Impact of conventional cigarette and electronic cigarette use on sperm quality and IVF/ICSI outcomes.

The demographic characteristics of male participants showed no significant differences (Table  1 ). Similarly, there were no significant differences in age and body weight among the female participants. However, the average BMI of the female partners in the conventional cigarette group was higher than that of the E-cigarette group (23.38 ± 4.29 vs. 22.16 ± 3.47, p  = 0.017) (Table  2 ). The distribution of female infertility factors was similar between the conventional and electronic cigarette groups. In the conventional group, 61.59% of female partners had anovulation (including PCOS, thyroid dysfunction and hyperprolactinemia), 14.57% had tubal factor infertility, and 23.18% were categorized as IUI failure. In the electronic cigarette group, the respective proportions were 64.83%, 11.72%, and 23.45%. One patient in the conventional group had both anovulation and tubal factors. There was no statistically significant difference in the distribution of female infertility factors between the two groups ( p  = 0.673, chi-square test) (Table  3 ). Table 1 Baseline and clinical characteristics of males in the conventional cigarette group and the E-cigarette group. Characteristics Conventional cigarette E-cigarette p -value Age 35.54 ± 3.78 35.61 ± 3.70 0.871 BMI (kg/m 2 ) 26.64 ± 3.49 25.98 ± 3.27 0.118 Weight (kg) 82.08 ± 11.99 80.64 ± 10.86 0.315 Serum LH (mIU/mL) 5.34 ± 2.16 5.07 ± 2.32 0.78 Serum FSH (mIU/mL) 4.95 ± 2.42 5.50 ± 3.61 0.21 Serum prolactin (ng/mL) 13.84 ± 5.97 13.02 ± 4.80 0.029 Serum testosterone (ng/mL) 4.57 ± 2.82 3.90 ± 1.62 0.46 Serum free testosterone (pg/mL) 9.80 ± 2.14 8.87 ± 2.89 0.1 Serum SHBG (nmol/L) 31.68 ± 12.74 27.71 ± 12.49 0.81 Semen volume (mL) 2.87 ± 1.42 2.66 ± 1.46 0.902 Sperm concentration (×10⁶/mL) 81.55 ± 57.19 71.78 ± 44.40 0.007 Sperm motility (%) 48.15 ± 13.29 48.91 ± 11.75 0.014 Semen WBC 0.33 ± 1.01 0.25 ± 0.62 0.115 Strict morphology (%) 1.76 ± 0.79 1.76 ± 0.77 0.498 E-cigarette, electronic cigarette; BMI, body mass index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; SHBG, sex hormone binding globulin, WBC, white blood cell. Baseline and clinical characteristics of males in the conventional cigarette group and the E-cigarette group. E-cigarette, electronic cigarette; BMI, body mass index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; SHBG, sex hormone binding globulin, WBC, white blood cell. There were no statistically significant differences in the serum levels of LH, FSH, testosterone, free testosterone, and sex hormone binding globulin (SHBG) between the two groups. However, the serum prolactin levels were significantly higher in the conventional cigarette group than in the E-cigarette group (13.84 ± 5.97 vs. 13.02 ± 4.80, p  = 0.029) (Table  1 ). In the analysis of semen parameters, there were no significant statistical differences observed in semen volume, white blood cell (WBC) count in semen, and sperm morphology between the two groups. However, a significant difference was observed in sperm concentration between the conventional cigarette group and the E-cigarette group (81.55 ± 57.19 vs. 71.78 ± 44.40, p  = 0.007). Similarly, sperm motility was notably lower in the conventional cigarette group compared to the E-cigarette group (48.15 ± 13.29 vs. 48.91 ± 11.75, p  = 0.04). Contrary to the common belief that conventional cigarette use is more harmful to reproductive function, the sperm concentration was higher in the conventional cigarette group, while sperm motility was better in the E-cigarette group (Table  1 ). In the analysis of female hormone profiles, levels of AMH, day 3 E2, day 3 LH, and day 3 FHS levels were measured, revealing no significant differences between the two groups (Table  2 ). Table 2 Baseline and clinical characteristics of female partners in the conventional cigarette group and the E-cigarette group. Characteristics Conventional cigarette E-cigarette p -value Age 33.78 ± 3.04 33.29 ± 2.85 0.085 BMI (kg/m 2 ) 23.38 ± 4.29 22.16 ± 3.47 0.017 Weight (kg) 61.53 ± 11.68 58.53 ± 9.9 0.053 Infertility duration (months) 28.19 ± 22.87 26.03 ± 22.17 0.933 Infertility type Primary 64.9% (98) 70.34% (102) 0.462 Secondary 35.1% (53) 29.66% (43) Parity Nullipara 92.05% (139) 92.41% (134) 0.24 Primipara 7.95% (12) 7.59% (11) AMH (ng/mL) 4.57 ± 3.06 5.04 ± 3.63 0.284 Day 3 E2 (pg/mL) 37.41 ± 17.46 38.95 ± 19.35 0.434 Day 3 LH (mIU/mL) 6.52 ± 3.66 7.21 ± 8.17 0.185 Day 3 FSH (mIU/mL) 7.32 ± 4.91 6.84 ± 2.25 0.419 Stimulation duration (days) 9.61 ± 1.52 9.44 ± 1.72 0.496 Total gonadotropin dose (IU) 2385.68 ± 1047.71 2338.45 ± 898.18 0.382 AFC 17.82 ± 9.89 18.12 ± 10.74 0.753 Total number of retrieved oocytes 19.19 ± 10.29 19.76 ± 10.67 0.449 Number of 2PN 11.23 ± 7.00 11.28 ± 6.75 0.52 E-cigarette: Electronic cigarette; BMI: Body Mass Index; AMH: AntiMüllerian Hormone; E2: Estradiol; LH: Luteinizing Hormone; FSH: Follicle-Stimulating Hormone; AFC: Antral Follicle Count; 2PN: Two Pronuclei. Baseline and clinical characteristics of female partners in the conventional cigarette group and the E-cigarette group. Parity Nullipara E-cigarette: Electronic cigarette; BMI: Body Mass Index; AMH: AntiMüllerian Hormone; E2: Estradiol; LH: Luteinizing Hormone; FSH: Follicle-Stimulating Hormone; AFC: Antral Follicle Count; 2PN: Two Pronuclei. There were no significant differences between the conventional cigarette group and the E-cigarette group (Table  2 ), which may be attributed to the similar female age, AMH levels, and AFC across both groups. There were no significant statistical differences between the E-cigarette group and the conventional cigarette group in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and biochemical miscarriage rate (Table  4 ). However, the clinical miscarriage rate was significantly higher in the conventional cigarette group than in the E-cigarette group (36.27% vs. 11.96%, p  = 0.000). Similarly, the live birth rate was significantly higher in the E-cigarette group (55.86% vs. 41.06%, p  = 0.011). This suggests that the likelihood of miscarriage after pregnancy confirmation via ultrasound is lower in the E-cigarette group compared to the conventional cigarette group. Table 3 Distribution of female infertility causes between conventional and E-cigarette groups. Female infertility causes Conventional cigarette E-cigarette Alovulatory 61.59% (93/151) 64.83% (94/145) Tubal factor 14.57% (22/151) 11.72% (17/145) Prior IUI failure 23.18% (35/151) 23.45% (34/145) Combined (anvulatory + tubal) 0.66% (1/151) 0% (0/145) E-cigarette, electronic cigarette; IUI, intrauterine insemination. Distribution of female infertility causes between conventional and E-cigarette groups. E-cigarette, electronic cigarette; IUI, intrauterine insemination. Table 4 Pregnancy outcome rates between the conventional cigarette group and the E-cigarette group. Outcome Conventional cigarette E-cigarette p -value BC pregnancy rate 78.81% 76.55% 0.641 Clinical pregnancy rate 67.55% 63.45 0.458 Ongoing pregnancy rate 49.01% 56.55% 0.158 BC miscarriage rate 14.29% 17.12% 0.556 Clinical miscarriage rate 36.27% 11.96% 0.000 Live birth rate 41.06% 55.86% 0.011 E-cigarette, electronic cigarette; BC, biochemical. Pregnancy outcome rates between the conventional cigarette group and the E-cigarette group. E-cigarette, electronic cigarette; BC, biochemical. The live birth rate is the most critical and definitive measure of IVF outcomes. To identify predictors of successful live births in IVF cycles involving smoking male partners, univariate and multivariate logistic analyses were conducted. As shown in Table  5 , univariate analysis indicated that male BMI, male serum FSH levels, parity, and the number of 2PN embryos are predictors of live birth. In the multivariate analysis, male serum FSH levels and the number of 2PN embryos were found to significantly influence the likelihood of a successful live birth. Table 5 Predictors of successful live birth in couples undergoing IVF with smoking male partners. Parameters Univariate analysis Multivariable analysis OR (95% CI) p -value OR (95% CI) p -value Male age 1.04 (− 0.094 – −0.033) 0.271 Male BMI 0.938 (− 0.141–0.009) 0.09 0.94 (0.87–1.017) 0.123 Serum LH 1.092 (− 0.032–0.219) 0.133 Serum FSH 1.203 (0.091–0.307) 0.001 1.19 (1.06–1.336) 0.004 Serum prolactin 1.05 (− 0.006–0.119) 0.101 Semen concentration 0.996 (− 0.009–0.001) 0.12 Sperm motility 0.982 (− 0.036–0.001) 0.059 0.99 (0.97–1.011) 0.35 Female age 0.994 (− 0.083–0.081) 0.88 Female BMI 0.979 (− 0.077–0.041) 0.472 Parity 0.449 (− 1.783–−0.155) 0.048 0.57 (0.24–1.338) 0.194 AMH 1.036 (− 0.031–0.109) 0.316 Total number of retrieved oocytes 1.018 (− 0.004–0.042) 0.110 1.04 (1.00–1.08) 0.051 Number of 2PN 1.05 (0.014–0.096) 0.007 0.19 (0.05–0.705) 0.013 OR, odds ratio; CI, confidence interval; BMI, body mass index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; AMH, antimüllerian hormone; 2PN, 2-pronucleus. Predictors of successful live birth in couples undergoing IVF with smoking male partners. OR, odds ratio; CI, confidence interval; BMI, body mass index; LH, luteinizing hormone; FSH, follicle-stimulating hormone; AMH, antimüllerian hormone; 2PN, 2-pronucleus.

Between May 2022 and January 2024, a total of 151 conventional cigarette smokers and 145 E-cigarette smokers, all undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at a single infertility clinic, were retrospectively enrolled. This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by Institutional Review Board and Ethics Committee of CHA University College of Medicine (2023-06-009-001). The requirement for written informed consent was waived by the Ethics Committee of CHA University College of Medicine due to the retrospective nature of the study. Clinical assessments of the male partners included age, height, body weight, type of smoking, amount of smoking, medical history, physical examination, semen analysis, and hormone profiles. For the female partners, the collected data included age, height, body weight, presence of underlying diseases, duration of infertility, parity, and various IVF parameters such as anti-Müllerian hormone (AMH) levels, basal levels of IVF hormones (estradiol (E2), follile-stimulating hormone (FSH), and luteinizing hormone (LH)), basal antral follicle count (AFC), and the total number of oocytes retrieved. Finally, we analyzed obstetrical outcomes. To ensure consistent exposure, only male participants who had exclusively used either conventional or electronic cigarettes for at least six consecutive months prior the semen analysis and ART procedures were included in the study. The study focused on couples whose infertility was primarily due to tubal factors, polycystic ovarian syndrome (PCOS), abnormal thyroid function, hyperprolactinemia and failed intrauterine insemination (IUI). These conditions were defined using standard diagnostic criteria. Polycystic ovarian syndrome was diagnosed based on the Rotterdam criteria, requiring at least two of the following: oligo- or anovulation, clinical and/or biochemical hyperandrogenism, and polycystic morphology on ultrasound 12 . Thyroid dysfunction encompasses both hypothyroidism and hyperthyroidism, and was diagnosed according to the laboratory reference ranges for thyroid stimulating hormone (TSH) and free thyroxine (fT4) 13 . Lastly, hyperprolactinemia was defined as a serum prolactin level exceeding 20 ng/mL on at least two occasions 14 . This criterion was applied to female participants, not to male participants. All embryo transfer cycles involved frozen/thawed embryo transfer, and only the first or second embryo transfer attempts were included to eliminate factors related to recurrent implantation failure. Couples with additional infertility factors, such as poor ovarian response, endometriosis, adenomyosis, recurrent pregnancy loss, recurrent implantation failure, women over the age of 38, and congenital genitourinary abnormalities of either partner were excluded from this study. In particular, male partners with oligoteratozoospermia, severe asthenospermia (defined as < 32% progressive motility) 15 , varicocele, or azoospermia, were excluded. Men with a history of surgeries that affect reproductive function, such as vasectomies or inguinal surgeries, were excluded. Additionally, all female participants were nonsmokers. Poor ovarian response was defined in accordance with the Bologna criteria. According to the Bologna criteria, at least two of the following are required: (1) advanced maternal age (≥ 40 years) or other risk factors for poor ovarian response; (2) a previous cycle with ≤ 3 oocytes retrieved using a conventional stimulation protocol; or (3) abnormal ovarian reserve test results, such as anti-Müllerian hormone (AMH) levels < 1.1 ng/mL or antral follicle count (AFC) < 7 16 . Endometriosis and adenomyosis were excluded as potential confounding factors due to their known impact on ovarian function and ART outcomes 17 , 18 . These conditions were diagnosed using radiologic modalities such as ultrasound and magnetic resonance imaging (MRI) or based on histopathologic findings. Sperm samples were collected from the male fertility clinic at CHA Ilsan Medical Center. Semen samples were obtained by masturbation following 2–7 days of sexual abstinence. All samples were placed in sterile containers and allowed to liquefy for at least 30 min at room temperature. They were then subjected to routine seminal analysis according to the WHO laboratory guidelines, 2010 15 . Specifically, this analysis evaluated semen volume, pH, sperm concentration, motility, vitality, and morphology. All female patients received a standard GnRH antagonist regimen starting in the early follicular phase of the menstrual cycle. Initially, all participants were administered either recombinant follicle-stimulating hormone (rFSH, Gonal-F; Merck Serono, Geneva, Switzerland), follitropin-delta (Rekovelle; Ferring, Malmö, Sweden), or a combination of FSH and LH, specifically human menopausal gonadotropin (hMG, Menopur; Ferring, Malmö, Sweden). The starting dose of gonadotropin was determined by clinicians based on age, BMI, and ovarian reserve. When the leading follicle reached a diameter of 13–14 mm, a GnRH antagonist (Cetrotide 0.25 mg, Merck Serono, Geneva, Switzerland) was administered to suppress a premature LH surge. When two or more leading follicles reached 18 mm in diameter, recombinant human chorionic gonadotropin (rhCG) (Ovidrel 250 µg, Merck Serono, Geneva, Switzerland) was administered to induce final oocyte maturation. Thirty-six hours after triggering, transvaginal ultrasound-guided oocyte retrieval was performed. For oocyte cryopreservation, metaphase II (MII) oocytes were selected, and ICSI was additionally performed for embryo cryopreservation. A freeze-all strategy was implemented for all enrolled cycles, and no preimplantation genetic testing was conducted. All transferred embryos were 5-day blastocysts. The primary outcome of this study was the pregnancy outcomes for each group. Biochemical pregnancy was defined as the presence of beta-human chorionic gonadotropin (β-HCG) detected in serum or urine. Clinical pregnancy was confirmed by ultrasound visualization of a gestational sac or other definitive clinical signs of pregnancy. Ongoing pregnancy was defined as the presence of at least one viable fetus after the 12th week of gestation. Biochemical miscarriage was diagnosed when a positive β-HCG test was present without evidence of a gestational sac. Clinical miscarriage was diagnosed when an intrauterine gestational sac detected by ultrasound failed to progress to a viable pregnancy. Live birth rate was defined as the number of deliveries that resulted in a live-born neonate 19 . Participants were divided into two groups based on the type of smoking reported by the male partners. Categorical variables were presented as percentages and compared using the chi-squared test. Continuous variables were analyzed using an independent t-test and presented as means with standard deviations. A p-value of 0.05 or less was considered statistically significant. The relationship between clinical parameters and live birth rates was analyzed using both univariate and multivariate logistic regression methods. Statistical analyses were conducted using SPSS version 21.0 (SPSS Inc., Chicago, IL, USA).

This retrospective study revealed that male partners who used E-cigarettes had lower prolactin levels compared to those who smoked conventional cigarettes. Attia et al. 20 compared hormone profiles between smoking and nonsmoking males, finding that serum E2 and serum prolactin levels were significantly higher in the smoking group, while serum total testosterone levels were similar. Wilkins et al. 21 demonstrated that chronic male smokers had increased levels of serum cortisol, growth hormone, and prolactin, which were associated with nicotine use. Their study indicated significant hormone elevation in high-dose nicotine users, suggesting that nicotine plays a predominant role in the hormonal changes associated with smoking. Conversely, another study found that serum prolactin levels were significantly lower in smoking males, suggesting that cyclicadenosine monophosphate produced by nicotine mediates changes in pituitary hormones. This study reported increased plasma cortisol levels and decreased plasma prolactin levels in smoking group 22 . In our study, the conventional cigarette group had significantly higher serum prolactin levels, suggesting either lower nicotine exposure or a different physiological response in the E-cigarette group. There are limited studies regarding the adverse effects of smoking on male reproductive fuction 23 . Rehman et al. 24 analyzed semen parameters in smoking and nonsmoking males, demonstrating significant decreases in total sperm count, sperm motility, and sperm morphology among smokers. Multivariable analysis confirmed that cigarette smoking significantly affected sperm count and morphology. Another study presented significant reductions in semen volume, total sperm count, sperm concentration, and motility among smokers. Additionally, this study observed increased sperm DNA fragmentation and teratozoospermia in smokers 25 . Additionally, a prospective, nonrandomized controlled trial demonstrated that quitting smoking for more than three months significantly improved semen volume, sperm concentration, and total sperm count 26 . Although there were positive effects on sperm motility and morphology, the improvements were not statistically significant. Our study revealed that sperm motility was significantly higher in the E-cigarette group compared to the conventional cigarette group. However, contrary to expectations, the total sperm count was higher in the conventional cigarette group. This discrepancy could be attributed to variations in tobacco composition and methods of inhalation. Conventional cigarettes contain harmful substances such as tar, acrolein, and formaldehyde, which cause DNA damage and oxidative stress 27 – 29 . In contrast, E-cigarette users inhale aerosols produced by heating chemicals, the interactions of which are not fully understood 5 . Further research is required to clarify the different impacts of conventional cigarettes and E-cigarettes on male reproductive function. Serum levels of LH, FSH, and total testosterone are known to be associated with sperm motility. Specifically, serum LH and FSH levels are inversely associated with sperm count, motility, and morphology 30 , 31 . LH stimulates testosterone production in Leydig cells, while both LH and FSH regulate spermatogenesis in Sertoli cells. In both male and female cigarette users, serum FSH levels are significantly elevated 23 , 32 , suggesting that smoking increases these levels, which in turn negatively affects sperm parameters and potentially impacts clinical pregnancy outcomes. Poor semen parameters are known to negatively affect live birth rates achieved through ovulation induction, IUI, and IVF 33 . While our study found that serum FSH levels differed between groups, the observed values remained within clinically acceptable reference ranges. Therefore, these findings should be interpreted as descriptive rather than as indicative of pathologic findings. Because of the absence of a non-smoking control group or standard reference thresholds in our study, we do not draw causal conclusions regarding elevated serum FSH level and abnormal spermatogenesis. The increased risk of miscarriage among both male and female smokers is well established 34 , 35 . A retrospective cohort study on paternal smoking and spontaneous abortion reported an odds ratio (OR) of 1.17 (95% CI 1.16–1.19) for spontaneous abortion associated with paternal smoking, and an OR of 1.11 (95% CI 1.08–1.14) for paternal smoking during the periconceptional period 36 . In our study, the clinical miscarriage rate was significantly lower in the E-cigarette user group, suggesting that paternal use of E-cigarettes may pose a lower risk of miscarriage compared to conventional cigarette use. However, further research involving larger sample sizes and studies exploring the underlying mechanisms is necessary. This study has several strengths, such as its innovative design that compares conventional cigarettes and E-cigarettes, the evaluation of various sex hormones in both males and females, adjustments for potential confounders such as causes of infertility and types of embryo transfer, and the analysis of IVF and clinical pregnancy data. However, several limitations should be acknowledged. First the retrospective design and relatively small sample size limit causal inference. Data on alcohol use and recreational drugs (e.g., cannabis, cocaine, or amphetamines) were not collected, although their use is presumed to be rare in our population due to cultural and legal factors 37 – 40 . We also lacked information on dietary patterns and antioxidant supplementation, which may affect male infertility. Emerging evidence suggests that dietary factors, particularly antioxidant-rich foods such as fruits, vegetables, fish, nuts, and whole grains, may positively influence male fertility by improving sperm function and reducing oxidative stress 41 , 42 . Recent reviews have also highlighted that men undergoing infertility treatment may benefit from antioxidant supplementation and a diet favoring omega-3 fatty acids, although the optimal compounds and dosages remain unclear 42 , 43 . Unfortunately, due to the retrospective design of our study, we were unable to assess dietary patterns or supplement use in our population, and this limitation has now been acknowledged. In addition, E-cigarette aerosols have been reported to contain toxic heavy metals such as lead, nickel, and chromium 44 , which may negatively affect spermatogenesis 45 , 46 . Although we did not directly measure heavy metal levels in our participants, the potential for such exposure remains a concern. Furthermore, the smoking history of male partners was based on self-reported data, which may be subject to recall bias or underreporting, and we cannot exclude the possibility that some subjects may have previously switched between conventional and electronic cigarettes. Moreover, the study did not account for the specific type, generation, brand or flavor of E-cigarette used by participants. Given the rapid evolution of E-cigarette devices and their variability in nicotine delivery and chemical composition 47 , this heterogeneity may have influenced reproductive outcomes. We acknowledge this as a limitation and recommend that future prospective studies incorporate toxic exposure assessment and stratify users based on device characteristics to better elucidate the differential effects of various E-cigarette types. Although our pooled regression model identified several predictors of live birth across the entire study cohort, including male serum FSH levels and the number of 2PN embryos, these factors did not differ significantly between the conventional and E-cigarette groups. Thus, they are unlikely to fully explain the observed differences in live birth or clinical miscarriage rates. It is possible that other variables, such as sperm motility and serum prolactin 21 , 22 , 48 —which may differ significantly between groups—may have contributed to the improved outcomes in the E-cigarette group. However, we did not perform group-specific regression analyses due to limited statistical power, and this remains a limitation. Future studies with larger cohorts are warranted to investigate group-specific predictors in more depth. Additionally, the analysis did not take into account the amount and duration of smoking. Prospective studies with larger sample sizes and more comprehensive adjustments for confounding factors are needed to validate our findings.

To the best of our knowledge, this study is the first to compare the effects of conventional cigarettes and E-cigarettes on IVF outcomes. Our findings suggest that E-cigarette use by male partners during IVF may pose fewer risks compared to conventional smoking, particularly regarding semen motility, clinical miscarriage rates, and live birth rates in IVF/ICSI couples. However, it is crucial to emphasize that this should not be interpreted as an endorsement of E-cigarette use. Given that E-cigarettes are often perceived as an alternative to conventional smoking, further research is necessary to explore their effects on gamete quality and function to compare these impacts with those observed in nonsmokers.

Cigarette smoking is widely recognized for its harmful effects on respiratory, cardiovascular, and cerebrovascular health. Despite these well-documented risks, more than 30% of men of reproductive age continue to smoke 1 . Traditional cigarette smoking has been linked to a decrease in sperm count, reduced motility, and poor sperm morphology 2 . These effects are particularly severe in infertile men compared to the general population, with moderate to heavy smokers experiencing more significant reproductive challenges than those who smoke lightly 3 . According to the World Health Organization (WHO), the global prevalence of conventional cigarette smoking has been steadily declining, from 32.7% in 2000 to a projected 20.4% by 2025 4 . Contrary to the declining trend in traditional cigarette use, electronic cigarettes (E-cigarettes) are gaining popularity. E-cigarettes are devices that heat a liquid containing nicotine and other chemicals to create a vapor for inhalation. While the first generation of E-cigarettes was disposable, the current fourth generation offers reusable, rechargeable, and refillable devices, enabling users to customize their liquid compositions 5 . Because E-cigarettes do not contain major harmful components found in traditional cigarettes, such as tar and carbon monoxide, they are often perceived as a safer alternative or a stepping stone toward quitting smoking 6 , 7 . Aggressive marketing by the E-cigarette industry has further fueled their increasing popularity. Despite their growing use, comprehensive global data on E-cigarette usage rates are not yet available. Since 2013, several countries have begun to collect national data on E-cigarette use, and currently, 55 countries have such data available 1 . The appealing flavors, perceived lower harm, and trendy image of E-cigarettes are attracting nonsmokers and young adolescents 5 , with studies showing that 40% of E-cigarette users have no prior experience with conventional smoking 8 . E-cigarette liquids primarily consist of glycol and nicotine, but they also contain over 80 other chemicals in both the liquid and vapor forms. Glycol, typically found in forms such as propylene glycol and glycerol, is generally considered nontoxic. However, it can generate harmful substances when it undergoes oxidation and decomposition due to heating. Nicotine levels in E-cigarette vapor can range from zero to 35 mg per inhalation. Other components include nanoparticles and metals such as lead, cadmium, chromium, tin, silver, nickel, aluminum, and mercury 5 , 9 . While these substances have been reported to negatively impact respiratory, autoimmune, and liver functions 9 – 11 , their effects on human reproductive health have not been well-studied. There is also a significant gap in research regarding the impact of E-cigarettes on outcomes in assisted reproductive technology (ART). This study aims to address this gap by comparing the effects of conventional cigarette use and E-cigarette use on the reproductive outcomes of male partners in couples undergoing in vitro fertilization (IVF).