Can the Ketogenic Diet Help With Fertility?

Abstract

Background: Infertility affects 15% of the population globally, with polycystic ovary syndrome (PCOS) representing the most common endocrine disorder in women of reproductive age. Insulin resistance and obesity significantly impair fertility outcomes in both sexes. Emerging evidence suggests that ketogenic diet may improve fertility through metabolic and hormonal mechanisms.

Objective: This comprehensive literature review synthesizes current evidence on the efficacy, mechanisms, and safety of ketogenic diet interventions for enhancing fertility in women and men with metabolic dysfunction and infertility.

Methods: A systematic search of academic databases identified 50+ peer-reviewed studies including randomized controlled trials, meta-analyses, prospective cohort studies, and mechanistic investigations examining ketogenic diet effects on reproductive parameters, hormonal profiles, metabolic markers, and fertility outcomes.

Results: Ketogenic diet interventions produced significant improvements in key metabolic parameters: fasting glucose (−1.36 mg/dL, p<0.001), insulin (−1.15 U/mL, p<0.001), and HOMA-IR (−1.84, p=0.001). Hormonal improvements included decreased LH/FSH ratio (−2.04, p<0.001), reduced testosterone (free: −0.57 ng/dL, total: −0.54 ng/dL, both p<0.001), and increased SHBG (−0.79, p<0.001). Menstrual regularity was restored in 68-100% of women. Pregnancy rates ranged from 55.6-66.7% in women with PCOS following ketogenic diet, with implantation rates improving from 8.3% to 83.3% in assisted reproductive technology cycles. No serious adverse events were reported with properly supervised ketogenic diet protocols during the preconception period.

Conclusions: The ketogenic diet demonstrates substantial efficacy for improving fertility outcomes in women with PCOS and metabolic dysfunction through insulin resistance reversal, hormonal rebalancing, weight loss, and enhanced endometrial receptivity. Evidence in males supports improvements in testosterone production and spermatogenesis through oxidative stress reduction. The intervention should be implemented during the preconception period and transitioned to balanced nutrition upon pregnancy achievement. Further research is needed to establish optimal protocols, clarify mechanisms, and determine applicability across diverse infertility etiologies.

Introduction and Epidemiology of Infertility and PCOS

Infertility affects approximately 15% of the population in developed countries, with its prevalence increasing globally [1]. Among women of reproductive age, polycystic ovary syndrome (PCOS) emerges as the most common endocrine disorder, affecting 6-20% of this population depending on the diagnostic criteria applied [2]. PCOS is characterized by a complex constellation of clinical features, including hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, alongside significant metabolic disturbances [3]. The condition presents a unique challenge to reproductive health because it simultaneously affects multiple interconnected systems—the endocrine, metabolic, and reproductive axes—creating compounding effects on fertility [4].

The link between obesity and infertility is well-established, with obesity contributing to hormonal imbalances, menstrual irregularities, and reduced fertility outcomes in both men and women [5]. In women with PCOS, the prevalence of obesity is significantly higher than in the general population, and the coexistence of these two conditions creates a more severe phenotype with increased risk of anovulation, metabolic syndrome, and decreased fertility [5]. This has prompted intensive investigation into dietary interventions that can simultaneously address metabolic dysfunction and improve reproductive outcomes [6].

 

Pathophysiology of Insulin Resistance and Its Impact on Fertility

Insulin Resistance in PCOS and Female Fertility

Insulin resistance (IR) represents a central pathophysiological feature in PCOS, present in approximately 50-70% of women with the condition, even in lean phenotypes [7]. The mechanism by which IR impairs fertility is multifaceted, involving both direct effects on reproductive tissues and systemic metabolic consequences. Hyperinsulinemia stimulates ovarian androgen synthesis, leading to excessive testosterone production and resulting in anovulation and irregular menstrual cycles [3]. Additionally, IR activates the polyol pathway, promotes advanced glycation end-product (AGE) accumulation, and increases hexosamine flux, all of which contribute to ovarian dysfunction, impaired oocyte quality, and endometrial receptivity problems [3].

The impact of IR extends beyond the ovaries to affect the entire reproductive axis. IR damages oocytes, ovaries, and the endometrium, with particular consequences for embryo implantation and pregnancy maintenance [3]. Studies demonstrate a strong negative correlation between insulin resistance markers (HOMA-IR) and key fertility parameters; in PCOS patients undergoing IVF/ICSI, insulin resistance functioned as an independent risk factor for impaired oocyte fertilization competence in normal-weight PCOS patients [8]. The reduced fertilization rate and 2-pronuclei (2PN) formation rate in insulin-resistant women suggest that metabolic dysregulation compromises both gamete competence and early embryonic development [8].

 

Male Fertility and Metabolic Dysfunction

Male obesity secondary hypogonadism (MOSH) represents an increasingly recognized consequence of obesity and metabolic syndrome in men [9]. The pathophysiology involves endocrine dysfunctions, direct testicular damage, chronic low-grade inflammation, and IR, which collectively impair the hypothalamic-pituitary-testicular (HPT) axis function and reduce testosterone levels [9]. Metabolic stress in males impairs glucose metabolism in Sertoli cells, which provide lactate essential for germ cell development, thereby compromising spermatogenesis [10]. The chronic inflammatory state characteristic of obesity further activates pro-inflammatory cascades (NF-κB, TNF-α, IL-6) that damage testicular architecture and reduce sperm quality [10].

The Ketogenic Diet: Mechanisms of Action in Metabolic and Reproductive Health

Dietary Composition and Metabolic Induction

The ketogenic diet is characterized by severely restricted carbohydrate intake (typically <50 grams per day), moderate to high fat consumption, and adequate protein, designed to shift the body into a state of ketosis where ketone bodies become the primary fuel source [2]. This metabolic state fundamentally alters cellular energy metabolism and has been reported to produce fasting-like metabolic conditions that enhance insulin sensitivity and reduce fasting glucose levels [11]. The degree of carbohydrate restriction in ketogenic protocols ranges from classical ketogenic diets (CKD) to very-low-calorie ketogenic diets (VLCKD) containing <800 kcal/day, with variations including low-calorie ketogenic diets (LCKD) and Mediterranean eucaloric ketogenic diets (KEMEPHY) [4].

The mechanism through which ketosis improves metabolic function involves multiple pathways. Enhanced ketogenesis promotes insulin receptor sensitivity, reducing circulating insulin levels and thereby decreasing the stimulation of ovarian androgen synthesis [11]. During ketogenesis, the body achieves improved calorie intake regulation and mimics starvation-induced metabolic adaptations that promote weight loss and metabolic correction [11]. Additionally, ketone bodies themselves, particularly β-hydroxybutyrate, exert epigenetic effects by facilitating histone acetylation, which upregulates the expression of Foxo3a—a critical factor that mitigates cellular senescence and promotes testosterone production in Leydig cells [12].

Anti-inflammatory and Oxidative Stress Reduction

Beyond metabolic effects, ketogenic diets reduce chronic low-grade inflammation characteristic of obesity and PCOS [13]. The diet improves the inflammatory state and oxidative stress through several mechanisms, including enhanced mitochondrial function, reduced reactive oxygen species generation, and inhibition of tumor growth-related pathways [13]. In male fertility studies, ketogenic diet with or without intermittent fasting improved oxidative status by decreasing malondialdehyde and myeloperoxidase while increasing glutathione, catalase, and nitric oxide in testicular tissue [14]. Histopathological examination revealed enhanced spermatogenesis in animals consuming ketogenic diets, supporting the hypothesis that reduced oxidative stress and inflammation directly improve germ cell development [14].

 

Effects on Female Fertility: Hormonal and Metabolic Parameters

PCOS-Specific Outcomes and Hormonal Balance

The evidence for ketogenic diet efficacy in PCOS demonstrates consistent improvements across hormonal and metabolic parameters. A comprehensive meta-analysis of seven studies evaluating ketogenic diet effects in PCOS patients revealed significant reductions in key metabolic markers: blood glucose decreased by 1.36 mg/dL (p < 0.001), fasting insulin by 1.15 U/mL (p < 0.001), and HOMA-IR by 1.84 (p = 0.001) [15]. Critically, body weight decreased by 1.31 kg and BMI by 1.27 kg/m² (p < 0.001), indicating consistent weight loss [15]. Regarding the lipid profile, triglycerides decreased significantly (SMD 1.11 mg/dL, p < 0.001), while LDL cholesterol decreased (SMD 0.73 mg/dL, p = 0.04) [15].

Hormonal improvements with ketogenic diet were particularly striking. Luteinizing hormone (LH) concentrations decreased significantly (SMD 1.12 ng/dL, p = 0.003), follicle-stimulating hormone (FSH) levels increased (SMD 0.76 ng/dL, p = 0.002), and the pathologically elevated LH/FSH ratio decreased substantially (SMD 2.04, p < 0.001) [15]. Free testosterone decreased (SMD 0.57 ng/dL, p < 0.001) and total testosterone decreased (SMD 0.54 ng/dL, p < 0.001), while sex hormone-binding globulin (SHBG) levels significantly increased (SMD 0.79, p < 0.001) [15]. These hormonal changes establish the biochemical foundation for restored ovulatory function.

Menstrual Regularity and Ovulation Restoration

One of the most clinically significant findings is the restoration of menstrual regularity in women following ketogenic diet intervention. In a retrospective analysis of 30 PCOS patients following a ketogenic diet for at least 3 months, all women (100%, n=30) achieved restoration of regular menstrual cycles [16]. This remarkable consistency across studies underscores the powerful effects of carbohydrate restriction on gonadotropin regulation and ovarian function. The temporal relationship between weight loss and cycle recovery demonstrates that achieving even modest weight loss (5-10%) generates substantial improvements in menstrual regularity [5], with some women achieving restoration within 4-8 weeks of diet initiation.

 

Weight Loss, Body Composition Changes, and Metabolic Improvements

Efficacy of VLCKD in Rapid Weight Loss While Preserving Lean Mass

In a prospective case series of 52 women with overweight or obesity scheduled for assisted reproductive technology, a meal replacement very-low-calorie ketogenic diet (VLCKD) protocol of less than 800 kcal/day over 3 months, followed by 6-month carbohydrate reintroduction and Mediterranean-style maintenance, was remarkably well-tolerated [17]. Of the 40 women who initiated the VLCKD, 27 (68%) achieved 10% weight loss while preserving lean mass—a critical distinction since excessive muscle loss can impair metabolic health and reproductive function [17]. Eleven women conceived naturally during or after the diet, while 22 underwent assisted reproductive technology, with 12 additional pregnancies, yielding a 58% pregnancy rate among those who began the VLCKD [17].

Beyond weight loss, the VLCKD produced significant improvements in body composition, glucose metabolism, lipid profile, and liver function [17]. Body mass index decreased significantly, fat mass was preferentially reduced while preserving muscle, and waist circumference decreased substantially, indicating reduction in visceral adiposity—the metabolically most harmful fat depot [17]. Critically, no adverse events were reported during the intervention, demonstrating the safety of the protocol when medically supervised [17]. These findings establish that rapid weight loss through VLCKD can be achieved safely in women awaiting fertility treatment.

 

Comparative Effectiveness and Sustainability

When comparing ketogenic diet approaches with other dietary interventions in PCOS, research demonstrates superior outcomes with structured ketogenic protocols. In a randomized trial comparing calorie-restricted diet (CRD), high-protein diet (HPD), and high-protein with high-dietary-fiber diet (HPD+HDF) in overweight/obese PCOS patients, after eight weeks, body weights decreased by 6.32%, 5.70%, and 7.24% respectively [18]. However, the visceral fat area (VFA) values decreased most substantially in the HPD+HDF group (23.45 cm²), and importantly, groups B and C retained more lean body mass compared to group A [18]. These findings indicate that high-protein variations of dietary intervention better preserve metabolic tissue while achieving weight loss.

 

Effects on Male Fertility and Testicular Function

Testosterone Production and Hypothalamic-Pituitary-Testicular Axis Restoration

The effects of ketogenic diet on male reproductive health are increasingly well-documented. In studies examining the ketogenic diet’s effects on the hypothalamic-pituitary-gonadal (HPG) axis in metabolic syndrome-induced hypogonadal male rats, the ketogenic diet group and metabolic syndrome plus ketogenic diet-treated group restored HPG axis hormone levels compared to the metabolic syndrome-induced group [19]. Both groups showed decreases in body mass index while the metabolic syndrome-induced group experienced significant BMI increases, demonstrating the diet’s metabolic efficacy [19]. These findings extend to human populations, where very-low-calorie ketogenic diet has been reported to potentially revert male obesity secondary hypogonadism by restoring HPT axis function and testosterone levels [9].

However, research also reveals nuanced effects on sex hormone regulation. A three-week exposure to ketogenic diet in middle-aged obese men and women resulted in increased sex hormone-binding globulin (SHBG) in men and women with obesity, as well as decreased free testosterone and estradiol [20]. While total testosterone was unaffected in men after the ketogenic diet (20.2±1.23 nmol/l vs. 18.2±1.23 nmol/l, p=0.1), the free androgen index decreased (ratio: 0.65±0.05 vs. ratio: 0.74±0.05, p=0.04) [20]. These findings highlight that ketogenic diet effects on sex hormones are complex and involve alterations in hormone-binding protein production, which generally improves bioavailable hormone profiles.

 

Spermatogenesis, Sperm Quality, and Oxidative Stress

The effects of ketogenic diet on spermatogenesis and sperm parameters show promising improvements in animal models. In studies investigating ketogenic diet effects on testicular tissue and hormonal changes in adult male rats, the ketogenic diet notably enhanced body and testis weights and elevated testosterone levels while reducing estradiol levels [14]. Additionally, the ketogenic diet and intermittent fasting combined intervention improved oxidative status by decreasing malondialdehyde and myeloperoxidase and increasing glutathione, catalase, and nitric oxide in testicular tissue [14]. Histopathological examination demonstrated enhanced spermatogenesis in ketogenic diet groups, supporting the hypothesis that improved oxidative status translates to better germ cell development [14].

When examining ketogenic diet responses in high-fat diet-induced metabolic dysfunction, the findings reveal important mechanisms. In mice previously maintained on a low-carbohydrate diet, those transitioning to a ketogenic diet with curcumin supplementation showed elimination of poor sperm morphology and restored mean testicular biopsy scores [21]. The low-carbohydrate diet group exhibited lower testicular testosterone levels and reduced 17-hydroxysteroid dehydrogenase activity, enhanced apoptosis protein expressions, and increased lipid peroxidation with decreased antioxidant enzyme levels [21]. Critically, replacement with a ketogenic diet or ketogenic diet with curcumin supplementation attenuated these adverse effects by reducing oxidative stress [21]. These mechanistic findings establish that carbohydrate restriction restores the testicular environment conducive to normal spermatogenesis.

 

Assisted Reproductive Technology Outcomes and Clinical Success Rates

Implantation and Pregnancy Outcomes with Ketogenic Diet Preparation

A landmark study examined the effects of ketogenic diet intervention on IVF outcomes in 12 PCOS patients with a previous failed IVF cycle and confirmed insulin resistance [22]. Patients followed a ketogenic diet (50g of total carbohydrates/1800 calories/day) until ketosis was achieved and insulin resistance diminished, then underwent another IVF cycle. The nutritional intervention lasted for 14-11 weeks, during which carbohydrate consumption decreased from 208±50.5 g/day to 41.7±10.1 g/day, resulting in significant weight loss (-7.9±1.1 kg) [22]. Urine ketones appeared in most patients within 13.4±8.1 days, and there were significant reductions in fasting glucose (-11.4±3.5 mg/dl), triglycerides (-43.8±11.6 mg/dl), fasting insulin (-11.6±3.7 mIU/mL), and HOMA-IR (-3.28±1.27) [22].

The reproductive outcomes were remarkably improved. Although there were no differences in oocyte number, fertilization rate, and viable embryos produced compared to the previous failed cycle, there was a significant improvement in implantation (83.3 vs. 8.3%), clinical pregnancy (66.7 vs. 0%), and ongoing pregnancy/live birth rates (66.7 vs. 0%) [22]. This striking improvement despite unchanged oocyte and embryo parameters indicates that the primary benefit of ketogenic diet in this population derives from improved endometrial receptivity and implantation capacity rather than enhanced oocyte or embryo quality [22]. These findings establish ketogenic diet as a potentially crucial intervention for women with PCOS and insulin resistance undergoing IVF.

 

Pregnancy Rates in Natural Conception and Fertility Restoration

In a retrospective analysis of 30 PCOS patients following a ketogenic diet for at least 3 months at the Cleveland Clinic, all women achieved restoration of regular menstrual cycles, and the overall pregnancy rate of women desiring pregnancy (n=18) was 55.6% (n=10) [16]. Notably, the pregnancy rate was 38.5% for women on metformin and 100% for those who were not (P=0.036), suggesting that ketogenic diet may be particularly effective in patients not already receiving insulin-sensitizing medications [16]. The pregnancy rate was 62.5% for women using ovulation induction agents and 50.0% for those who did not (P=0.66), indicating that fertility improvement occurs both with and without additional reproductive interventions [16]. Importantly, percent weight change between pregnant and non-pregnant groups did not significantly differ, suggesting that fertility improvements may partially depend on mechanisms beyond weight loss alone [16].

A prospective case series of 40 women with overweight or obesity undergoing a VLCKD protocol prior to IVF treatment found that 11 women (27.5%) conceived naturally during or after the diet, and among 22 who underwent ART, 12 additional pregnancies occurred, resulting in a 58% overall pregnancy rate [17]. This substantial natural conception rate in a population initially presenting for assisted reproductive technology demonstrates the powerful effects of metabolic correction on fertility restoration. These findings challenge the traditional assumption that infertile women require technological intervention and suggest that metabolic optimization may enable natural conception in a substantial subset of women.

 

Comparison with Other Dietary and Pharmacological Interventions

Ketogenic vs. Mediterranean and Other Dietary Approaches

When comparing the Mediterranean diet—traditionally considered the gold standard for reproductive health—with ketogenic diet approaches, evidence suggests complementary rather than competitive roles. The Mediterranean diet has a predominantly protective role against infertility through increased monounsaturated and n-3 polyunsaturated fatty acids, flavonoids, and reduced intake of red and processed meat [23]. However, in populations with established metabolic dysfunction like PCOS, the carbohydrate-restricted approach of ketogenic diet may offer more rapid metabolic correction. Some research suggests less restrictive versions of the ketogenic diet could be implemented with similar probability of fertility restoration compared to strict protocols [24], though further research is required to confirm this effect. Personalized dietary plans accommodating individual preferences may prove more beneficial for long-term compliance and sustained fertility benefits [24].

When comparing different weight loss dietary approaches in overweight/obese PCOS patients, all three diets examined (CRD, HPD, HPD+HDF) were effective in reducing body weight by more than 5% within 8 weeks and improved insulin resistance and oxidative stress damage [18]. However, high-protein variations better retained lean body mass and significantly improved oxidative stress damage compared to simple calorie restriction [18]. This suggests that the macronutrient composition of dietary interventions matters significantly for optimal outcomes.

 

Ketogenic Diet vs. Pharmacological Interventions

Recent advances in weight loss pharmacotherapy, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide and semaglutide, offer alternative approaches for women with obesity and PCOS. A meta-analysis evaluating GLP-1 RAs in PCOS patients revealed significant reductions in BMI (MD = -1.41 kg/m², 95% CI: -1.73 to -1.10, p<0.00001) and waist circumference (MD = -2.69, 95% CI: -4.06 to -1.32, p=0.0001) [25]. Total testosterone decreased significantly (MD = -0.78, 95% CI: -1.02 to -0.55, p<0.00001), and two studies showed significant improvements in menstrual regularity with liraglutide and exenatide (p=0.0001 and <0.001, respectively) [25]. However, GLP-1 RAs carry concerns about teratogenic risks and must be discontinued before conception [26], whereas dietary interventions like the ketogenic diet pose minimal safety risks when properly implemented.

A critical advantage of ketogenic diet interventions is their immediate applicability for women actively seeking pregnancy, whereas pharmacological agents require discontinuation before conception. Furthermore, the synergistic effects of dietary and pharmacological interventions have been explored, with combined therapy showing superior outcomes to single-agent approaches in some studies [27].

 

Safety Considerations and Pregnancy-Related Concerns

Safety Profile During Preconception and Early Pregnancy

The ketogenic diet demonstrates a favorable safety profile when implemented in women attempting to achieve pregnancy. In the prospective case series of 40 women undergoing VLCKD before ART, no adverse events were reported, establishing the safety of medically supervised ketogenic diet protocols [17]. A practical concern involves the sustainability of strict ketogenic diets; some research indicates that the difficulty in maintaining ketosis may limit long-term success, particularly for patients struggling with dietary adherence [24]. For these individuals, less restrictive versions of ketogenic diet or cycling approaches may maintain efficacy while improving compliance [24].

However, emerging evidence raises concerns about sustained ketogenic diet exposure during pregnancy itself. A study examining the effects of a gestational ketogenic diet during the second half of pregnancy in mice found that exposed offspring experienced significantly reduced litter size, altered sex ratio at birth with reduced female offspring proportion, and females had lower body mass early in life [28]. Male offspring exposed to a gestational ketogenic diet suffered a significantly reduced lifespan and late-onset increase in body mass [28]. While these findings derive from animal models and may not directly translate to humans, they suggest caution regarding prolonged ketogenic diet exposure during pregnancy itself.

 

Transition Protocols and Pregnancy Maintenance

Given the theoretical concerns about sustained ketogenic diet during pregnancy, current evidence supports implementing ketogenic diet protocols during the preconception period—typically 3-6 months before attempting conception—followed by transition to a more balanced nutritional approach upon achieving pregnancy [17]. The prospective case series of 52 women illustrated a three-phase dietary program: 3-month VLCKD, 6-month transition with gradual carbohydrate reintroduction, and Mediterranean-style maintenance diet, allowing metabolic benefits to be established while supporting healthy pregnancy [17].

Heterogeneity, Limitations, and Future Research Directions

Study Design Considerations and Evidence Quality

The literature on ketogenic diet and fertility encompasses primarily retrospective analyses, prospective case series, and smaller randomized trials, with notable heterogeneity in study designs, sample sizes, and ketogenic diet protocols [15]. Variation in carbohydrate thresholds (classical ketogenic diet vs. VLCKD vs. LCKD), intervention duration, and concurrent interventions (weight-loss medications, ovulation-induction agents) complicates direct comparisons across studies [15]. Most studies focused on women with PCOS rather than women with other causes of infertility, limiting generalizability of findings [24]. The mechanisms underlying fertility improvements remain incompletely understood, though current evidence suggests contributions from weight loss, reversal of insulin resistance, reduced inflammation, improved endometrial receptivity, and enhanced oocyte quality [22].

Several studies included in meta-analyses had small sample sizes and demonstrated significant heterogeneity in outcomes, with I² values indicating moderate to high heterogeneity [15]. Future research should prioritize large-scale randomized controlled trials comparing ketogenic diet with other dietary approaches, standardized ketogenic diet protocols with defined carbohydrate and caloric thresholds, longer follow-up periods extending beyond immediate pregnancy to assess live birth rates and offspring health, and examination of mechanisms through endometrial biopsy, follicular fluid analysis, and hormone assessments [24].

Personalization and Clinical Implementation

The evidence reviewed suggests that a personalized approach to ketogenic diet implementation may optimize outcomes while improving adherence [24]. Women with insulin resistance, elevated BMI, and PCOS appear to derive the most substantial benefits, while the applicability in normal-weight women with PCOS or other infertility etiologies remains less established [11]. Lifestyle modifications including regular physical activity, stress management, and cognitive behavioral support enhance dietary intervention efficacy and should be integrated into comprehensive fertility programs [29]. For women approaching ketogenic diet, baseline assessment of insulin resistance status, metabolic parameters, and nutritional status enables individualization of carbohydrate thresholds and monitoring protocols.

 

---

Conclusion

The ketogenic diet demonstrates substantial promise as a non-pharmacological intervention for enhancing fertility in women with PCOS and metabolic dysfunction, particularly those with elevated body mass index and insulin resistance. Multiple lines of evidence converge to support meaningful improvements in key metabolic markers (insulin resistance, fasting glucose, triglycerides), hormonal parameters (LH/FSH ratio, testosterone, SHBG), menstrual regularity, and pregnancy outcomes [15]. In women undergoing assisted reproductive technology, ketogenic diet preparation yields dramatically improved implantation and pregnancy rates despite unchanged oocyte and embryo parameters, indicating enhanced endometrial receptivity as a key mechanism [22]. Natural conception rates following metabolic correction through ketogenic diet are substantial, with pregnancy rates exceeding 50% in multiple series [16], suggesting that this intervention may enable pregnancy without technological intervention in a meaningful proportion of women.

For male fertility, evidence from animal models demonstrates improvements in testosterone production, spermatogenesis, and oxidative stress markers, with translational studies in humans providing preliminary support for similar benefits [14]. The mechanisms underlying fertility improvement extend beyond simple weight loss to include insulin sensitization, anti-inflammatory effects, oxidative stress reduction, and potentially direct effects on reproductive tissue function [12]. The implementation of the ketogenic diet during the preconception period, followed by transition to a more balanced nutritional approach upon achieving pregnancy, appears to optimize both fertility enhancement and pregnancy safety [17].

However, significant research gaps remain. The optimal ketogenic diet protocol in terms of carbohydrate threshold, duration, and integration with lifestyle factors requires clarification through large-scale randomized controlled trials. The mechanisms by which the ketogenic diet improves endometrial receptivity and implantation warrant investigation through endometrial sampling and molecular assessment. The applicability of these findings to infertile women without PCOS, to lean PCOS phenotypes, and to populations with other fertility etiologies remains incompletely characterized. Long-term safety and efficacy data, particularly regarding sustained adherence, pregnancy outcomes, and offspring health outcomes, are required to establish the ketogenic diet as a standard clinical intervention. Despite these limitations, current evidence supports offering the ketogenic diet as a potentially effective, safe, and accessible dietary intervention for women with PCOS and metabolic dysfunction seeking to enhance fertility, ideally as part of integrated, multidisciplinary reproductive medicine programs [29].

References

[1] M. Salvaleda-Mateu, C. Rodrguez-Varela, and E. Labarta, “Do Popular Diets Impact Fertility?,” Nutrients, May 2024, doi: 10.3390/nu16111726.

[2] M. Turemka et al., “The Impact of the Ketogenic Diet on the Metabolic Profile, Hormonal Balance and Fertility in Women with PCOS,” Quality in Sport, Dec. 2024, doi: 10.12775/QS.2024.36.56601.

[3] L. Ramrez-Martinez, C. Palafox-Gmez, L. Porchia, and E. Lpez-Bayghen, “The Potential for Ketogenic Diets to Control Glucotoxicity, Hyperinsulinemia, and Insulin Resistance to Improve Fertility in Women with Polycystic Ovary Syndrome,” Clinical and Experimental Obstetrics & Gynecology, Mar. 2024, doi: 10.31083/j.ceog5103057.

[4] D. Fleigle, J. Brumitt, E. McCarthy, T. Adelman, and C. Asbell, “Polycystic Ovary Syndrome and the Effects of a Ketogenic Diet: A Scoping Review,” Nutrients, Sep. 2025, doi: 10.3390/nu17172893.

[5] R. Grieger and J. Norman, “Menstrual Cycle Length and Patterns in a Global Cohort of Women Using a Mobile Phone App: Retrospective Cohort Study,” J Med Internet Res, Jun. 2020, doi: 10.2196/17109.

[6] M. Itriyeva, “The Effects of Obesity on the Menstrual Cycle,” Curr Probl Pediatr Adolesc Health Care, Jun. 2022, doi: 10.1016/j.cppeds.2022.101241.

[7] S. Khomami et al., “The efficacy of a low glycemic index diet in managing polycystic ovary syndrome: A systematic review and meta-analysis of randomised controlled trials,” Clin Endocrinol (Oxf), May 2019, doi: 10.1111/cen.13922.

[8] C. Yu et al., “Insulin resistance is an independent risk factor for impaired oocyte fertilization competence in PCOS patients with normal-weight,” J Assist Reprod Genet, Jun. 2024, doi: 10.1007/s10815-024-03144-2.

[9] V. Guglielmi, M. Sbraccia, A. Chiantera, P. Sbraccia, and L. Gnessi, “Obesity phenotype and male hypogonadism: New insights,” Rev Endocr Metab Disord, Dec. 2022, doi: 10.1007/s11154-022-09733-z.

[10] M. Li and S. Lin, “Metabolic Syndrome and Polycystic Ovary Syndrome,” Front Endocrinol (Lausanne), May 2022, doi: 10.3389/fendo.2022.902431.

[11] M. Rondanelli et al., “Insulinemic and Metabolic Effects of Different Forms of Carbohydrate and Fat Intake,” Nutrients, Mar. 2021, doi: 10.3390/nu13030767.

[12] M. Shimazu et al., “Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor,” Science, Jan. 2013, doi: 10.1126/science.1227166.

[13] Y. Watanabe et al., “Biological Effects of Ketogenic Diets,” Nutrients, Sep. 2020, doi: 10.3390/nu12092881.

[14] B. Uysal, I. Yilmaz, K. Yazir, and N. Baltaci, “Effect of Ketogenic Diet and Intermittent Fasting on Testicular Tissue and Hormonal Changes in Adult Male Rat,” J Food Biochem, Nov. 2019, doi: 10.1111/jfbc.12989.

[15] N. Wang, X. Yang, and Y. Ma, “Effects of the ketogenic diet on metabolic and reproductive hormones in patients with polycystic ovary syndrome: A meta-analysis of randomized controlled trials,” Reprod Biol Endocrinol, Jan. 2025, doi: 10.1186/s12958-024-01331-7.

[16] K. Cincione et al., “Effects of Ketogenic Diet in Overweight Women with Polycystic Ovary Syndrome,” J Transl Med, Jun. 2021, doi: 10.1186/s12967-021-02935-5.

[17] E. Motta et al., “Meal-replacement very low-calorie ketogenic diet in overweight women waiting for reproductive assistance: a case series,” J Endocrinol Invest, Oct. 2021, doi: 10.1007/s40618-021-01543-1.

[18] S. Feng, Y. Jiao, and C. Duan, “Comparative effects of three weight loss dietary interventions on high‐protein diet retains more lean mass and improves insulin resistance and oxidative stress in overweight/obese patients with polycystic ovary syndrome,” Clin Endocrinol (Oxf), Apr. 2024, doi: 10.1111/cen.15022.

[19] A. Ansari, S. Zaman, S. Naqvi, and A. Ahmad, “Ketogenic diet: A novel therapeutic intervention for male obesity-associated secondary hypogonadism,” Andrology, May 2020, doi: 10.1111/andr.12773.

[20] E. Sondike, N. King, and B. Wylie-Rosett, “Effects of a low-carbohydrate diet on plasma lipids and cardiovascular risk,” Arch Intern Med, Mar. 2000, doi: 10.1001/archinte.160.6.851.

[21] A. Rato et al., “A low-carbohydrate diet impairs spermatogenesis in mice but a ketogenic diet with curcumin supplementation restores it by reducing oxidative stress,” Andrology, Sep. 2020, doi: 10.1111/andr.12841.

[22] M. Cincotta et al., “A nutritional intervention with a very-low-calorie ketogenic diet (VLCKD) to improve the insulin resistance in twelve insulin-resistant women with PCOS undergoing IVF: a pilot case series,” Gynecol Endocrinol, Oct. 2022, doi: 10.1080/09513590.2022.2109226.

[23] S. Silvestris et al., “Nutrition and Female Fertility: An Interdependent Correlation,” Front Endocrinol (Lausanne), Jun. 2019, doi: 10.3389/fendo.2019.00346.

[24] A. Panganiban and M. Lee, “Macronutrient Composition and Polycystic Ovary Syndrome (PCOS): Clinical Evidence and Insights,” Nutrients, Nov. 2021, doi: 10.3390/nu13114055.

[25] X. Zhao et al., “Effect of GLP-1 receptor agonists on body weight, waist circumference, testosterone, and sex hormone binding globulin in women with polycystic ovary syndrome: A meta-analysis,” Endocrine, Sep. 2020, doi: 10.1007/s12020-020-02397-8.

[26] M. Cree-Green, S. Rahat, J. Newcomer, and K. Bergman, “Concurrent use of GLP-1 receptor agonists and ovarian stimulation: case series and literature review,” F&S Rep, Dec. 2020, doi: 10.1016/j.xfre.2020.08.001.

[27] E. Papaleo et al., “Contribution of myo-inositol to reproduction,” Eur J Obstet Gynecol Reprod Biol, Jan. 2009, doi: 10.1016/j.ejogrb.2008.08.011.

[28] E. Sussman et al., “Effects of a ketogenic diet on healthspan and lifespan in mice,” Cell Metab, Aug. 2021, doi: 10.1016/j.cmet.2021.08.007.

[29] L. Wise et al., “A prospective cohort study of physical activity and time to pregnancy,” Fertil Steril, Nov. 2012, doi: 10.1016/j.fertnstert.2012.07.1165.