Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study

Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study Sholen Acharya, Sheila Balakrishnan, Reji Mohan, Deepak Rath This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6548788/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim Severe male factor infertility presents challenges in assisted reproductive technology (ART). This study evaluated whether severe male factor infertility impacts clinical pregnancy outcomes following IVF-ICSI compared to non-male factor cases. Methods In this retrospective cohort study at the Department of Reproductive Medicine and Surgery, SAT Hospital, Government Medical College, Thiruvananthapuram, couples undergoing IVF-ICSI between January 2017 and December 2020 were divided into severe male factor(Group 1) (n = 51); and non-male factor (Group 2) (n = 51) groups, matched for female age, BMI, and ovarian reserve. Outcomes compared included clinical pregnancy rates based on sperm source (ejaculated vs. surgically retrieved) and male factor type (severe oligoasthenoteratozoospermia vs. azoospermia). Statistical analysis utilized univariate and multivariate logistic regression. Results The overall clinical pregnancy rate (CPR) was 75.5%. Group 1 (severe male factor) achieved a CPR of 68.6%, while Group 2 (non-male factor) achieved 82.4%, a difference that was not statistically significant (p = 0.107). Within Group 1, no significant differences were found between outcomes using ejaculated versus surgically retrieved sperm (p = 0.393). Logistic regression showed lower odds of pregnancy with severe male factor infertility [OR 0.469, 95% CI: 0.185–1.190], but this was not statistically significant (p = 0.111). Conclusion Severe male factor infertility, including cases requiring surgical sperm retrieval, does not significantly compromise clinical pregnancy rates in IVF-ICSI cycles when female factors and treatment protocols are optimized. Obstetrics & Gynecology Severe male infertility IVF-ICSI azoospermia oligoasthenoteratozoospermia surgical sperm retrieval clinical pregnancy rate Figures Figure 1 Introduction Infertility affects approximately 10–15% of couples globally, with male factors contributing to nearly half of these cases either alone or in combination with female factors 1 . Severe male factor infertility, encompassing conditions such as severe oligoasthenoteratozoospermia (OAT) and azoospermia, presents unique challenges in assisted reproductive technology (ART) programs. The advent of intracytoplasmic sperm injection (ICSI) has revolutionized the management of severe male infertility by enabling successful fertilization with minimal viable spermatozoa 2 . However, questions persist regarding the impact of compromised sperm quality on embryo development, implantation, and clinical pregnancy rates, particularly when compared to IVF-ICSI outcomes in couples without male factor infertility. Some studies suggest that despite poor semen parameters, ICSI can largely overcome male infertility, resulting in clinical pregnancy and live birth rates comparable to those of non-male factor infertility cases 3 . Conversely, concerns have been raised that sperm from severely affected males may harbor higher rates of DNA fragmentation or epigenetic alterations, potentially influencing reproductive outcomes 4 . This retrospective cohort study aims to assess whether severe male factor infertility affects clinical pregnancy outcomes following IVF-ICSI in a matched cohort at a tertiary care center. By comparing couples affected by severe male factor infertility to those without, and further evaluating outcomes based on the sperm source (ejaculated vs. surgically retrieved), this study aims to offer clinically relevant insights into how the severity of male infertility influences outcomes in contemporary assisted reproductive technology (ART) practice. Methods Study Design and Setting This retrospective cohort study was conducted at the Department of Reproductive Medicine and Surgery, Sri Avittom Thirunal (SAT) Hospital, Government Medical College, Thiruvananthapuram, Kerala. Ethical clearance was obtained from the Institutional Ethics Committee before initiating the study. Patient records from January 1, 2017, to December 31, 2020, were reviewed to identify eligible couples who had undergone IVF with ICSI. Participant Selection The study included couples undergoing IVF-ICSI treatment and was categorized into two cohorts: Group 1 (Severe Male Factor Group): Couples with severe male factor infertility who underwent IVF-ICSI using autologous sperm, either ejaculated or surgically retrieved. Group 2 (Non-Male Factor Group): Couples with no male factor infertility, including a small subset with azoospermia managed via donor sperm. To reduce bias, female partners in both groups were matched for age, BMI, and ovarian reserve markers (AMH, AFC)—factors known to influence IVF outcomes 5 . Couples were excluded if the female partner had diminished ovarian reserve, or confounding uterine or endometrial pathologies, such as endometriosis, adenomyosis, fibroids, or hydrosalpinx. Due to limited donor sperm IVF-ICSI cycles at our centre the control group (group 2) primarily comprised women with infertility related to PCOS, tubal block, or unexplained causes, where oocyte quality and endometrial receptivity were not severely compromised. A sample size calculation, based on a presumed 60% clinical pregnancy rate in PCOS patients undergoing IVF 6 and an expected 50% reduction due to male factor infertility 7 , indicated that 40 couples per group would achieve 95% confidence and 80% power. We recruited 51 couples in each group. Data Collection Baseline demographic and clinical data were extracted from patient records into Microsoft Excel. All couples had undergone a comprehensive infertility workup including hormonal evaluation (FSH, LH, TSH, PRL), ovarian reserve assessment (AMH, antral follicle count), transvaginal ultrasound for female partners, and semen analysis for male partners. Semen analysis followed WHO guidelines and was performed after 2–3 days of abstinence using ejaculated samples obtained via masturbation. Severe male factor infertility was defined as: Severe oligoasthenoteratozoospermia (OAT): sperm concentration < 16 million/mL, progressive motility < 30%, normal morphology < 4% 8 Azoospermia: complete absence of sperm in the ejaculate The source of sperm—ejaculate, surgically retrieved, or donor—was documented, along with IVF outcomes including embryo development and clinical pregnancy, defined as visualization of an intrauterine gestational sac on ultrasound. IVF-ICSI and Embryo Transfer Procedures Procedures were performed according to standardized institutional protocols, as previously published 9 . Key steps included: Ovarian Stimulation & Oocyte Retrieval Controlled ovarian stimulation using GnRH antagonist or long agonist protocols, with HMG (MENOPUR) or recombinant FSH (GONAL-F), was tailored to individual ovarian reserve. Final oocyte maturation was triggered using hCG, GnRH agonist, or dual trigger, followed by ultrasound-guided oocyte retrieval 35 hours later. Sperm Collection and Preparation Ejaculated sperm Processed using a two-layer (40%/80%) discontinuous density gradient centrifugation. Surgically retrieved sperm: PESA (Percutaneous Epididymal Sperm Aspiration): Performed under local anesthesia using a 23G needle to aspirate epididymal fluid. TESA (Testicular Sperm Aspiration): Performed with an 18G needle to aspirate testicular tissue for sperm extraction. Intra-cytoplasmic sperm injection (ICSI), fertilization & Embryo Culture Intracytoplasmic sperm injection (ICSI) was performed on all mature oocytes (metaphase II), using a micromanipulator under an inverted microscope. A single, motile, morphologically normal sperm was immobilized and injected into the oocyte cytoplasm. Fertilization was assessed 16 hours post-ICSI. Embryos were cultured in G-TL medium and graded based on the Istanbul consensus. Cryopreservation and Embryo Transfer Embryos were vitrified using the Kitazato Cryotop method as per the center’s “all-freeze” policy. In frozen embryo transfer (FET) cycles, endometrial preparation involved estradiol valerate and progesterone, with or without GnRH agonist downregulation. Embryos were warmed, cultured, and graded for transfer using Istanbul criteria (cleavage/morula ) or Gardner and Schoolcraft system (blastocysts). Transfer was performed under transabdominal ultrasound guidance using a Sydney IVF catheter. Luteal Support and Pregnancy Confirmation Post-transfer, luteal support was provided with vaginal progesterone gel. Serum β-hCG was measured 12 days after embryo transfer. Clinical pregnancy was confirmed by ultrasound at 6 weeks. Outcome Measures The primary outcome was clinical pregnancy, defined as the presence of an intrauterine gestational sac, with or without a fetal pole. Pregnancy rates were compared between groups (male factor vs. non-male factor infertility), with further subgroup analyses by type of male factor (severe OAT vs. azoospermia), sperm source (ejaculate, surgically retrieved, donor). Statistical Analysis Statistical analysis were performed using Jamovi software 10 . Continuous variables were tested for normality using Shapiro-Wilk test and expressed as mean ± standard deviation (SD) and median. Categorical variables were analyzed using Chi-square test and continuous variables using Student’s t-test (normal distribution) or Mann–Whitney U test (non-normal distribution). A univariate logistic regression model was used to examine the association between male factor infertility (using autologous sperm) and clinical pregnancy outcome. A multivariate logistic regression model was constructed to control for potential confounders including female age, BMI, AMH, and AFC, and to identify independent predictors of IVF-ICSI success. A two-tailed p-value < 0.05 was considered statistically significant. Ethical considerations This study was conducted in accordance with the ethical standards of the Institutional Ethics Committee of Government Medical College, Thiruvananthapuram, and with the 1964 Helsinki declaration and its later amendments. Ethical approval was obtained prior to the initiation of the study. As this was a retrospective analysis of anonymized patient data, the requirement for individual informed consent was waived by the Institutional Ethics Committee. Results Clinical characteristics of study participants (Table 1) In Group 1 (n= 51), male factor infertility was present in all cases, with 66.7% (n = 34) diagnosed with severe oligoasthenoteratozoospermia (OAT) and 33.3% (n = 17) with azoospermia . Female factor (PCOS) was present in 21.6% of couples. The source of sperm was ejaculate in 64.7% and surgically retrieved in 35.3%. Table 1 Distribution of male, female factor and source of sperm between two study groups In Group 2 (n= 51), there was no male factor as those with azoospermia (n= 3, 5.9%) were managed with donor sperms. The causes of infertility included female factor like PCOS (43.1%, n = 22), tubal block (15.7%, n = 8), and unexplained infertility (35.3%, n = 18). There was significant difference between group 1 and group 2 in terms of male and female factor as well as sperm source. Baseline female partner characteristics (Table 2) Female age, BMI, AMH, and AFC—were comparable between the two groups. similar between groups. Age and BMI were normally distributed and analyzed using student’s t -tests, while AMH and AFC were non-normally distributed and compared using the Mann-Whitney U test. Table 2 Distribution of female age, BMI and ovarian reserve markers between two study groups Outcome measures (Table 3) The overall clinical pregnancy rate (CPR) across both groups was 75.5% (77 out of 102 couples). In Group 1, which consisted of couples with severe male factor infertility, the clinical pregnancy rate was 68.6% (35/51), while in Group 2, which included couples without male factor infertility (including those using donor sperm), the pregnancy rate was 82.4% (42/51); however, this difference did not reach statistical significance (p = 0.107). On comparing outcome between ejaculated sperms with male factor vs ejaculated sperms without male factor, there was no significant difference in the clinical pregnancy rates (p-value 0.365). Similarly, among couples using surgically retrieved sperm in Group 1, the pregnancy rate was 64.7% (11/18), which again was not significantly different when compared to the 100% pregnancy rate observed in the small number of donor sperm users in Group 2 (3/3 couples, p = 0.219). Table 3 Clinical pregnancy distribution between study groupWithin the male factor group (Group 1), couples with severe oligoasthenoteratozoospermia (OAT) had a CPR of 70.6% (24/34), while those with azoospermia had a slightly lower CPR of 64.7% (11/17), with no significant difference (p = 0.670), indicating similar treatment success regardless of severity of male factor condition. When comparing sperm source within Group 1, those using ejaculated sperm had a higher clinical pregnancy rate (72.7%, 24/33) compared to those using surgically retrieved sperm (61.1%, 11/18), although this difference too was not statistically significant (p = 0.393), suggesting that both methods of sperm acquisition can yield comparable pregnancy outcomes in the context of IVF-ICSI. Regression analysis Logistic regression analysis was performed using both the groups to evaluate whether the presence of severe male factor infertility impacted IVF-ICSI outcomes. The univariate model (Table 4) showed that male factor infertility was associated with lower odds of achieving pregnancy [OR 0.469 (95% CI: 0.185 to 1.190)] but this was not statistically significant ( p = 0.111). The model explained only a small proportion of variance in outcomes (McFadden’s R² = 0.0231). The ROC analysis of this model (Figure 1) demonstrated perfect sensitivity (1.00), identifying all pregnancies correctly, but failed to distinguish non-pregnancies (specificity = 0.00), with an area under the curve (AUC) of just 0.593, reflecting poor discriminative ability. Table 4 Univariate logistic regression model assessing the impact of severe male factor infertility (Group 1 vs. Group 2) on clinical pregnancy outcomes following IVF-ICSI. To adjust for potential confounders, a multivariate logistic regression analysis (Table 5) was conducted, including age, BMI, AMH, and AFC as covariates. Male factor infertility remained a non-significant predictor of pregnancy (adjusted odds ratio = 0.440, 95% CI: 0.159 to 1.22, p = 0.115), and none of the additional covariates significantly impacted the likelihood of pregnancy either (all p-values > 0.05), reinforcing the notion that neither male factor status nor baseline female characteristics were strong independent predictors of clinical pregnancy in this cohort undergoing IVF-ICSI. Table 5 Multivariate logistic regression model evaluating the association between severe male factor infertility and clinical pregnancy following IVF-ICSI, adjusting for female partner characteristics (age, BMI, AMH, and AFC). Discussion This study aimed to evaluate the impact of severe male factor infertility on IVF-ICSI outcomes by comparing clinical pregnancy rates between couples with severe male factor infertility (Group 1) and those without (Group 2), with further stratification based on the type of male factor and source of sperm used. Despite numerical differences in pregnancy rates between groups, our findings suggest that severe male factor infertility, including cases requiring surgical sperm retrieval, does not significantly compromise clinical pregnancy outcomes in IVF-ICSI cycles when appropriate techniques and laboratory standards are employed. Group 1 consisting of couples with either severe oligoasthenoteratozoospermia (OAT) or azoospermia using autologous sperm, achieved a clinical pregnancy rate of 68.6%, while Group 2, comprising couples without male factor infertility (including those who used donor sperm), showed a higher, though statistically non-significant, pregnancy rate of 82.4% (p = 0.107). This finding reinforces the current understanding that ICSI is a highly effective technique for overcoming poor semen parameters, allowing fertilization and pregnancy rates to approach those seen in non-male factor cases. Those with prior fertilization failures have seen improved outcome due to the technique of aggressive sperm immobilization used in ICSI 11 . When comparing outcomes based on sperm source, couples using ejaculated sperm in the presence of male factor infertility achieved a clinical pregnancy rate of 72.7%, which was not significantly different from the 81.3% seen in those using ejaculated sperm without male factor (p = 0.365). ICSI has shown higher success rates in male infertility but not improve outcomes in those without male factor compared to conventional IVF, indicating its specific advantage in male infertility 12 . The clinical pregnancy rate among couples using surgically retrieved sperm was 64.7%, which also did not differ significantly from the 100% success rate observed in a small number of donor sperm cycles (p = 0.219). Although the use of donor sperm yielded excellent results, the limited number of cases (n = 3) precludes definitive conclusions. Other studies have consistently showed that use of donor sperms have higher IVF success rates compared to partner sperm in severe male infertility 13 , 14 . Due to limited donor IVF cycles at our centre we were unable to draw conclusive results. But our study shows that using partner sperm in severe male infertility with ICSI gives a viable option and has comparable results to those without male factor. Within the severe male factor group, clinical pregnancy rates did not differ significantly between those with severe OAT (70.6%) and those with azoospermia (64.7%) (p = 0.670). Moreover, when comparing sperm acquisition methods within this group, ejaculated sperm yielded a higher pregnancy rate (72.7%) compared to surgically retrieved sperm (61.1%), though the difference was not statistically significant (p = 0.393). These observations are clinically important, as they support the use of surgical sperm retrieval in azoospermic men without expecting a substantial compromise in treatment outcomes. The success of ICSI is highly dependent on the selection of viable sperm, and techniques like using testicular spermatozoa or aggressive sperm immobilization can further enhance outcomes 11 , 15 . Regression analyses further substantiated these observations. The univariate logistic model indicated a trend toward lower odds of pregnancy in cases with severe male factor infertility (OR = 0.469), though the association was not statistically significant (p = 0.111). The multivariate analysis, which controlled for female age, BMI, AMH, and AFC, also failed to identify male factor status or any female partner variables as independent predictors of clinical pregnancy, reinforcing the conclusion that with good female parameters and standardised treatment protocols, male factor infertility does not independently reduce the likelihood of conception. The rigorous inclusion criteria of this study, excluding couples with diminished ovarian reserve or endometrial factors, allowed for a focused examination of the male factor’s impact, minimizing confounding influences. Furthermore, standardized stimulation, ICSI, culture, and transfer protocols reduced procedural variability, enhancing the internal validity of the findings. Limitations of the study include its retrospective design and single-center setting, which may limit generalizability. The relatively small sample size, particularly in the donor sperm subgroup, also limits the power to detect small but potentially meaningful differences in outcomes. Future prospective, multicentric studies with larger cohorts are warranted to validate these findings and assess live birth rates, cumulative pregnancy outcomes, and offspring health across different sperm sources and male infertility etiologies. Conclusion This study demonstrates that the presence of severe male factor infertility, including azoospermia requiring surgical sperm retrieval, does not significantly impact clinical pregnancy outcomes in IVF-ICSI cycles when female partner characteristics are comparable and standard ART protocols are followed. These results provide reassurance for couples with severe male factor infertility and support the continued use of ICSI with autologous sperm—whether ejaculated or surgically retrieved—as an effective treatment option. Declarations Disclosure The authors declare that there is no conflict of Interest. Acknowledgements None Data Availability Statement The datasets generated and/or analysed during the current study are available in the Mendeley data repository 16 . References Agarwal A, Mulgund A, Hamada A, Chyatte MR (2015) A unique view on male infertility around the globe. Reprod Biol Endocrinol 13(1):37. 10.1186/s12958-015-0032-1 Palermo G (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340(8810):17–18. 10.1016/0140-6736(92)92425-F Esteves SC, Roque M, Bedoschi G, Haahr T, Humaidan P (2018) Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol 15(9):535–562. 10.1038/s41585-018-0051-8 Zini A, Sigman M (2009) Are Tests of Sperm DNA Damage Clinically Useful? Pros and Cons. J Androl 30(3):219–229. 10.2164/jandrol.108.006908 Shingshetty L, Cameron NJ, Mclernon DJ, Bhattacharya S (2024) Predictors of success after in vitro fertilization. Fertil Steril 121(5):742–751. 10.1016/j.fertnstert.2024.03.003 Nguyen TH, Nguyen TTD, Le HT, Vo TKQ, Le TTA (2024) Research on clinical pregnancy rate and some factors related to IVF outcomes in women with polycystic ovary syndrome at Can Tho Obstetrics and Gynecology Hospital. TC Phụ sản 22(2):59–67. 10.46755/vjog.2024.2.1687 Riffenburgh RH, Gillen DL (2020) Sample size estimation. Statistics in Medicine. Elsevier, pp 533–563. doi: 10.1016/B978-0-12-815328-4.00021-8 Campbell M Fertile man semen parameters 2020 – an update to the data collated for the WHO semen analysis manual 2010. Published online 2021:223 KB. 10.15132/10000163 Acharya S, Balakrishnan S, Rath D (2025) Pregnancy Rates After Frozen Embryo Transfer: Insights from an Indian Government Hospital. IJMRGE 6(2):965–972. 10.54660/.IJMRGE.2025.6.2.965-972 The jamovi project (2024) jamovi. (Version 2.6) [Computer Software]. https://www.jamovi.org Chou CW, Chen SU, Chang CH, Tsai YY, Huang CC (2024) Aggressive sperm immobilization improves reproductive outcomes in patients with suboptimal semen parameters and previous ICSI fertilization failure. Sci Rep 14(1):5363. 10.1038/s41598-024-56092-4 Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ (2015) Trends in Use of and Reproductive Outcomes Associated With Intracytoplasmic Sperm Injection. JAMA 313(3):255. 10.1001/jama.2014.17985 Mignini Renzini M, Dal Canto M, Guglielmo MC et al (2021) Sperm donation: an alternative to improve post-ICSI live birth rates in advanced maternal age patients. Hum Reprod 36(8):2148–2156. 10.1093/humrep/deab148 Cai H, Gordts S, Sun J, Meng B, Shi J (2020) Reproductive outcomes with donor sperm in couples with severe male-factor infertility after intracytoplasmic sperm injection failures. J Assist Reprod Genet 37(8):1883–1893. 10.1007/s10815-020-01828-0 Chen T, Fan D, Wang X et al (2022) ICSI outcomes for infertile men with severe or complete asthenozoospermia. Basic Clin Androl 32(1):6. 10.1186/s12610-022-00155-x Acharya S Dataset for Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study. Published online 2025. 10.17632/8zjds5bf8y.1 Tables Table 1 to 5 are available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. Supplementary Files Table15.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6548788","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449176692,"identity":"8ce0baab-6949-4f20-9d3c-d58e41453672","order_by":0,"name":"Sholen Acharya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYDACCQbGAyDaAMyrAGJm5gZCWhiQtJwBaWEkRQtjG5jEr0V+dvOBAx932Mmbs599JvFzXm00fztQy4+KbTi1GNw5lnBw5plkw5096WaSvduO5844zNjA2HPmNm4tEjkGh3nbmBMMDqSxSfBuO5bbANTCzNiGW4v8DKCWv231CQbnn7FJ/p1zLHc+IS0MN4BaGNsOJxjcSGOT5m2oyd1ASAtQZcLB3rbjhhtuPGO2ljl2IHcjUMtBfH6Rn5F88MHPtmp5g/NpjDff1NTlzjt/+OCDHxV4HIYEWIBxdBjMOkCUeiBg/sDAUEes4lEwCkbBKBhBAADK8GEl1mKpgwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0009-4073-6315","institution":"Department of Reproductive Medicine and Surgery, Government Medical College, Thiruvananthapuram, Kerala, India","correspondingAuthor":true,"prefix":"","firstName":"Sholen","middleName":"","lastName":"Acharya","suffix":""},{"id":449176693,"identity":"e59e5c30-092d-47ec-aec1-c1f9cf96d94e","order_by":1,"name":"Sheila Balakrishnan","email":"","orcid":"","institution":"Department of Reproductive Medicine and Surgery, Government Medical College, Thiruvananthapuram, Kerala, India","correspondingAuthor":false,"prefix":"","firstName":"Sheila","middleName":"","lastName":"Balakrishnan","suffix":""},{"id":449176694,"identity":"0b54a222-bbdd-420e-a43f-88a63bd92ebc","order_by":2,"name":"Reji Mohan","email":"","orcid":"","institution":"Department of Reproductive Medicine and Surgery, Government Medical College, Thiruvananthapuram, Kerala, India","correspondingAuthor":false,"prefix":"","firstName":"Reji","middleName":"","lastName":"Mohan","suffix":""},{"id":449176695,"identity":"992f1519-cd9c-4ebf-a32d-dba636bd87f4","order_by":3,"name":"Deepak Rath","email":"","orcid":"","institution":"Department of Internal Medicine, John H Stroger Jr. Hospital of Cook County, Chicago, USA","correspondingAuthor":false,"prefix":"","firstName":"Deepak","middleName":"","lastName":"Rath","suffix":""}],"badges":[],"createdAt":"2025-04-28 14:24:12","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6548788/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6548788/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81956306,"identity":"f75715ce-f115-4585-b5ca-72da67c921bc","added_by":"auto","created_at":"2025-05-05 09:55:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":245223,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver Operating Characteristic (ROC) curve illustrating the predictive performance of severe male factor infertility status on pregnancy outcome in IVF-ICSI cycles. Area under curve(AUC) = 0.593\u003c/p\u003e","description":"","filename":"Screenshot20250428at9.42.06AM.png","url":"https://assets-eu.researchsquare.com/files/rs-6548788/v1/e7f074071f8194d222a7a01c.png"},{"id":81958205,"identity":"46804c8d-acc9-45c7-94f7-49c03d95959c","added_by":"auto","created_at":"2025-05-05 10:11:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":814695,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6548788/v1/abc31b5a-3d19-4303-bd0c-098cc845a66e.pdf"},{"id":81956304,"identity":"c840fa46-8858-4270-9013-c3b51b5da277","added_by":"auto","created_at":"2025-05-05 09:55:19","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":26946,"visible":true,"origin":"","legend":"","description":"","filename":"Table15.docx","url":"https://assets-eu.researchsquare.com/files/rs-6548788/v1/c2d8f3bd0d6af44534e6d570.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eImpact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInfertility affects approximately 10\u0026ndash;15% of couples globally, with male factors contributing to nearly half of these cases either alone or in combination with female factors \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Severe male factor infertility, encompassing conditions such as severe oligoasthenoteratozoospermia (OAT) and azoospermia, presents unique challenges in assisted reproductive technology (ART) programs. The advent of intracytoplasmic sperm injection (ICSI) has revolutionized the management of severe male infertility by enabling successful fertilization with minimal viable spermatozoa \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, questions persist regarding the impact of compromised sperm quality on embryo development, implantation, and clinical pregnancy rates, particularly when compared to IVF-ICSI outcomes in couples without male factor infertility.\u003c/p\u003e \u003cp\u003eSome studies suggest that despite poor semen parameters, ICSI can largely overcome male infertility, resulting in clinical pregnancy and live birth rates comparable to those of non-male factor infertility cases \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Conversely, concerns have been raised that sperm from severely affected males may harbor higher rates of DNA fragmentation or epigenetic alterations, potentially influencing reproductive outcomes \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis retrospective cohort study aims to assess whether severe male factor infertility affects clinical pregnancy outcomes following IVF-ICSI in a matched cohort at a tertiary care center. By comparing couples affected by severe male factor infertility to those without, and further evaluating outcomes based on the sperm source (ejaculated vs. surgically retrieved), this study aims to offer clinically relevant insights into how the severity of male infertility influences outcomes in contemporary assisted reproductive technology (ART) practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was conducted at the Department of Reproductive Medicine and Surgery, Sri Avittom Thirunal (SAT) Hospital, Government Medical College, Thiruvananthapuram, Kerala. Ethical clearance was obtained from the Institutional Ethics Committee before initiating the study. Patient records from January 1, 2017, to December 31, 2020, were reviewed to identify eligible couples who had undergone IVF with ICSI.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipant Selection\u003c/h3\u003e\n\u003cp\u003eThe study included couples undergoing IVF-ICSI treatment and was categorized into two cohorts:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eGroup 1 (Severe Male Factor Group): Couples with severe male factor infertility who underwent IVF-ICSI using autologous sperm, either ejaculated or surgically retrieved.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eGroup 2 (Non-Male Factor Group): Couples with no male factor infertility, including a small subset with azoospermia managed via donor sperm.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eTo reduce bias, female partners in both groups were matched for age, BMI, and ovarian reserve markers (AMH, AFC)\u0026mdash;factors known to influence IVF outcomes \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Couples were excluded if the female partner had diminished ovarian reserve, or confounding uterine or endometrial pathologies, such as endometriosis, adenomyosis, fibroids, or hydrosalpinx.\u003c/p\u003e \u003cp\u003eDue to limited donor sperm IVF-ICSI cycles at our centre the control group (group 2) primarily comprised women with infertility related to PCOS, tubal block, or unexplained causes, where oocyte quality and endometrial receptivity were not severely compromised. A sample size calculation, based on a presumed 60% clinical pregnancy rate in PCOS patients undergoing IVF \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e and an expected 50% reduction due to male factor infertility \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, indicated that 40 couples per group would achieve 95% confidence and 80% power. We recruited 51 couples in each group.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eBaseline demographic and clinical data were extracted from patient records into Microsoft Excel. All couples had undergone a comprehensive infertility workup including hormonal evaluation (FSH, LH, TSH, PRL), ovarian reserve assessment (AMH, antral follicle count), transvaginal ultrasound for female partners, and semen analysis for male partners. Semen analysis followed WHO guidelines and was performed after 2\u0026ndash;3 days of abstinence using ejaculated samples obtained via masturbation.\u003c/p\u003e \u003cp\u003eSevere male factor infertility was defined as:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSevere oligoasthenoteratozoospermia (OAT): sperm concentration\u0026thinsp;\u0026lt;\u0026thinsp;16\u0026nbsp;million/mL, progressive motility\u0026thinsp;\u0026lt;\u0026thinsp;30%, normal morphology\u0026thinsp;\u0026lt;\u0026thinsp;4% \u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAzoospermia: complete absence of sperm in the ejaculate\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe source of sperm\u0026mdash;ejaculate, surgically retrieved, or donor\u0026mdash;was documented, along with IVF outcomes including embryo development and clinical pregnancy, defined as visualization of an intrauterine gestational sac on ultrasound.\u003c/p\u003e\n\u003ch3\u003eIVF-ICSI and Embryo Transfer Procedures\u003c/h3\u003e\n\u003cp\u003eProcedures were performed according to standardized institutional protocols, as previously published \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Key steps included:\u003c/p\u003e\n\u003ch3\u003eOvarian Stimulation \u0026 Oocyte Retrieval\u003c/h3\u003e\n\u003cp\u003eControlled ovarian stimulation using GnRH antagonist or long agonist protocols, with HMG (MENOPUR) or recombinant FSH (GONAL-F), was tailored to individual ovarian reserve. Final oocyte maturation was triggered using hCG, GnRH agonist, or dual trigger, followed by ultrasound-guided oocyte retrieval 35 hours later.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSperm Collection and Preparation\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eEjaculated sperm\u003c/strong\u003e \u003cp\u003eProcessed using a two-layer (40%/80%) discontinuous density gradient centrifugation.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgically retrieved sperm:\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePESA (Percutaneous Epididymal Sperm Aspiration): Performed under local anesthesia using a 23G needle to aspirate epididymal fluid.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTESA (Testicular Sperm Aspiration): Performed with an 18G needle to aspirate testicular tissue for sperm extraction.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eIntra-cytoplasmic sperm injection (ICSI), fertilization \u0026 Embryo Culture\u003c/h3\u003e\n\u003cp\u003eIntracytoplasmic sperm injection (ICSI) was performed on all mature oocytes (metaphase II), using a micromanipulator under an inverted microscope. A single, motile, morphologically normal sperm was immobilized and injected into the oocyte cytoplasm. Fertilization was assessed 16 hours post-ICSI. Embryos were cultured in G-TL medium and graded based on the Istanbul consensus.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCryopreservation and Embryo Transfer\u003c/h2\u003e \u003cp\u003eEmbryos were vitrified using the Kitazato Cryotop method as per the center\u0026rsquo;s \u0026ldquo;all-freeze\u0026rdquo; policy. In frozen embryo transfer (FET) cycles, endometrial preparation involved estradiol valerate and progesterone, with or without GnRH agonist downregulation. Embryos were warmed, cultured, and graded for transfer using Istanbul criteria (cleavage/morula\u003cb\u003e)\u003c/b\u003e or Gardner and Schoolcraft system (blastocysts). Transfer was performed under transabdominal ultrasound guidance using a Sydney IVF catheter.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLuteal Support and Pregnancy Confirmation\u003c/h2\u003e \u003cp\u003ePost-transfer, luteal support was provided with vaginal progesterone gel. Serum β-hCG was measured 12 days after embryo transfer. Clinical pregnancy was confirmed by ultrasound at 6 weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cp\u003eThe primary outcome was clinical pregnancy, defined as the presence of an intrauterine gestational sac, with or without a fetal pole. Pregnancy rates were compared between groups (male factor vs. non-male factor infertility), with further subgroup analyses by type of male factor (severe OAT vs. azoospermia), sperm source (ejaculate, surgically retrieved, donor).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis were performed using Jamovi software \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Continuous variables were tested for normality using Shapiro-Wilk test and expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and median. Categorical variables were analyzed using Chi-square test and continuous variables using Student\u0026rsquo;s t-test (normal distribution) or Mann\u0026ndash;Whitney U test (non-normal distribution). A univariate logistic regression model was used to examine the association between male factor infertility (using autologous sperm) and clinical pregnancy outcome. A multivariate logistic regression model was constructed to control for potential confounders including female age, BMI, AMH, and AFC, and to identify independent predictors of IVF-ICSI success. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eEthical considerations\u003c/h2\u003e \u003cp\u003e This study was conducted in accordance with the ethical standards of the Institutional Ethics Committee of Government Medical College, Thiruvananthapuram, and with the 1964 Helsinki declaration and its later amendments. Ethical approval was obtained prior to the initiation of the study. As this was a retrospective analysis of anonymized patient data, the requirement for individual informed consent was waived by the Institutional Ethics Committee.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical characteristics of study participants (Table 1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn Group 1 (n= 51), male factor infertility was present in all cases,\u0026nbsp;with \u003cstrong\u003e66.7% (n = 34)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ediagnosed with\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003esevere oligoasthenoteratozoospermia (OAT)\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003e33.3% (n = 17)\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003ewith \u003cstrong\u003eazoospermia\u003c/strong\u003e. Female factor (PCOS) was present in 21.6% of couples. The source of sperm was ejaculate in 64.7% and surgically retrieved in 35.3%.\u003c/p\u003e\n\u003cp\u003eTable 1 Distribution of male, female factor and source of sperm between two study groups\u003c/p\u003e\n\u003cp\u003eIn Group 2 (n= 51), there was no male factor as those with azoospermia (n= 3, 5.9%) were managed with donor sperms. The causes of infertility included female factor like PCOS (43.1%, n = 22), tubal block (15.7%, n = 8), and unexplained infertility (35.3%, n = 18). There was significant difference between group 1 and group 2 in terms of male and female factor as well as sperm source.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline female partner characteristics (Table 2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFemale age, BMI, AMH, and AFC\u0026mdash;were comparable between the two groups. similar between groups. Age and BMI were normally distributed and analyzed using student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-tests, while AMH and AFC were non-normally distributed and compared using the Mann-Whitney U test.\u003c/p\u003e\n\u003cp\u003eTable 2 Distribution of female age, BMI and ovarian reserve markers between two study groups\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures (Table 3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe overall clinical pregnancy rate (CPR) across both groups was 75.5% (77 out of 102 couples). In Group 1, which consisted of couples with severe male factor infertility, the clinical pregnancy rate was 68.6% (35/51), while in Group 2, which included couples without male factor infertility (including those using donor sperm), the pregnancy rate was 82.4% (42/51); however, this difference did not reach statistical significance (p = 0.107). On comparing outcome between ejaculated sperms with male factor vs ejaculated sperms without male factor, there was no significant difference in the clinical pregnancy rates (p-value 0.365).\u0026nbsp;Similarly, among couples using surgically retrieved sperm in Group 1, the pregnancy rate was 64.7% (11/18), which again was not significantly different when compared to the 100% pregnancy rate observed in the small number of donor sperm users in Group 2 (3/3 couples, p = 0.219).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Clinical pregnancy distribution between study groupWithin the male factor group (Group 1), couples with severe oligoasthenoteratozoospermia (OAT) had a CPR of 70.6% (24/34), while those with azoospermia had a slightly lower CPR of 64.7% (11/17), with no significant difference (p = 0.670), indicating similar treatment success regardless of severity of male factor condition.\u0026nbsp;When comparing sperm source within Group 1, those using ejaculated sperm had a higher clinical pregnancy rate (72.7%, 24/33) compared to those using surgically retrieved sperm (61.1%, 11/18), although this difference too was not statistically significant (p = 0.393), suggesting that both methods of sperm acquisition can yield comparable pregnancy outcomes in the context of IVF-ICSI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLogistic regression analysis was performed using both the groups to evaluate whether the presence of severe male factor infertility impacted IVF-ICSI outcomes. The univariate model (Table 4) showed that male factor infertility was associated with lower odds of achieving pregnancy [OR 0.469 (95% CI: 0.185 to 1.190)] but this was not statistically significant (\u003cem\u003ep\u003c/em\u003e = 0.111). The model explained only a small proportion of variance in outcomes (McFadden\u0026rsquo;s R\u0026sup2; = 0.0231). The ROC analysis of this model (Figure 1) demonstrated perfect sensitivity (1.00), identifying all pregnancies correctly, but failed to distinguish non-pregnancies (specificity = 0.00), with an area under the curve (AUC) of just 0.593, reflecting poor discriminative ability.\u003c/p\u003e\n\u003cp\u003eTable 4 Univariate logistic regression model assessing the impact of severe male factor infertility (Group 1 vs. Group 2) on clinical pregnancy outcomes following IVF-ICSI.\u003c/p\u003e\n\u003cp\u003eTo adjust for potential confounders, a multivariate logistic regression analysis (Table 5) was conducted, including age, BMI, AMH, and AFC as covariates.\u0026nbsp;Male factor infertility remained a non-significant predictor of pregnancy (adjusted odds ratio = 0.440, 95% CI: 0.159 to 1.22, p = 0.115), and none of the additional covariates significantly impacted the likelihood of pregnancy either (all p-values \u0026gt; 0.05), reinforcing the notion that neither male factor status nor baseline female characteristics were strong independent predictors of clinical pregnancy in this cohort undergoing IVF-ICSI.\u003c/p\u003e\n\u003cp\u003eTable 5 Multivariate logistic regression model evaluating the association between severe male factor infertility and clinical pregnancy following IVF-ICSI, adjusting for female partner characteristics (age, BMI, AMH, and AFC).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to evaluate the impact of severe male factor infertility on IVF-ICSI outcomes by comparing clinical pregnancy rates between couples with severe male factor infertility (Group 1) and those without (Group 2), with further stratification based on the type of male factor and source of sperm used. Despite numerical differences in pregnancy rates between groups, our findings suggest that severe male factor infertility, including cases requiring surgical sperm retrieval, does not significantly compromise clinical pregnancy outcomes in IVF-ICSI cycles when appropriate techniques and laboratory standards are employed.\u003c/p\u003e \u003cp\u003eGroup 1 consisting of couples with either severe oligoasthenoteratozoospermia (OAT) or azoospermia using autologous sperm, achieved a clinical pregnancy rate of 68.6%, while Group 2, comprising couples without male factor infertility (including those who used donor sperm), showed a higher, though statistically non-significant, pregnancy rate of 82.4% (p\u0026thinsp;=\u0026thinsp;0.107). This finding reinforces the current understanding that ICSI is a highly effective technique for overcoming poor semen parameters, allowing fertilization and pregnancy rates to approach those seen in non-male factor cases. Those with prior fertilization failures have seen improved outcome due to the technique of aggressive sperm immobilization used in ICSI \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhen comparing outcomes based on sperm source, couples using ejaculated sperm in the presence of male factor infertility achieved a clinical pregnancy rate of 72.7%, which was not significantly different from the 81.3% seen in those using ejaculated sperm without male factor (p\u0026thinsp;=\u0026thinsp;0.365). ICSI has shown higher success rates in male infertility but not improve outcomes in those without male factor compared to conventional IVF, indicating its specific advantage in male infertility \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The clinical pregnancy rate among couples using surgically retrieved sperm was 64.7%, which also did not differ significantly from the 100% success rate observed in a small number of donor sperm cycles (p\u0026thinsp;=\u0026thinsp;0.219). Although the use of donor sperm yielded excellent results, the limited number of cases (n\u0026thinsp;=\u0026thinsp;3) precludes definitive conclusions. Other studies have consistently showed that use of donor sperms have higher IVF success rates compared to partner sperm in severe male infertility \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Due to limited donor IVF cycles at our centre we were unable to draw conclusive results. But our study shows that using partner sperm in severe male infertility with ICSI gives a viable option and has comparable results to those without male factor.\u003c/p\u003e \u003cp\u003eWithin the severe male factor group, clinical pregnancy rates did not differ significantly between those with severe OAT (70.6%) and those with azoospermia (64.7%) (p\u0026thinsp;=\u0026thinsp;0.670). Moreover, when comparing sperm acquisition methods within this group, ejaculated sperm yielded a higher pregnancy rate (72.7%) compared to surgically retrieved sperm (61.1%), though the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.393). These observations are clinically important, as they support the use of surgical sperm retrieval in azoospermic men without expecting a substantial compromise in treatment outcomes. The success of ICSI is highly dependent on the selection of viable sperm, and techniques like using testicular spermatozoa or aggressive sperm immobilization can further enhance outcomes \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegression analyses further substantiated these observations. The univariate logistic model indicated a trend toward lower odds of pregnancy in cases with severe male factor infertility (OR\u0026thinsp;=\u0026thinsp;0.469), though the association was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.111). The multivariate analysis, which controlled for female age, BMI, AMH, and AFC, also failed to identify male factor status or any female partner variables as independent predictors of clinical pregnancy, reinforcing the conclusion that with good female parameters and standardised treatment protocols, male factor infertility does not independently reduce the likelihood of conception.\u003c/p\u003e \u003cp\u003eThe rigorous inclusion criteria of this study, excluding couples with diminished ovarian reserve or endometrial factors, allowed for a focused examination of the male factor\u0026rsquo;s impact, minimizing confounding influences. Furthermore, standardized stimulation, ICSI, culture, and transfer protocols reduced procedural variability, enhancing the internal validity of the findings.\u003c/p\u003e \u003cp\u003eLimitations of the study include its retrospective design and single-center setting, which may limit generalizability. The relatively small sample size, particularly in the donor sperm subgroup, also limits the power to detect small but potentially meaningful differences in outcomes. Future prospective, multicentric studies with larger cohorts are warranted to validate these findings and assess live birth rates, cumulative pregnancy outcomes, and offspring health across different sperm sources and male infertility etiologies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates that the presence of severe male factor infertility, including azoospermia requiring surgical sperm retrieval, does not significantly impact clinical pregnancy outcomes in IVF-ICSI cycles when female partner characteristics are comparable and standard ART protocols are followed. These results provide reassurance for couples with severe male factor infertility and support the continued use of ICSI with autologous sperm\u0026mdash;whether ejaculated or surgically retrieved\u0026mdash;as an effective treatment option.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eDisclosure\u003c/h2\u003e \u003cp\u003eThe authors declare that there is no conflict of Interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eData Availability Statement\u003c/h2\u003e \u003cp\u003eThe datasets generated and/or analysed during the current study are available in the Mendeley data repository \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAgarwal A, Mulgund A, Hamada A, Chyatte MR (2015) A unique view on male infertility around the globe. 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Basic Clin Androl 32(1):6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12610-022-00155-x\u003c/span\u003e\u003cspan address=\"10.1186/s12610-022-00155-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcharya S Dataset for Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study. Published online 2025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.17632/8zjds5bf8y.1\u003c/span\u003e\u003cspan address=\"10.17632/8zjds5bf8y.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Department of Reproductive Medicine and Surgery, Sri Avittom Thirunal (SAT) Hospital, Government Medical College, Thiruvananthapuram, Kerala, India","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Severe male infertility, IVF-ICSI, azoospermia, oligoasthenoteratozoospermia, surgical sperm retrieval, clinical pregnancy rate","lastPublishedDoi":"10.21203/rs.3.rs-6548788/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6548788/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eSevere male factor infertility presents challenges in assisted reproductive technology (ART). This study evaluated whether severe male factor infertility impacts clinical pregnancy outcomes following IVF-ICSI compared to non-male factor cases.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this retrospective cohort study at the Department of Reproductive Medicine and Surgery, SAT Hospital, Government Medical College, Thiruvananthapuram, couples undergoing IVF-ICSI between January 2017 and December 2020 were divided into severe male factor(Group 1) (n\u0026thinsp;=\u0026thinsp;51); and non-male factor (Group 2) (n\u0026thinsp;=\u0026thinsp;51) groups, matched for female age, BMI, and ovarian reserve. Outcomes compared included clinical pregnancy rates based on sperm source (ejaculated vs. surgically retrieved) and male factor type (severe oligoasthenoteratozoospermia vs. azoospermia). Statistical analysis utilized univariate and multivariate logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe overall clinical pregnancy rate (CPR) was 75.5%. Group 1 (severe male factor) achieved a CPR of 68.6%, while Group 2 (non-male factor) achieved 82.4%, a difference that was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.107). Within Group 1, no significant differences were found between outcomes using ejaculated versus surgically retrieved sperm (p\u0026thinsp;=\u0026thinsp;0.393). Logistic regression showed lower odds of pregnancy with severe male factor infertility [OR 0.469, 95% CI: 0.185\u0026ndash;1.190], but this was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.111).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSevere male factor infertility, including cases requiring surgical sperm retrieval, does not significantly compromise clinical pregnancy rates in IVF-ICSI cycles when female factors and treatment protocols are optimized.\u003c/p\u003e","manuscriptTitle":"Impact of Severe Male Factor Infertility on IVF-ICSI Outcomes: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-05 09:55:14","doi":"10.21203/rs.3.rs-6548788/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"25024a1a-ebc3-4dc6-bc71-149dd6c6ae35","owner":[],"postedDate":"May 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47798926,"name":"Obstetrics \u0026 Gynecology"}],"tags":[],"updatedAt":"2025-05-05T09:55:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-05 09:55:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6548788","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6548788","identity":"rs-6548788","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}