Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome
Abstract
1. Introduction
2. Methodology
3. Vitamin D Structure and Metabolism
4. Vitamin D Deficiency
5. Correlation Between Vitamin D and Ovarian Reserve, Steroidogenesis, and Follicular Development
6. Vitamin D Receptor in Reproductive-Associated Tissues
7. Vitamin D and Fertility
8. Vitamin D and PCOS
Study | Country | Total Participants (N) | Cases (n) | Controls (n) | Age | BMI | Baseline 25(OH)D | Type of Study | Conclusions |
---|---|---|---|---|---|---|---|---|---|
Trummer et al. (2019) [100] | Austria | N = 123 | n = 81 | n = 42 | 25.9 ± 4.7 years | 27.5 ± 7.3 kg/m2 | 48.8 ± 16.9 ng/mL | Randomized controlled trial | VD supplementation resulted in a reduction in plasma glucose after 60 min during the OGTT. Aside from this, it had no significant effect on metabolic and endocrine parameters in PCOS. |
Ostadmohammadi et al. (2019) [105] | Iran | N = 60 | n = 30 | n = 30 | 24.9 ± 4.9 years | 24.7 ± 4.6 kg/m2 | - | Randomize, double-blind, placebo-controlled clinical trial | Supplementation of VD and probiotics, when compared to placebo, significantly improved depression, anxiety, stress, general health, and overall well-being in women with PCOS. It also contributed to a decrease in total testosterone, hirsutism, inflammation, and oxidative stress. Furthermore, there was a notable increase in total antioxidant capacity and glutathione levels. |
Lerchbaum et al. (2021) [102] | Austria | N = 330 | n = 180 | n = 150 | 30.5 ± 6.9 years | 26.5 ± 6.7 kg/m2 | 50.4 ± 19.0 ng/mL | Double-blind randomized controlled trial | VD treatment in women with PCOS significantly affected FSH and the LH/FSH ratio after 24 weeks, but did not impact AMH levels. No significant effects were observed in non-PCOS women. |
Dastorani et al. (2018) [106] | Iran | N = 40 | n = 20 | n = 20 | 30.0 ± 3.93 years | 28.05 ± 3.31 kg/m2 | 10.75 ± 2.45 ng/mL | Randomize, double-blind, placebo-controlled trial | VD supplementation significantly reduced serum AMH, insulin levels, and insulin resistance (HOMA-IR) while increasing insulin sensitivity (QUICKI) compared to the placebo. Additionally, it led to a significant decrease in total cholesterol and LDL cholesterol levels. |
Javed et al. (2019) [107] | United Kingdom | N = 37 | n = 18 | n = 19 | 28.6 ± 6.4 years | 34.58 ± 9.01 kg/m2 | 28.32 ± 11.25 ng/mL | Randomized, double-blind, placebo-controlled study | This study shows that VD supplementation has beneficial effects on liver injury and fibrosis markers (ALT levels), along with modest improvements in insulin resistance (HOMA-IR) in overweight and obese VD-deficient women with PCOS. However, no significant changes were seen in other cardiovascular risk factors or hormones. |
Azhar et al. (2024) [108] | Pakistan | N = 180 | n = 120 | n = 60 | 33.2 ± 6.7 years | 28.1 ± 5.7 kg/m2 | - | Comparative descriptive study | Women with PCOS had lower VD levels. Both women with PCOS and VD deficiency exhibited lower HDL levels and higher total cholesterol, LDL, VLDL, and triglyceride levels compared to women without PCOS or those with sufficient or insufficient VD levels. |
Irani et al. (2015) [109] | United States | N= 53 | n = 35 | n = 18 | 30.2 ± 1.3 years | 29.3 ± 1.6 kg/m2 | - | Randomized placebo-controlled trial | VD supplementation in women with PCOS increased VD levels and led to shorter menstrual cycles, reduced hirsutism (Ferriman–Gallwey score), lower triglycerides, and a decreased TGF-β1-to-sENG ratio, highlighting VD’s potential role in improving lipid metabolism and inflammation in PCOS. |
Wen et al. (2024) [110] | China | N = 57 | n = 28 | n = 29 | 26.0 ± 8.9 years | 25.0 ± 7.6 kg/m2 | 12.7 ± 4.7 ng/mL | Randomized controlled trial | VD supplementation increased serum 25(OH)D levels. After 12 weeks, women in the VD group had lower BMI, WHR, insulin, HOMA-IR, triglycerides, total cholesterol, and LDL-C compared to the control group in women with obesity or insulin resistance. |
Krul-Poel et al. (2018) [111] | Netherlands | N = 1088 | n = 639 | n = 449 | 33.2 ± 5.1 years | 24.7 ± 5.4 kg/m2 | 55.4 ± 35.5 ng/mL | Cross-sectional comparison study | VD deficiency in PCOS may contribute to metabolic issues, especially insulin resistance and lipid abnormalities. Women with PCOS had lower VD levels, which were associated with higher insulin resistance (HOMA-IR) and poorer lipid profiles, including reduced HDL-cholesterol and apolipoprotein A1. |
9. Vitamin D and Endometriosis
10. Discussion
11. Conclusions
Funding
Conflicts of Interest
References
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Study | Country | Total Participants (N) | Cases (n) | Controls (n) | Age | BMI | Baseline 25(OH)D | Type of Study | Conclusions |
---|---|---|---|---|---|---|---|---|---|
Aflatoonian et al. (2014) [84] | Iran | N = 114 | n = 57 | n = 57 | 29.0 ± 4.3 years | 26.58 ± 1.72 kg/m2 | 15.02 ± 6.14 ng/mL | Randomized clinical trial | VD insufficiency treatment did not significantly improve pregnancy rates in frozen-thawed embryo transfer cycles. |
Bezerra Espinola et al. (2020) [85] | Italy | N = 100 | n = 50 | n = 50 | 35.30 ± 5.41 years | 21.95 ± 2.20 kg/m2 | 23.40 ± 6.65 ng/mL | Prospective randomized controlled pilot study | Vitamin D3 supplementation (2000 IU/day) improved implantation rates in IVF patients (37.1% vs. 19.2%, p = 0.0151), particularly in those with baseline VD ≥ 20 ng/mL. No significant difference in ongoing pregnancy or miscarriage rates. |
Doryanizadeh et al. (2020) [86] | Iran | N = 95 | n = 51 | n = 44 | 32.08 ± 4.90 years | 25.11 ± 3.29 kg/m2 | 27.55 ± 1.80 ng/mL | Double-blind randomized clinical trial | Calcitriol significantly increased chemical pregnancy rates (31.4% vs. 18.2%, p < 0.05), but had no significant effect on clinical pregnancy (25.5% vs. 13.6%) or ongoing pregnancy at 20 weeks (9.8% vs. 11.6%). |
Somigliana et al. (2021) [87] | Italy | N = 630 | n = 308 | n = 322 | 35.0 ± 3.9 years | 21.5 ± 2.3 kg/m2 | 20.0 ± 5.1 ng/mL | Double-blind randomized controlled trial | A single high dose (600,000 IU) of vitamin D3 before IVF did not improve clinical pregnancy rates (37% vs. 40%, p = 0.37) or IVF outcomes. No specific subgroup benefited from supplementation. Further studies are needed. |
Anifandis et al. (2010) [88] | Greece | N = 101 | n = 21 | n = 80 | 36.16 ± 5.29 years | 24.10 ± 2.99 kg/m2 | 23.37 ± 8.45 ng/mL | Prospective observational study | Higher follicular fluid VD levels (>30 ng/mL) were associated with lower embryo quality and reduced pregnancy rates (14.3% vs. 32.3–32.7%, p = 0.047). Increased VD levels correlated with lower follicular fluid glucose levels, possibly affecting oocyte quality and IVF outcomes. |
Franasiak et al. (2015) [89] | United States | N = 517 | n = 208 | n = 309 | 35.25 ± 4.27 years | 25.04 ± 5.42 kg/m2 | 24.20 ± 4.65 ng/mL | Retrospective cohort study | Vitamin D levels were not associated with IVF success after euploid blastocyst transfer. No significant differences in implantation or pregnancy rates across VD categories. Measuring VD does not predict implantation likelihood in this population. |
Fabris et al. (2014) [90] | Spain | N = 267 | n = 41 | n = 226 | 40.78 ± 0.76 years | 22.89 ± 0.76 kg/m2 | >30 ng/mL | Retrospective cohort study | VD levels did not correlate with pregnancy rates in egg donation recipients. No significant differences in implantation (61% vs. 63.4% vs. 65.2%), pregnancy (70% vs. 69.9% vs. 73.9%), or ongoing pregnancy rates (55.9% vs. 52.7% vs. 60.7%). No evidence to recommend VD screening in egg donation patients. |
Abedi et al. (2019) [72] | Iran | N = 85 | n = 42 | n = 43 | 31.34 ± 4.30 years | 23.85 ± 2.00 kg/m2 | 13.54 ± 6.50 ng/mL | Randomized double-blind placebo-controlled trial | VD supplementation (50,000 IU weekly for 6 weeks before ICSI) significantly improved endometrial quality (81% vs. 55.8%, p = 0.015), chemical pregnancy rate (47.6% vs. 25.5%, p = 0.013), and clinical pregnancy rate (38.1% vs. 20.9%, p = 0.019). No significant effect on oocyte retrieval, fertilization rate, or embryo quality. |
Study | Country | Total Participants (N) | Cases (n) | Controls (n) | Age | BMI | Baseline 25(OH)D | Type of Study | Conclusions |
---|---|---|---|---|---|---|---|---|---|
Chamgordani et al. (2024) [127] | Iran | N = 59 | n= 29 | n= 30 | 36.5 ± 5.5 years | 26.4 ± 3.9 kg/m2 | 27.3 ± 3.2 ng/mL | Case Control Study | Women with advanced endometriosis had higher NK cell percentages than controls, but no significant correlation was found between NK cells and vitamin D levels. Serum vitamin D levels were slightly higher in endometriosis cases, but the difference was not significant (p = 0.12). |
Somigliana E et al. (2007) [82] | Italy | N = 140 | n = 87 | n = 53 | 33.7 ± 6.0 years | 21.9 ± 3.4 | 24.9 ± 14.8 ng/mL | Prospective cohort study | Women with endometriosis had higher serum levels of 25-hydroxyvitamin D3. A positive gradient was observed according to disease severity. |
Miyashita M et al. (2016) [128] | Japan | N = 76 | n = 39 | n = 37 | 34.3 ± 1.4 years | - | 20.2 ± 1.3 ng/mL | Case–control study with in vitro experiments | Lower serum 25(OH)D3 levels were found in patients with severe endometriosis. VD suppressed inflammatory markers and reduced ESC proliferation, suggesting a potential therapeutic role. |
Nodler et al. (2020) [7] | United States | N = 149 | n = 47 | n = 22 | 19.67 ± 3.1 years | 26.07 ± 5.46 kg/m2 | 35.3 ± 13.9 ng/mL | Randomize, double-blind, placebo-controlled clinical trial | In young women with endometriosis, neither VD nor fish oil significantly reduced pain compared to placebo. The improvement observed in the placebo group highlights the need for further research to understand this effect. |
Zheng et al. (2023) [126] | Chinese | N = 589 | n = 315 | n = 274 | 31.47 ± 4.24 years | - | - | Randomized controlled trial | A randomized controlled trial showed that supplementation with antioxidant vitamins, including VD, significantly reduced dysmenorrhea, dyspareunia, and chronic pelvic pain in women with endometriosis. It also improved the overall quality of life. |
Mehdizadehkashi et al. (2021) [129] | Iran | N = 60 | n = 30 | n = 30 | 35.2 ± 7.05 years | 24.7 ± 3.5 kg/m2 | - | Randomize, double-blind, placebo-controlled clinical trial | A 12-week supplementation with VD improved pelvic pain, cholesterol ratio, hs-CRP, and TAC levels in endometriosis patients but did not affect other symptoms. Findings on VD-binding protein were inconsistent. Further research is needed to fully understand its effects on endometriosis. |
Harris et al. (2013) [130] | United States | N = 70,556 | n = 1385 | n = 69,171 | 35.92 ± 4.25 years | - | - | Prospective cohort study | This cohort showed that plasma 25(OH)D levels were inversely associated with endometriosis. Women with the highest levels of VD had a 24% lower risk of endometriosis than women with the lowest levels. |
Xie et al. (2024) [131] | Germany | N = 3232 | n = 257 | n = 2975 | 38.43 ± 9.57 years | 27.32 ± 4.5 kg/m2 | 21.36 ± 10.01 ng/mL | Observational cross-sectional study | Findings were that higher serum 25(OH)D concentrations were associated with a decreased incidence of endometriosis, with data suggesting that adequate sun exposure may lower risk for VD deficiency. |
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van Tienhoven, X.A.; Ruiz de Chávez Gascón, J.; Cano-Herrera, G.; Sarkis Nehme, J.A.; Souroujon Torun, A.A.; Bautista Gonzalez, M.F.; Esparza Salazar, F.; Sierra Brozon, A.; Rivera Rosas, E.G.; Carbajal Ocampo, D.; et al. Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome. Int. J. Mol. Sci. 2025, 26, 2256. https://doi.org/10.3390/ijms26052256
van Tienhoven XA, Ruiz de Chávez Gascón J, Cano-Herrera G, Sarkis Nehme JA, Souroujon Torun AA, Bautista Gonzalez MF, Esparza Salazar F, Sierra Brozon A, Rivera Rosas EG, Carbajal Ocampo D, et al. Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome. International Journal of Molecular Sciences. 2025; 26(5):2256. https://doi.org/10.3390/ijms26052256
Chicago/Turabian Stylevan Tienhoven, Ximena A., Jimena Ruiz de Chávez Gascón, Gabriela Cano-Herrera, José Antonio Sarkis Nehme, Ariela A. Souroujon Torun, Maria Fernanda Bautista Gonzalez, Felipe Esparza Salazar, Ana Sierra Brozon, Eder Gabriel Rivera Rosas, Dante Carbajal Ocampo, and et al. 2025. "Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome" International Journal of Molecular Sciences 26, no. 5: 2256. https://doi.org/10.3390/ijms26052256
APA Stylevan Tienhoven, X. A., Ruiz de Chávez Gascón, J., Cano-Herrera, G., Sarkis Nehme, J. A., Souroujon Torun, A. A., Bautista Gonzalez, M. F., Esparza Salazar, F., Sierra Brozon, A., Rivera Rosas, E. G., Carbajal Ocampo, D., & Cabrera Carranco, R. (2025). Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome. International Journal of Molecular Sciences, 26(5), 2256. https://doi.org/10.3390/ijms26052256