Optimizing outcomes in intrauterine insemination: A narrative synthesis of two decades of clinical research (2000-2024)

Sperm preparation plays a critical role in IUI by isolating highly motile, morphologically normal sperm and eliminating seminal plasma, debris, and immotile or apoptotic spermatozoa. Among the most commonly used methods are density gradient centrifugation (DGC) and the swim‐up (SU) technique. DGC is widely preferred for its ability to yield a high concentration of motile sperm while effectively removing reactive oxygen species‐generating cells, which compromise fertilization potential. 42 In a comparative study, superior sperm recovery and improved pregnancy outcomes with DGC, particularly in oligospermic samples, compared to the swim‐up method are reported 20 , 43 The SU technique, although less complex, remains effective in normozoospermic cases and offers a cost‐efficient alternative with acceptable clinical results. 44 In addition, emerging techniques such as hyaluronic acid binding and magnetic‐activated cell sorting have shown promise in enhancing sperm selection; however, their routine use in IUI requires further validation through larger clinical trials. 45 In the post‐COVID era, a notable shift has occurred in semen collection practices, with many fertility clinics adopting at‐home semen collection protocols to reduce in‐clinic exposure and improve patient comfort. While home collection offers convenience, concerns remain regarding the potential impact of extended transport time, suboptimal temperature control, and delays in sample processing on sperm quality parameters, including motility and viability. 46 Studies have shown that delayed processing and improper transport conditions can negatively affect sperm function, ultimately reducing IUI success rates. 23 , 47 Recent evidence suggests that semen collected at home can retain acceptable quality if transported to the laboratory within approximately 1 h, with some data indicating that semen parameters might remain stable even when transport time extends up to 1.5–2 h. 48 Therefore, minimizing transport time remains critical, as prolonged intervals between collection and processing increase the risk of motility decline and suboptimal insemination outcomes. Additionally, the choice between using fresh and frozen sperm is another critical factor influencing treatment outcomes. Although frozen–thawed sperm is routinely used in donor insemination and offers logistical flexibility, it is associated with reduced motility and viability due to cryodamage during the freeze–thaw process. 24 , 48 Several studies report lower pregnancy rates with frozen sperm compared to fresh ejaculates, particularly in the context of IUI, although differences are less pronounced in IVF and ICSI settings. 25 , 49 , 50 Therefore, both semen collection logistics and sperm preservation methods must be carefully optimized when designing protocols for IUI and other ART procedures. Tailoring sperm preparation techniques to semen quality significantly improves IUI outcomes, especially in cases involving male factor infertility. Semen parameters play a pivotal role in determining the likelihood of success with IUI. However, the volume of inseminated semen has not been significantly associated with pregnancy rates. 46 The total sperm count within a processed specimen is consistently identified as a critical determinant of IUI outcomes. 47 Among semen parameters, total progressive motile sperm count demonstrates the strongest association with IUI success, surpassing sperm concentration per milliliter in predictive value. Several studies support the use of post‐wash TMSC of ≥10 million as a threshold for optimizing IUI success, 48 , 49 particularly in controlled ovarian hyperstimulation cycles for treating male subfertility. 50 Similarly, post‐wash sperm count has emerged as a significant predictor, with high motility levels consistently linked to better clinical outcomes. 32 The chance of achieving pregnancy diminishes notably when motile sperm counts fall below 5 million, especially among women with prolonged infertility exceeding 10 years. 30 , 51 Although motile sperm count is often emphasized, the evidence regarding total sperm count alone remains inconclusive. One study reported comparable pregnancy rates between individuals with normal (15.8%) and abnormal (15.2%) sperm counts; however, the abortion rate was substantially higher among those with abnormal counts (71.4% vs. 38.8%). 52 Similarly, a retrospective analysis found no statistically significant association between sperm count and IUI success. 53 Reported threshold values for TMSC in IUI outcomes vary widely across the literature. While some studies suggest successful pregnancies occur with TMSC as low as 0.3–1 million, 54 , 55 others report no live births when pre‐wash TMSC falls below 2 million. 56 Despite occasional favorable outcomes in cycles with TMSC under 10 million, 48 , 50 , 58 several studies consistently identify a minimum threshold of 5 million as a more reliable predictor of success. 29 , 57 , 59 Post‐wash TMSC thresholds and the corresponding clinical pregnancy rate per IUI cycle (Table  2 ) indicates that a total TMSC exceeding 10 million is a significant predictor of IUI success. Post‐wash TMSC thresholds and corresponding CPR per IUI cycle. Note : Values represent approximate pooled ranges reported across multiple observational studies and clinical cohorts. Thresholds are intended to support clinical decision‐making rather than replace individualized assessment. Abbreviations: CPR, clinical pregnancy rate; IUI, intrauterine insemination; IVF, in vitro fertilization; TMSC, total motile sperm count. Importantly, lifestyle and environmental factors can significantly affect semen volume and motility. Factors such as physical inactivity, smoking, alcohol consumption, exogenous steroid use, and certain comorbidities have been linked to decreased sperm quality. Interventions focusing on lifestyle modifications, nutritional optimization, and targeted clinical management have been shown to enhance sperm function, potentially increasing the success rates of IUI and other ART. 26 , 27 A post‐wash TMSC threshold of approximately 1 million has been reported across multiple studies as the minimum level at which pregnancy is still possible, with the lowest successful post‐wash count documented at 0.8 million. 29 , 34 , 60 Several studies indicate that pregnancy rates do not substantially increase when post‐wash counts exceed 4 million, supporting approximately 1 million as an important minimum threshold in selected couples, particularly those with ovulatory dysfunction and cervical factor infertility. 29 In addition, evidence consistently shows that TMSC is a key determinant of IUI success. Pregnancy rates decline when inseminated TMSC is <2 million, 38 and a post‐wash TMSC ≥5 million has been strongly associated with higher success rates. 61 One study reported optimal pregnancy rates with a TMSC threshold of 5 million combined with a post‐wash count of 1 million, particularly in ovulatory dysfunction and cervical factor infertility cases, 11 as shown in Table  2 . Overall, these findings support the clinical utility of both the minimum post‐wash count (approximately 1 million) and higher progressive post‐wash TMSC thresholds (≥5 million) in guiding IUI suitability and counseling. Abnormal sperm morphology has been associated with poorer reproductive outcomes, including higher miscarriage risk. In one study using WHO 5th edition morphology criteria, patients with normal morphology demonstrated a pregnancy rate of 16.9% and an abortion rate of 35.6%, whereas those with abnormal morphology showed a reduced pregnancy rate of 15.0% and a higher abortion rate of 46.4%. 52 These findings suggest a clear correlation between sperm morphology and both pregnancy and abortion rates. Another study that assessed morphology using strict Kruger criteria also reported significant differences in normal sperm morphology between couples who achieved pregnancy and those who did not, despite comparable age and infertility duration, both before and after sperm processing. 53 These findings suggest that morphology, whether assessed using WHO 5th edition or Kruger strict criteria, remains an important predictive parameter in IUI outcomes. 53 Sperm concentration, defined as the number of sperm per milliliter, has traditionally been considered an important semen parameter; however, current evidence indicates that concentration alone is less predictive of IUI success than progressive post‐wash TMSC. Several studies have reported no significant independent association between sperm concentration and IUI pregnancy rates. 47 Similarly, Findeklee et al. reported that sperm motility, concentration, and density did not influence IUI pregnancy outcomes. 63 Noujua‐Huttunen et al. also found that the sperm concentration and density did not significantly influence IUI outcomes. 36 However, studies have consistently demonstrated poorer outcomes when total progressive motile sperm count is <5 million post‐wash, reinforcing that TMSC is more clinically relevant than raw concentration alone. 62 Therefore, in cases of male factor infertility where progressive TMSC remains persistently low and pregnancy is not achieved after approximately three IUI cycles, couples might benefit from counseling regarding transition to alternative ART options. 62 The DNA fragmentation index (DFI) is a method used to assess DNA abnormalities in sperm. A DFI >30% is considered indicative of abnormal DNA integrity. 64 Higher DFI levels have been positively correlated with increased pregnancy loss rates, with reported loss rates of 27.3% for high DFI, 14.6% for moderate DFI, and 4.9% for low DFI. 65 Studies have reported lower biochemical pregnancy and delivery rates among couples with a DFI >30% than among those with a DFI ≤30%. 66 Sperm DNA fragmentation has been associated with challenges at conception, prolonged time to pregnancy, poor outcomes following stimulated IUI, and impaired embryo development. These findings suggest that sperm DNA damage can have significant implications for reproductive outcomes. 66 , 67 , 68 , 69 However, other studies have reported no significant differences in pregnancy outcomes on the basis of the DFI. 4 , 11 In cases of significant DNA damage, alternative in vitro fertilization techniques are more appropriate. Environmental and lifestyle factors also influence sperm DNA integrity. Notable contributors include exposure to radiation and heat, airborne pollutants, sexually transmitted infections, certain chemical agents and drugs, and being overweight or obese. 70 Therefore, addressing modifiable risk factors might help optimize DNA integrity and improve outcomes. For men with persistently elevated DFI, clinical pathways might include assessment for correctable causes (e.g., varicocele), targeted lifestyle optimization, and cautious consideration of antioxidant therapy. If high DFI persists despite intervention and multiple unsuccessful IUI cycles, transitioning to IVF/ICSI might be warranted. Recent meta‐analytic evidence further indicates that interventions to reduce DFI vary in effectiveness, with varicocelectomy showing the most substantial and sustained improvement at 6 months, FSH therapy demonstrating potential benefit, antioxidant effects remaining modest and inconsistent, and lifestyle modification requiring further high‐quality studies before firm recommendations can be established. 55 , 71

Several additional factors have been shown to significantly influence the success of IUI cycles and warrant further consideration. The method of ovarian stimulation plays a central role, with gonadotropins generally associated with higher pregnancy rates compared to clomiphene citrate or letrozole, albeit with an increased risk of multiple gestations. 30 Moreover, the underlying cause of infertility impacts treatment outcomes women with unexplained infertility or ovulatory disorders typically show better responses to IUI compared to those with endometriosis or tubal factor infertility. 31 , 76 Ovarian reserve markers, such as anti‐Müllerian hormone antral follicle count, and baseline FSH, are also important predictors of ovarian responsiveness and overall treatment prognosis. 2 , 32 Racial and ethnic disparities in access to care, insurance coverage, and treatment success have been documented, highlighting the need for culturally sensitive and equitable fertility care. 33 , 34 , 78 , 79 , 80 Expanding our understanding of these multifactorial influences is essential for personalizing treatment strategies and improving reproductive outcomes across diverse patient populations. The duration of infertility, stimulation protocols used, cause of infertility, number of treatment cycles, timing of insemination, number of preovulatory follicles on the day of hCG administration, TMSC exceeding 10 million, and insemination count greater than 1 × 10 6 with more than 4% normal sperm morphology are reported to affect the success rate of IUI. 2 When considering the IUI methods used, the deliberate use of a modified slow‐release method for processed semen seems to notably increase clinical pregnancy rates following IUI with homologous semen. 77 Further, studies reveal the importance of a personalized prognostic score to be applied to each couple to customize their expectations and improve the quality of counseling provided to prevent disappointment. 78 In terms of psychological support, hope therapy for couples receiving IUI can positively affect their mood, increase fertility‐related attitudes, and increase pregnancy rates while reducing symptoms of depression, anxiety, and obsessive‐compulsive tendencies. 79 , 80 , 81 Optimal IUI outcomes depend on hormonal and procedural factors. An estrogen concentration >500 pg/mL on the day of hCG administration 29 and the use of gonadotropins with low‐dose protocols are associated with improved success rates, minimizing risks such as multiple pregnancies and ovarian hyperstimulation syndrome. 80 Compared with clomiphene citrate, gonadotropins are associated with higher live birth rates (52%) (41%) (relative risk: 1.24, 95% confidence interval: 1.05–1.46). 82 A recent systematic review reveals that among currently used IUI add‐ons, only vaginal luteal phase progesterone support shows probable benefit in improving live birth and ongoing pregnancy rates, while most other add‐on interventions, including endomentrial scratch, ovarian follicular phase stimulation, double insemination misoprostol, oxytocin, and bed rest after the IUI, lack sufficient evidence to support their routine clinical use and require further high‐quality research. 83 Procedurally, the use of a soft catheter enhances outcomes, whereas the use of vaginal progesterone gel or micronized progesterone significantly improves clinical pregnancy rates. 82 The timing between sperm preparation and IUI does not significantly affect success, even with waiting periods of up to 3 h. 83 , 84 Figure  1 summarizes the key findings discussed in this review. Determinants of the success rate of intrauterine insemination. BMI, body mass index; IUI, intrauterine insemination.

This review has several limitations. The included studies varied widely in design, sample size, and IUI protocols, contributing to potential heterogeneity. Most were retrospective, limiting control over confounding factors. Differences in semen analysis methods and reporting of key parameters, such as motility and morphology, could have influenced comparability. Importantly, no formal risk‐of‐bias assessment was conducted, and the possibility of publication bias and exclusion of non‐English studies cannot be ruled out. Heterogeneity in infertility diagnosis categories (e.g., unexplained infertility, endometriosis, and male factor) also limits direct comparability across studies, as do differences in reporting at the cycle level versus couple level. Standardized, prospective studies are needed to validate these findings and refine clinical thresholds for IUI success.

Kasuni Akalanka solely conceived and designed the study, conducted the literature search and data analysis, interpreted the findings, and drafted and revised the manuscript. The author approved the final version for publication and is accountable for all aspects of the work.

This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

Studies of various designs that evaluated factors associated with IUI success were thoroughly reviewed. Eligible studies included case studies, parallel group and crossover randomized controlled trials (RCTs), meta‐analyses, and retrospective observational studies. Studies of any design were included if they investigated patient‐related or cycle‐specific predictors of IUI outcomes, particularly the clinical pregnancy rate. A comprehensive literature search was performed via PubMed and Google Scholar to identify relevant articles published between 20 January 2000 and 20 March 2024. The search strategy employed combinations of Medical Subject Headings (MeSH) terms and free‐text keywords, such as “intrauterine insemination,” “IUI,” “predictive factors,” “success rate,” “sperm parameters,” “total motile count,” “number of follicles,” “endometrial thickness,” “BMI,” “alcohol consumption,” “smoking,” “nutritional factors,” “maternal factors,” and “paternal factors.” The search results were screened by title and abstract, and potentially eligible articles were reviewed in full text. The reference lists of the included articles were manually searched to identify any additional relevant studies. Studies were included if they: Reported factors influencing IUI success rates Presented original data or meta‐analytic findings Were published in English between 2000 and 2024 Focused on human subjects receiving IUI treatment. Reported factors influencing IUI success rates Presented original data or meta‐analytic findings Were published in English between 2000 and 2024 Focused on human subjects receiving IUI treatment. Studies were excluded if they: Lacked relevant outcome measures (e.g., clinical pregnancy) Focused solely on donor insemination without analyzing patient‐specific predictors Were expert opinions, or editorials. Lacked relevant outcome measures (e.g., clinical pregnancy) Focused solely on donor insemination without analyzing patient‐specific predictors Were expert opinions, or editorials. Data extracted from each included study encompassed study design, population characteristics, IUI protocol details, and identified predictors of clinical pregnancy. A qualitative synthesis approach was used to summarize and compare key themes and patterns across studies. Where available, quantitative indicators such as odds ratios, confidence intervals, or correlation coefficients were presented descriptively to illustrate the strength and direction of associations without performing statistical pooling.

A total of 180 out of 1670 identified articles were reviewed, and 89 met the inclusion criteria for this review. The data were synthesized based on clinically relevant categories: patient‐related, male‐related, female‐related, procedural, and environmental factors. Table  1 provides a comprehensive overview of the extracted data, and the results are discussed according to each section. Summary of modifiable and non‐modifiable determinants associated with IUI success. Note : Thresholds reflect ranges commonly reported across multiple observational and cohort studies evaluating predictors of IUI success. Values are intended to guide clinical interpretation rather than serve as absolute eligibility criteria. Modifiability refers to the extent to which each determinant can be influenced through lifestyle, medical, or clinical intervention. Thresholds and impact levels are based on evidence from multiple studies and represent the most commonly cited parameters associated with IUI success. Clinical application should be individualized based on patient characteristics and treatment protocols. Overweight and obesity are well‐established factors associated with subfertility in both women and men. In women, an elevated BMI has been linked to menstrual irregularities, oligo‐ovulation, and other reproductive disturbances. 4 , 5 While some studies suggest a positive relationship between higher BMI and pregnancy rates, 6 , 7 others report no significant association or even a detrimental effect, particularly when BMI exceeds 25–30 kg/m 2 . 8 , 10 In men, both overweight and obesity have been associated with reduced fertility potential. An increased BMI correlates with impaired semen quality, including lower ejaculate volume, decreased sperm concentration, reduced TMSC, and abnormal morphology. These negative effects are particularly evident in men with a BMI ≥30 kg/m 2 . 11 In the context of IUI treatment, obese women often require higher doses of gonadotropins to achieve adequate follicular stimulation, 7 , 11 potentially influencing treatment success. This suggests that excess body weight might negatively influence ovarian responsiveness during IUI cycles, resulting in suboptimal follicular development, prolonged stimulation duration, and higher medication burden. Further, impaired endocrine function, altered follicular environment, and insulin resistance frequently observed in women with elevated BMI might further compromise ovarian response, making it more challenging to achieve optimal cycle parameters required for successful IUI outcomes. The relationship between BMI and IUI pregnancy rates remains inconsistent throughout the literature. Some reports indicate that a BMI of 25–29.99 kg/m 2 does not negatively affect live birth rates, 8 , 10 yet other studies highlight reduced pregnancy rates among women with BMI >25 kg/m 2 . For example, a retrospective analysis revealed a significantly lower pregnancy rate of 1.6% in women with BMI >25 kg/m 2 compared to 7.2% in those with BMI <25 kg/m 2 . 7 , 11 , 12 Nonetheless, some investigations have not demonstrated a clear link between elevated maternal BMI and IUI pregnancy rates, 13 and others report no significant impact of maternal or paternal BMI on IUI outcomes. 14 Further, obesity has been linked to increased risk of biochemical pregnancy following IUI. 11 , 12 Overall, although findings vary across studies, the prevailing evidence suggests that excess body weight impairs fertility outcomes in both women and men, potentially affecting natural conception and ART such as IUI. These observations underscore the importance of considering BMI in fertility management. Nutritional factors directly influence reproductive health and consequently affect the success of IUI. Dietary patterns characterized by higher intake of polyunsaturated fatty acids (PUFAs), folate, fiber, starch, and adherence to a Mediterranean‐style diet have been associated with improved fertility outcomes in women, whereas trans‐saturated fatty acids have been linked to adverse reproductive effects, including endometriosis and ovulatory dysfunction. 15 Studies have indicated that several micronutrients, including zinc, selenium, folate, and vitamins B12, A, E, and C, as well as trace elements such as nickel and manganese, are critical for optimal spermatogenesis. In addition to micronutrients, macronutrients substantially influence male reproductive parameters. Docosahexaenoic acid (DHA), a PUFA, has been shown to positively affect sperm morphology and function; tuna oil, which is rich in DHA, serves as a valuable supplement. Additionally, arginine has been associated with improved sperm count and motility and can be sourced from seafood, watermelon juice, nuts, meats, and soy proteins. Collectively, these nutrients have significant effects on spermatogenesis, sperm concentration, motility, morphology, and overall semen quality. 16 However, direct evidence linking specific micronutrient intake to IUI pregnancy rates remains limited, with most available studies reporting associations through intermediate fertility markers rather than IUI‐specific clinical outcomes. Although the role of vitamin D in fertility has been extensively studied, a recent cross‐sectional study indicated that vitamin D levels appear not to significantly influence IUI success rates. 17 A nutritionally balanced diet, rich in both macro‐ and micronutrients, not only supports overall health but also enhances reproductive function. Further, diet serves as a key modulator of the gut microbiome, which has been shown to influence metabolic, hormonal, and reproductive health in women. 10 Therefore, regular consumption of nutrient‐rich foods, including fish, shellfish, meat, poultry, nuts, beans, seeds, carrots, pumpkins, and a wide variety of fruits and vegetables, is likely to support metabolic, reproductive health and contribute to better fertility outcomes. Abstinence from smoking and alcohol prior to and throughout IUI treatment has been associated with improved reproductive parameters, thereby potentially enhancing IUI success. It has been reported that smoking in both partners reduces the success rate of IUI. Therefore, stopping or at least reducing smoking is recommended to increase the likelihood of IUI success. 14 Smokers need higher doses of gonadotropins than nonsmokers do to obtain successful results from IUI, 19 and adverse effects of male smoking have been reported. 20 The underlying mechanism is presumed to involve a toxic effect of various tobacco chemicals on follicular development, gamete mutagenesis, or inhibition of granulose cell aromatase. This, in turn, leads to accelerated follicular depletion, reduced fecundity, increased miscarriages, and accelerated onset of menopause. 21 Tobacco use, whether smoked or chewed, poses immediate and long‐term health risks, including carcinogenic effects. Nicotine, a highly addictive compound, can cause withdrawal symptoms such as anxiety and irritability. Reducing both active and passive tobacco exposure is associated with improved fertility and better pregnancy outcomes. Evidence on lifestyle factors remains inconsistent. While some observational studies have reported that moderate consumption of coffee, tea, or alcohol is associated with higher pregnancy and live birth rates, others have shown no significant effect on IUI outcomes. These findings should therefore be interpreted as hypothesis‐generating, and further investigation warranted to clarify potential confounding and underlying mechanisms. 22 , 23 The evidence indicates that modifying male habits and work conditions can improve IUI outcomes, as studies report avoiding smoking, alcohol, and heat exposure before and during treatment increases success rates. 24 While most studies have shown reduced sperm quality, concentration, motility, and morphology among smokers, a definitive causal link to infertility is unclear. Nevertheless, male smoking is associated with significantly lower clinical pregnancy rates. 25 Although no strong link has been found between low‐to‐moderate alcohol intake or binge drinking and IUI success, further research is needed to confirm these findings. 26 Fertility challenges have a substantial psychological impact. Dealing with fertility problems negatively affects the psychological well‐being of the majority of couples. Treatment options are reportedly associated with psychological symptoms such as anxiety, depression, and irritability. 27 Ovulation induction agents used in IUI protocols (e.g., gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors) might further contribute to anxiety, irritability, and depressive symptoms through central effects on the hypothalamic–pituitary axis. 12 The evidence linking psychological distress directly to IUI pregnancy outcomes, however, remains mixed. Some studies have not demonstrated a significant association between anxiety levels and clinical pregnancy rates following IUI. 28 Nevertheless, biological and mechanistic data indicate that elevated stress might adversely influence fertility potential by increasing cortisol levels, disrupting gonadotropin‐releasing hormone pulsatility, impairing luteinizing hormone/follicular stimulating hormone (FSH) secretion, and reducing endometrial receptivity and implantation potential. 11 , 13 Stress‐related immune dysregulation and pro‐inflammatory cytokine activation might further compromise reproductive physiology. 14 Therefore, while clinical evidence remains inconsistent, the biological plausibility of stress‐related impairment in reproductive function supports the importance of psychological support and stress management prior to and during treatment. Reducing stress might improve emotional coping, reduce treatment burden, and help decrease the number of cycles required to achieve pregnancy, potentially reducing the need for escalation to more invasive ART procedures. 11 , 15

The number of follicles has a linear relationship with pregnancy rate, and increasing follicle numbers are associated with higher IUI success. 18 , 32 , 55 , 71 A retrospective cross‐sectional study also demonstrated that the duration of infertility had a highly significant impact on pregnancy rate and confirmed a positive correlation between the number of preovulatory follicles and pregnancy outcomes. 32 However, this benefit must be considered alongside clinical risk. When endometriosis or tubal factor infertility contributes to subfertility, these conditions negatively influence IUI pregnancy rates. 18 Multifollicular development, especially in cycles stimulated with gonadotropins, increases the risk of multiple gestations, including twins and higher‐order multiples, which in turn increases the likelihood of obstetric complications such as preterm birth and low birth weight. 28 Additionally, the risk of ovarian hyperstimulation syndrome, although less frequent in IUI compared with IVF, rises when excessive follicular development occurs. 29 , 74 Therefore, while increasing follicle numbers improves pregnancy probability, this must be balanced against safety considerations. Many centers adopt a conservative policy for young women (<35 years), recommending cycle cancellation or conversion to IVF if ≥3 mature follicles are present, while slightly higher follicle thresholds might be acceptable in older women due to reduced multiple pregnancy risk. Further, luteal phase support has been shown to improve outcomes in stimulated IUI cycles. The use of vaginal progesterone gel or micronized progesterone significantly increases clinical pregnancy rates and can positively influence live birth rates, particularly when gonadotropins are used for ovulation induction. 72 Optimizing follicle development must, therefore, involve careful age‐based thresholds, stimulation dose adjustments, and meticulous monitoring to maximize benefit while minimizing maternal and fetal risks. Endometrial thickness (ET) is an important marker of endometrial receptivity in IUI cycles. Evidence suggests that ET below approximately 6 mm is associated with reduced pregnancy rates, whereas within the range of 6–10 mm, pregnancy likelihood appears to be more favorable. 31 , 32 , 75 A secondary analysis of IUI cycles for unexplained subfertility also demonstrated that although the mean ET was 7.2 ± 1.8 mm, differences between pregnant and non‐pregnant groups within this range were small, and the association between ET and ongoing pregnancy was not statistically significant. 73 , 74 This aligns with meta‐analytic findings indicating that once ET exceeds approximately 6 mm, variations within 6–10 mm have limited predictive value, while data beyond 10 mm remain mixed and inconclusive. Age‐related changes in ET have also been described, with thinner endometrium more frequently observed in older women. 75 Lifestyle and nutritional optimization, such as diets enriched with vitamin E and arginine, might support endometrial perfusion and hormonal regulation, potentially improving ET. 76 Overall, ET <6 mm might signal poorer prognosis, while values between 6 and 10 mm appear clinically acceptable for IUI, but thresholds above this range require cautious interpretation.

The success of IUI is governed by the interplay of modifiable and clinical determinants. Optimizing maternal BMI, nutritional status (including adequate folate, zinc, selenium, and antioxidant vitamins), and psychological well‐being, alongside cessation of smoking and alcohol use, might improve treatment outcomes. Clinically, achieving an endometrial thickness of 6–10 mm, attaining a post‐wash TMSC ≥5–10 million, and using gonadotropin‐based stimulation protocols are associated with higher pregnancy rates. Integrating individualized counseling, lifestyle modification, and precise clinical monitoring should, therefore, form a central component of fertility management. Future research should focus on developing predictive models that combine biological, behavioral, and procedural determinants to refine personalized, evidence‐informed, and cost‐effective IUI care.

Generative AI (ChatGPT, GPT‐5) was used solely for language refinement and readability enhancement of the manuscript. No AI tools were used for data extraction, statistical analysis, study selection, interpretation of findings, or scientific content generation.

Intrauterine insemination (IUI) is one of the widely used assisted reproductive technologies (ART), particularly for couples with unexplained infertility, mild male factor infertility, anovulation, or cervical factor infertility. The procedure involves placing processed, motile sperm directly into the uterine cavity to enhance the likelihood of fertilization by bypassing cervical barriers and optimizing sperm–oocyte proximity. 1 , 2 As a less invasive and more affordable alternative to in vitro fertilization (IVF), IUI is often the first‐line treatment in couples with favorable prognostic indicators. Despite improvements in ovarian stimulation protocols and procedural techniques, IUI success rates remain modest and variable, ranging from 5% to 25% per cycle. 3 , 4 This heterogeneity is influenced by a combination of factors, including differences in cycle type (natural vs. stimulated), sperm source (partner vs. donor), female age, and semen quality, as well as underlying biological, clinical, and lifestyle determinants. 3 , 5 , 6 , 7 Common predictors of success include maternal age, total motile sperm count (TMSC), the number of mature follicles, endometrial thickness, and duration of infertility. 8 , 9 Emerging evidence has also emphasized the role of modifiable risk factors in influencing reproductive outcomes. Elevated body mass index (BMI) is associated with anovulation, impaired endometrial receptivity, and hormonal imbalances; however, its direct effect on IUI outcomes remains inconclusive. 10 , 11 , 12 , 13 Similarly, tobacco use and alcohol consumption negatively affect both male and female reproductive parameters, including sperm motility and ovarian reserve. 14 , 15 , 16 Nutritional factors, particularly folate, zinc, selenium and antioxidant vitamins, are known to influence spermatogenesis and endometrial receptivity, serving as important preconception fertility markers. While these nutrients might indirectly contribute to improved chances of conception, direct evidence linking specific micronutrient deficiencies to IUI success rates remains limited and heterogeneous. 17 , 18 Psychological factors such as elevated stress and anxiety have been associated with reduced treatment adherence and lower clinical efficacy, although the underlying biological mechanisms remain poorly understood. 19 Environmental and occupational exposures, including air pollution, pesticides, and endocrine‐disrupting chemicals, are also emerging as significant contributors to impaired reproductive outcomes and reduced IUI success rates. 20 , 21 In addition, clinical and procedural variables, such as the choice of ovarian stimulation protocol (gonadotropins vs. clomiphene), use of luteal phase support, timing of insemination, and insemination technique (slow‐release vs. bolus), have been shown to influence pregnancy outcomes. 22 , 23 , 24 Given the multifactorial nature of IUI success and the heterogeneity across published studies, there is a clear need for an integrative synthesis to inform clinical decision‐making and individualized patient counseling. This review critically examines the biological, clinical, lifestyle, and environmental determinants of IUI success, with particular emphasis on modifiable factors and their potential to enhance treatment outcomes. The aim is to provide a comprehensive, evidence‐based framework to support personalized fertility care and improve reproductive success.

I have no conflicts of interests to declare.

Female age was consistently reported as the strongest predictor of IUI success. Continuing pregnancy rates were shown to be 38.5% for women 40 years of age, and twin pregnancy rates also decrease significantly after 30 years. 29 One report indicated that pregnancy rates for women between 19 and 40 years were approximately 10% and declined sharply beyond 40 years. 30 Multiple studies confirm this negative correlation, demonstrating that IUI success declines as maternal age increases. 31 , 32 According to Patsama et al. (2015), the biochemical pregnancy rate decreased from 27.6% in women 40 years. 33 Other studies similarly reported marked reductions in per‐cycle pregnancy rates in women ≥40 years (4.1%–7%) compared with 13.7–17% in women 45 years. 38 A prospective cohort study reported a steep decline after 37 years and recommended consideration of earlier transition to IVF in older women to avoid repeated failed IUI attempts. 16 Consistent with this, American Society for Reproductive Medicine guidelines indicate that IUI effectiveness is significantly limited in women over 40 years, and alternative ART strategies should be prioritized. 17 The biological mechanism underlying this decline is attributed to a progressive reduction in oocyte quantity and quality, higher rates of aneuploidy, and diminished endometrial receptivity with advancing age. 18 Collectively, these findings underscore the strong age dependency of IUI outcomes and highlight the need for timely fertility planning and age‐appropriate counseling, particularly among couples postponing childbearing. 29 , 36 Increasing paternal age, particularly when it exceeds 40 years, has an impact on reproductive outcomes, such as an increased incidence of premature birth, 39 abortions, 40 autism spectrum disorders, 41 and infertility. 42 There was no effect of paternal age on pregnancy or miscarriage rates among men aged 25–56 years (mean male age 34.3 years) who did not have severe male factor infertility. 43 Compared with men aged 35 years have a decreased pregnancy rate. 44 In contrast, another study demonstrated that age does not appear to greatly affect the pregnancy rate of male partners, although after the age of 50, there are more sperm abnormalities. 45 Advancing paternal age has also been associated with increased sperm DNA fragmentation and higher levels of sperm aneuploidy, which might negatively influence reproductive potential and warrants consideration during counseling. Therefore, as subfertility is increasingly prevalent in modern societies, couples should be advised to avoid unnecessary delays in childbearing where possible, as age‐related reproductive decline is a modifiable factor only when childbearing postponement is elective.