). Comparing 2014-2020 with 2004-2009 shows that the overall cumulative live-birth rate improved for patients aged 35 years or older and for all infertility diagnoses except ovulatory disorders ( P <.001). This analysis provides insights into the changing landscape of ART treatments in the United States over the past two decades. The observed shifts in demographics, clinical practices, and technology highlight the dynamic nature of an evolving field of reproductive medicine. These findings may offer insight for clinicians to consider in counseling patients and to inform future research endeavors in the field of ART.

Association between embryo morphokinetic development and intracytoplasmic sperm injection with epididymal sperm via time-lapse imaging.

The objective of this study was to investigate the impact of sperm source on embryo morphokinetics and the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles by considering the clustering of data (multiple embryos per patient that share a comparable developmental timing). This matched cohort study was performed at a private university-affiliated in vitro fertilization center. Women who underwent ICSI with epididymal sperm between January 2019 and December 2020 (the percutaneous epididymal sperm aspiration group, n = 32 cycles) were matched with women who underwent ICSI with ejaculated sperm because of idiopathic male factor infertility (the male factor infertility [MFI] group, n = 32 cycles) or female infertility (the control group, n = 32 cycles). Embryos were cultured in a time-lapse imaging incubator, and morphokinetic development was recorded and compared among the groups. Significantly slower divisions were observed in embryos derived from epididymal sperm than in those derived from the MFI and control groups. Embryos derived from epididymal sperm had a significantly lower KIDScore (3.1 ± 0.2) than did those derived from ejaculated spermatozoa from the MFI (5.4 ± 0.1) and control (5.6 ± 0.2, p < 0.001) groups. Epididymal sperm-derived embryos showed a significantly greater occurrence of multinucleation (23.2%) than did those derived from ejaculated sperm from the MFI and control groups (2.8% and 3.7%, p < 0.001, respectively). Epididymal sperm-derived embryos were significantly more likely to undergo direct or reverse cleavage (11.1%) than ejaculated sperm-derived embryos in the control group (4.3%, p = 0.001). In conclusion, delayed cell cleavage and increased incidences of blastomere multinucleation and abnormal cleavage patterns are observed when epididymal-derived sperm are used for ICSI.

Comparative evaluation of visual-palpatory findings with scrotal doppler ultrasound data for varicocele diagnosis

Introduction. Current evidence suggests that management of any grade of varicocele can improve male fertility. However, diagnosis of grade 1 varicocele in infertile men without the use of scrotal Doppler ultrasound may cause overtreatment.Objective. To study the comparability and accuracy of the visual palpatory examination method with the scrotal Doppler ultrasound data for the diagnosis of varicocele.Material &amp; methods. Between November 2005 to January 2022, 2871 patients diagnosed with varicocele and infertility who underwent microsurgical varicocelectomy by inguinal access were examined at RSSPMCU. The average age of the patients was 30.16 ± 0.09 (18 – 60) years. Of the 2871 patients, 2592 (90.3%) were diagnosed by physical examination, and 279 (9.7%) patients underwent additional scrotal Dopper ultrasound.Results. After Doppler scrotal imaging was introduced into practice, the proportion of patients with bilateral varicocele increased from 32.2% to 61.6% (p &lt; 0.01). The proportion of patients with right-sided varicocele also increased significantly. Experienced physicians during physical examination of infertility patients did not diagnose grade 1 varicocele in 4.3%.Conclusions. The implementation of scrotal Doppler ultrasound for the diagnosis of male infertility improved the detection of grade 1 varicocele and bilateral varicocele. In turn, this contributed to earlier elimination of the male factor of infertility in this contingent of patients.

Preventable Male Infertility: Identifying the Modifiable Risk Factors

Background: Infertility is a global health issue, with both genders having equal contribution. Approximately 15% of couples having difficulty to conceive after one year of consistent, unprotected sexual activity, infertility. Objectives: To identify the modifiable risk factors of male infertility in patients visiting a private hospital of Peshawar.Material and Methods: The study was a descriptive Cross-sectional of six months duration. A total sample size of 733 married male patients visiting private hospital were included and those who were reluctant to participate were excluded. Structured questionnaire were filled. Non probability convenience sampling technique was used and data was analyzed using SPSSversion 22Results: Out of 733 sample size 397(54%),336 (45.9%) had secondary and primary infertility, respectively. Risk factors, like obesity, smoking, diabetes mellitus, congenital anomalies and varicocele were linked to infertility with p valve &lt; 0.05. The majority 568 (77.5%) had normal semen count, Oligospermia and Azoospermia were 11%.Conclusion: Our study concluded that smoking, diabetes mellitus, obesity, semen abnormalities and congenital anomalies were related to both primary and secondary infertility among men in Peshawar.Keywords: Male infertility, Obesity, Risk factors, Semen analysis, Semen abnormalities, Tobacco use.

Machine learning approach to assess the association between anthropometric, metabolic, and nutritional status and semen parameters.

Many lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.

A Study on Impact of Smoking on Semen Parameters

Introduction: Infertility approximately affects 15% of couple in India, among which male factor infertility isassociated as contributing factor causing infertility in 40- 50% of cases and sole cause in 15 -20% of cases. Semen analysis is a standard investigating tool in evaluating male infertility. Lifestyle factors namely diet, obesity, smoking, alcohol, stress, play a major role in health. Among these factors smoking is inevitable, causing detrimental effects on semen parameters and associated with lower fertility rates.Methodology: A cross sectional study was conducted among 295 male partners of women with infertility,attending the fertility Clinic, in reproductive medicine department over 10 months. Two hundred andninety five men satisfying the inclusion and exclusion criteria were selected by simple random sampling technique. The semen parameters of the participants were analysed, entire socio-demographic profile and detailed history was obtained using structured questionnaire and confidentiality was maintained. The results were ascertained using SPSS.Results: Among 295 participants, total 99 (33.55%) men had abnormal semen parameters. Nearly half of thestudy subjects (i.e.) 148 (50%) among 295 subjects were found to be smokers. Among 99 male with abnormalsemen parameters, 60 (61%) men who had abnormal semen parameters were smokers. This study proves a strong association between smoking on male fertility (1.9 times greater risk among smokers). Significant association (x 2 = 6.492, p = 0.0108) was found between smoking, reduced semen parameters and quality.Conclusion: Lifestyle modifications such as cessation of smoking, premarital and pre-conception health checkups, counselling, voluntary fertility testing by male partners, early detection and appropriate intervention the saves the reproductive potential. Men must be health educated for developing knowledge on ill effects of smoking, positive attitude, behavioural change and accept his responsibility for strengthening and caring his female partner amidst the societal pressures. Thus the present study substantiates more evidence to the existing literature.

Incidental seminoma in nonobstructive azoospermia: a case report

To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction. Case report. A single patient diagnosed with nonobstructive azoospermia underwent microdissection testicular sperm extraction, and an incidental finding of invasive seminoma was made upon histopathological analysis. 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. 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.

Outcomes of female reproductive performance with assisted reproductive techniques after recent mild to moderate COVID-19 infections: An observational study.

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. 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). 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. 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.

Bacterial Zoonotic Diseases and Male Reproduction

Bacterial zoonotic diseases hold significant public health importance due to their substantial contribution to human morbidity and mortality. These infections have been implicated in reducing the fertility rate among couples of reproductive age. Despite the increasing prevalence of infertility and sub-fertility in men, there has been limited investigation into the possible effects of bacterial zoonotic infections on the male reproductive system. The purpose of this review is to describe common bacterial zoonotic diseases and their effects on human reproduction in order to unveil the hidden roles these infections could play in male factor infertility. While there is a dearth of information on this subject from human studies, available evidence from experimental animals suggests that bacterial zoonotic diseases impair male reproductive functions and structures primarily through the activation of the inflammatory response and distortion of the antioxidant system, resulting in the generation of oxidative species. In light of the limited research on bacterial zoonotic diseases and their role in male reproduction, efforts must be directed towards the subject to unravel the underlying pathological mechanisms and reduce the incidence among the human populace, either through preventive or curative measures.

Microfluidic sperm sorting selects a subpopulation of high-quality sperm with a higher potential for fertilization.

Is a microfluidic sperm sorter (MSS) able to select higher quality sperm compared to conventional methods? The MSS selects sperm with improved parameters, lower DNA fragmentation, and higher fertilizing potential. To date, the few studies that have compared microfluidics sperm selection with conventional methods have used heterogeneous study population and have lacked molecular investigations. The efficiency of a newly designed MSS in isolating high-quality sperm was compared to the density-gradient centrifugation (DGC) and swim-up (SU) methods, using 100 semen samples in two groups, during 2023-2024. Semen specimens from 50 normozoospermic and 50 non-normozoospermic men were sorted using MSS, DGC, and SU methods to compare parameters related to the quality and fertilizing potential of sperm. The fertilizing potential of sperm was determined by measurement of phospholipase C zeta (PLCζ) and post-acrosomal sheath WW domain-binding protein (PAWP) expression using flow cytometry, and the chromatin dispersion test was used to assess sperm DNA damage. In both normozoospermic and non-normozoospermic groups, the MSS-selected sperm with the highest progressive motility, PLCζ positive expression and PLCζ and PAWP fluorescence intensity the lowest non-progressive motility, and minimal DNA fragmentation, compared to sperm selected by DGC and SU methods (P < 0.05). The major limitations of our study were the low yield of sperm in the MSS chips and intentional exclusion of severe male factor infertility to yield a sufficient sperm count for molecular experiments; thus testing with severe oligozoospermic semen and samples with low count and motility is still required. In addition, due to ethical considerations, at present, it was impossible to use the sperm achieved from MSS in the clinic to assess the fertilization rate and further outcomes. Our research presents new evidence that microfluidic sperm sorting may result in the selection of high-quality sperm from raw semen. This novel technology might be a key to improving clinical outcomes of assisted reproduction in infertile patients. The study is funded by the Iran University of Medical Sciences and no competing interest exists. N/A.

Anxiety, Depression, and Quality of Life Among Infertile Women: A Case-Control Study.

Introduction Pregnancy holds significant cultural and social value for women. However, women facing challenges in conceiving often grapple with emotional distress, including depression and anxiety. The connection between psychological elements (stress, anxiety, and depression) and infertility is complex, influenced by multiple factors, and bidirectional. Infertile women are more likely to develop mental illnesses, marital dissatisfaction, and impaired quality of life compared to the individuals of the fertile group. Thus, the study aimed to assess levels of anxiety, depression, and quality of life among infertile women compared to fertile women. Methods This case-control study conducted at a tertiary care center recruited 100 nulliparous women between the age group of 20 and 38 years with primary or secondary infertility, while those with male factor infertility were excluded. The control group (N=100) comprised normal parous women who had at least one child. The primary objective of the study was to assess the impact of infertility on the mental health and quality of life of women seeking infertility treatment. Outcome measures included standardized tools such as the WHOQOL-BREF questionnaire to assess the quality of life across multiple domains (e.g., physical, psychological, social, and environmental) as well as the Depression Anxiety and Stress Scale (DASS-21) to measure levels of anxiety, depression, and stress. Cronbach's alpha was used to measure the tool's reliability. A P value of <0.05 was considered statistically significant. Results Baseline sociodemographic parameters were comparable between the two groups. The mean age of infertile women was 30.6±3.9 years compared to 31.5±3.2 years in fertile women (P=0.076). Using the WHOQOL-BREF scale, we found that the quality of life was better in the fertile group compared to the infertile group through all the physical, psychological, social, and environmental domains (P<0.001). The infertile group had a significantly higher number of women with anxiety, depression, and stress. The questionnaires showed high internal reliability. Conclusion Infertile women experienced a lower quality of life in various domains, higher levels of anxiety, and increased rates of depression compared to fertile counterparts. The study findings underscore the multidimensional impact of infertility, emphasizing the need for comprehensive healthcare approaches to address the psychosocial challenges faced by women undergoing infertility treatment.

Decreased AdipoR1 signaling and its implications for obesity-induced male infertility

Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet. Moreover, we demonstrate that testes weight, sperm count, sperm motility and sperm fertilizing ability were significantly decreased in AdipoR1 knockout mice compared to those in wild-type mice; furthermore, the phosphorylation of AMPK was decreased, and the expression of pro-apoptotic genes and proteins, caspase-6 activity and pathologically apoptotic seminiferous tubules were increased, in the testis from AdipoR1 knockout mice. Furthermore, study findings show that orally administrated AdipoRon decreased caspase-6 activity and apoptotic seminiferous tubules in the testis, thus ameliorating sperm motility in male mice fed a high-fat diet. This was the first study to demonstrate that decreased AdipoR1/AMPK signaling led to increased caspase-6 activity/increased apoptosis in the testis thus likely accounting for male infertility.

1-DNJ Alleviates Obesity-Induced Testicular Inflammation in Mice Model by Inhibiting IKKβ/ NF-kB Pathway

Obesity is associated with chronic inflammation that affects various organs in the body, including the reproductive system, which is a key factor in male infertility. 1-Deoxynojirimycin (1-DNJ) is a natural alkaloid in mulberry leaves, which has anti-inflammatory capabilities, yet, it’s effects on obesity-induced inflammation-related male infertility remain unclear. Therefore, this research investigates the underlying mechanism by which 1-DNJ may mitigate fertility impairment in male mice caused by obesity-related inflammation. Male mice with high-fat diet (HFD)-induced obesity were treated with 1-DNJ or metformin for 8 weeks. Metabolic profiles were evaluated by enzyme method. Reproductive capacity was assessed by sperm viability, motility and counts, immunohistochemistry was performed to evaluate the testicular damage caused by obesity and inflammation. The inflammation was assessed by measuring the levels of tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and interleukin 6 (IL-6). The activation of IκB kinase β (IKKβ) and nuclear factor κB (NF-κB) was examined using western blot and immunohistochemistry. HFD induced obesity in mice with obvious lipid metabolism disorder. The obese male mice had a decreased testosterone level, impaired sperm motility, and increased inflammatory factors. 1-DNJ treatment improved the testosterone level in the obese mice, ameliorated the testicular structure damage and improve sperm viability. In addition, 1-DNJ treatment inhibited IKKβ/NF-kB signaling pathway and reduced inflammation in obese mice. 1-DNJ can improve the fertility of obese men by reducing obesity as well as obesity-induced inflammation. These findings provide new insights for 1-DNJ to alleviate inflammation caused by obesity and provide future possibilities for treating male infertility.

(033) Artificial Intelligence ChatGPT and GPT4 Performance on Male and Female Sexual Dysfunction, Sexually Transmitted Infection, and Male Factor Infertility in the 2019 to 2023 American Urological Association Self-Assessment Study Programs

Abstract Introduction Large Language Model (LLM) applications in Medicine are increasing. Chatbots ChatGPT and GPT4 were tested against medical exams. The vetting of these tests as a source of information for both the patient and physician is needed. A credible source of medical information may be used as the gold standard against which the LLM can be tested. Objective We assess the performance of ChatGPT and GPT4 to answer the American Urological Association (AUA) Self-Assessment Study Program (SASP) questions on male sexual dysfunction (MSD), female sexual dysfunction (FSD), sexually transmitted infection (STI), and male factor infertility (MFI). We aim to find out how credible this LLM is as a source of medical advice. Methods Four registered users of the SASP identified the questions using open book mode in tests from 2019 to 2023, spanning their subscriptions. The questions were ranked for difficulty on a five-point Likert scale. OpenAI ChatGPT 3.5 and GPT4 were used to answer the questions. The GPT program was set to turn off chat history. No plug-ins or feedback were permitted. Prompts were generated from question stems masking question ID and adding the phrase "I am a urologist preparing for my board exam. Please answer the following question:" Images were deleted from questions and substituted with a brief description. All questions were answered separately, first using GPT-4 and then ChatGPT. Three consecutive responses were generated for each prompt, and the consensus answer was tallied. Answers were compared between GPT and provided answer key of SASP. Descriptive statistics, chi-Pearson Chi-square, and Fisher's exact tests were applied. Results We identified 115 questions in the domains of sexual dysfunction, STI, and MFI. Only one question had an associated image. GPT4 performed better than ChatGPT in all domains, providing correct answers of 60% versus 40% (p=0.000). A total of 89.9% of correct answers were three times unanimously regenerated by GPT4 (p=0.007) and 67.4% by ChatGPT (p=0.244). Within each domain, there was no significant difference in the correct answers for each chatbot (Table-1) or test year (p=0.682). The SASP source reference answers were Campbell's Urology only in 38.3 %, AUA guidelines only in 17.4%, AUA core curriculum only in 10.4%, and combinations with other sources in 33.9%. There was no significant association of source reference with the correct answers of GPT4 (p=0.058) or ChatGPT (p=0.451). Only 19.1% were open-access sources, 20% were partially open-access, and 60.9% were restricted to subscribers. The availability of the source did not significantly affect the correct answers of GPT4 (p=0.272) or ChatGPT (p=0.231). Both chatbots' correct answers were associated significantly with easier questions (Table-2). Conclusions The LLM tested has an average accuracy as a source of credible medical information on Sexual dysfunction, STI, and MFI. GPT4 performs better than ChatGPT, especially when there is a unanimous regenerated response. The development of a better model to serve a broader group of physicians and patients will require training of the chatbot on credible urology literature that includes the currently 81% restricted sources. Disclosure No.

(203) Impact of Smoking on Sperm Chromatin Integrity

Abstract Introduction Semen analysis is an essential component of infertility evaluation, but it may still fail to detect subtle sperm defects present in patients with male factor infertility. Although estimates vary, approximately 15% of patients with male factor infertility have normal spermiograms It is necessary to identify diagnostic measures for male infertility that are easy to perform, inexpensive, and provide an accurate diagnosis. Tests that assess sperm quality should not only identify the ability of spermatozoa to reach the oocyte but also their ability to fertilize the oocyte and activate embryo growth. The estimation of sperm DNA damage fills the above need in the diagnosis of male infertility Abnormalities in the male genome characterized by damaged sperm DNA may be indicative for male subfertility regardless of routine semen parameters, and these parameters do not reveal sperm DNA defects Men with normal semen analysis may also have a high degree of DNA fragmentation, which can be a major cause of undiagnosed/unexplained infertility. Sperm DNA fragmentation may result from aberrant chromatin packaging during spermatogenesis, defective apoptosis before ejaculation or excessive production of reactive oxygen species (ROS) in the ejaculate. Objective To study the impact of cigarette smoking on sperm chromatin integrity in infertile patients. Methods The present study included eighty infertile male patients recruited from the Andrology Outpatient Clinic at Al-Azhar University Hospitals The patients were divided into two groups: - Group I: forty nonsmoker infertile males. (Control Group). Group II: forty cigarette smoker infertile males. (Study Group) Results The current study revealed that smoking increases the abnormality of sperm chromatin integrity in sperms of smokers. This is evident by the positive correlation of increased head stainability of sperms in smokers compared to nonsmokers. The value of partially stained sperm heads using aniline blue is calculated from the total staining score formula, this score was found to increase significantly among smokers in comparison to nonsmokers. In the present study, the increased severity of smoking (smoking index), was not correlated with the degree of sperm head stainability. This mean that, smoking insult on sperm chromatin integrity is crucial regardless the duration or the amount of the consumed cigarettes Conclusions There is a significant increase of sperm chromatin damage in smoker infertile patients than nonsmoker infertile patients and these damages may affect the quality of the ejaculated spermatozoa and decrease their fertility potential. Not only semen parameters but also sperm chromatin condensation is affected significantly by smoking. Aniline blue staining is an effective and inexpensive tool for assessment of the fertilization potentiality of infertile patients. A significant correlation was found between the percentage of spermatozoa with normal sperm chromatin condensation and normal morphology. Cigarette smoking may have a negative impact on sperm quality and DNA integrity. Therefore, it would be advisable for men to abstain from smoking to avoid decreased fertility. Disclosure No.

Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative

Abstract Background: Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings. Further, few studies examined associations by ovarian cancer histotypes or were able to disentangle the influence of infertility vs. fertility treatment. Differences across studies could also have been influenced by different study populations (e.g., population-based vs. clinical population/registry of in-vitro fertilization [IVF]) and lack of consistent statistical control for important confounding factors including nulliparity, number of pregnancies, and age at first pregnancy. Finally, prior prospective studies have had limited follow-up, thus not capturing cancers that occur after menopause and which may have different risk factor profiles. Our objective was to determine the association between history of infertility and risk of postmenopausal ovarian cancer in a population that had not received treatment with IVF. Methods: We utilized the Women’s Health Initiative (n=114,761) with over 25 years of follow-up. At study baseline participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of incident ovarian cancer comparing participants with a history of infertility to parous participants without infertility. Logistic regression models were used to calculate odds ratios (OR) for prevalent ovarian cancer at study baseline. Results: Approximately 16% of participants reported a history of infertility. 1,376 participants reported prevalent ovarian cancer at study baseline and 852 cases of ovarian cancer were diagnosed during study follow-up. In the prospective analyses, no statistically significant association was observed between infertility and risk of ovarian cancer overall (HR=1.16; 95% CI=0.98-1.37), by histotype, or with any specific infertility diagnoses. When prevalent ovarian cancer was examined, those reporting a history of infertility had a greater odds of ovarian cancer diagnosis (1.34; 95% CI=1.13-1.58) at WHI cohort baseline. This association was present for most infertility diagnoses with the strongest associations for hormonal/ovulatory (OR=1.97;95% CI=1.24-3.12), tubal/uterine factor (OR=1.63; 95% CI=1.15-2.31), and male factor (OR=1.71; 95% CI=1.19-2.47) infertility. Conclusions: We observed no significant association between infertility history and incident ovarian cancer in our population of postmenopausal participants. An association between infertility and ovarian cancer was present when prevalent ovarian cancer cases were examined, consistent with prior analyses that show stronger associations between ovarian cancer risk factors and ovarian cancer among younger women. Citation Format: Holly Harris, Kimberly Lind, Cynthia Thomson, Nazmus Saquib, Aladdin Shadyab, Peter Schnatz, Rogelio Robles-Morales, Lihong Qi, Howard Strickler, Denise Roe, Leslie Farland. History of infertility and risk of ovarian cancer in the women’s health initiative [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A042.

(271) Assessment of Varicocele Bilaterality in Infertile Men

Abstract Introduction Varicocele is the most common correctable cause of male factor infertility. It has always been a debatable subject as regard how it affects fertility and the best way to treat. However, there is a wide consensus nowadays that varicocelectomy improve male fertility potentials. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. Objective The primary outcome measure was to assess disease bilaterality and the secondary outcome measure was to report on improvement in semen 3 and 6 months post varicocelectomy and pregnancy rate 1 year post surgery. Methods This prospective study was conducted between January 2019 and January 2022. Infertile males with varicoceles underwent microsurgical subinguinal varicocelectomy by expert uroandrologists. Patients who were referred as unilateral varicoceles had their CDUS repeated for assessment of missed concomitant contralateral varicocele. Then, patients who were diagnosed with bilateral varicoceles underwent bilateral subinguinal ligation straight away. Those who were referred with unilateral varicocele had their palpable sides operated on first; then the contralateral side was also explored using an intraoperative Doppler device and the maximal vein diameter was measured. Patients came for follow for at least 6 months after surgery to evaluate any complications and assess improvement in semen parameters. Gynecologists also reported on normal pregnancy rate 1 year after surgery. Results A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). This is statistically significantly higher than initial US (P&amp;lt;0.001). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter [r=0.9, P&amp;lt;0.001]. Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Conclusions Varicocele bilaterality is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome. Disclosure No.

Outcome of intrauterine insemination in couples with unexplained or male factor infertility at National Referral Hospital of Bhutan

Objectives: Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) is the only facility offering intrauterine insemination (IUI) services in the country. In this study, we aim to study the success rate of IUI for the year 2022. Material and Methods: This retrospective study utilized secondary data extracted from the medical records of a cohort of 57 patients who underwent IUI procedures at the infertility clinic between January and December 2022. Ethical clearance and site approval were obtained from the Institutional Review Board at Khesar Gyalpo University of Medical Sciences of Bhutan and JDWNRH, respectively. The Statistical Package for the Social Sciences version 26.0 by IBM Corp in Armonk, NY, was used to calculate frequencies, percentages and create statistical diagrams. Results: In the year 2022, the overall success rate of IUI was 5.3%. A majority of infertile men, representing 78.9%, fell within the age range of 30–39 years, and oligozoospermia emerged as the most common semen abnormality, affecting 45.6% of the infertile men in this study. Conclusion: Our study revealed that the IUI success rate in the country was 5.3%. This success rate of IUI in the country was found to be low compared to the success rate in neighboring countries. This is important information for patients to make informed decisions, aids fertility specialists in devising treatment plans, directs the allocation of resources, drives research and development initiatives, and informs policy and strategic adjustments at the national level.