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Low vitamin D levels in follicular fluid, but not in serum, are associated with adverse outcomes in assisted reproduction

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
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Abstract

Purpose

To assess the relationship between serum/follicular fluid (FF) vitamin D (VD) status and assisted reproductive technology (ART) treatment outcomes among infertile patients.

Methods

A prospective cohort study, including 132 infertile patients scheduled for their first ART treatment cycle, was carried out in a Reproductive Medical Center. Serum and FF samples were collected to assess 25-hydroxy VD [25(OH)D] levels. Low VD level was defined as 25(OH)D concentration of less than 30 ng/mL.

Results

Most infertile patients had low VD levels in serum (88%) and FF (90%). We observed a moderately positive correlation between VD levels in serum and FF (r = 0.34, p < 0.0001). Compared to the group of patients with low VD levels in the FF, those with sufficient VD levels had a significantly higher number of retrieved oocytes (p = 0.03), normal fertilization (p = 0.01), and high-quality embryos (p = 0.001). Moreover, patients with sufficient VD levels in the FF also had significantly higher implantation rates than those with low VD levels (76.92% vs. 46.58%, respectively, p = 0.01) and clinical pregnancy rates (92.31% vs. 61.54%, respectively, p = 0.04).

Conclusion

These data collectively revealed that low VD levels in serum and FF were common among infertile patients. VD levels in FF, but not in serum, were associated with embryo quality, normal fertilization, implantation rates, and clinical pregnancy rates. Further studies are mandatory to determine the molecular mechanism and VD’s potential therapeutic benefits in infertile patients.

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Availability of data and material

All datasets generated for this study are included in the article.

References

  1. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408. https://doi.org/10.1152/physrev.00014.2015

    Article  CAS  PubMed  Google Scholar 

  2. Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L (2012) Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol 280(1):36–43. https://doi.org/10.1016/j.cellimm.2012.10.009

    Article  CAS  PubMed  Google Scholar 

  3. Van Etten E, Decallonne B, Verlinden L, Verstuyf A, Bouillon R, Mathieu C (2003) Analogs of 1alpha,25-dihydroxyvitamin D3 as pluripotent immunomodulators. J Cell Biochem 88(2):223–226. https://doi.org/10.1002/jcb.10329

    Article  CAS  PubMed  Google Scholar 

  4. Irani M, Merhi Z (2014) Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril 102(2):460–8 e3. https://doi.org/10.1016/j.fertnstert.2014.04.046

    Article  CAS  PubMed  Google Scholar 

  5. Du H, Daftary GS, Lalwani SI, Taylor HS (2005) Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol 19(9):2222–2233. https://doi.org/10.1210/me.2004-0336

    Article  CAS  PubMed  Google Scholar 

  6. Wehr E, Pieber TR, Obermayer-Pietsch B (2011) Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest 34(10):757–763. https://doi.org/10.3275/7748

    Article  CAS  PubMed  Google Scholar 

  7. Asadi M, Matin N, Frootan M, Mohamadpour J, Qorbani M, Tanha FD (2014) Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial. Arch Gynecol Obstet 289(4):865–870. https://doi.org/10.1007/s00404-013-3055-x

    Article  CAS  PubMed  Google Scholar 

  8. Lasco A, Catalano A, Benvenga S (2012) Improvement of primary dysmenorrhea caused by a single oral dose of vitamin D: results of a randomized, double-blind, placebo-controlled study. Arch Intern Med 172(4):366–367. https://doi.org/10.1001/archinternmed.2011.715

    Article  PubMed  Google Scholar 

  9. Wise LA, Ruiz-Narvaez EA, Haddad SA, Rosenberg L, Palmer JR (2014) Polymorphisms in vitamin D-related genes and risk of uterine leiomyomata. Fertil Steril 102(2):503–10 e1. https://doi.org/10.1016/j.fertnstert.2014.04.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nair R, Maseeh A (2012) Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother 3(2):118–126. https://doi.org/10.4103/0976-500X.95506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281. https://doi.org/10.1056/NEJMra070553

    Article  CAS  PubMed  Google Scholar 

  12. Burgaz A, Orsini N, Larsson SC, Wolk A (2011) Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens 29(4):636–645. https://doi.org/10.1097/HJH.0b013e32834320f9

    Article  CAS  PubMed  Google Scholar 

  13. Satirapoj B, Limwannata P, Chaiprasert A, Supasyndh O, Choovichian P (2013) Vitamin D insufficiency and deficiency with stages of chronic kidney disease in an Asian population. BMC Nephrol 14:206. https://doi.org/10.1186/1471-2369-14-206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak-Kim J (2014) Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod 29(2):208–219. https://doi.org/10.1093/humrep/det424

    Article  CAS  PubMed  Google Scholar 

  15. Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA et al (2012) IOM committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab 97(4):1146–1152. https://doi.org/10.1210/jc.2011-2218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kebapcilar AG, Kulaksizoglu M, Kebapcilar L, Gonen MS, Unlu A, Topcu A et al (2013) Is there a link between premature ovarian failure and serum concentrations of vitamin D, zinc, and copper? Menopause 20(1):94–99. https://doi.org/10.1097/gme.0b013e31826015ca

    Article  PubMed  Google Scholar 

  17. Grundmann M, von Versen-Hoynck F (2011) Vitamin D—roles in women’s reproductive health? Reprod Biol Endocrinol 9:146. https://doi.org/10.1186/1477-7827-9-146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ranjana H (2017) Role of vitamin D in infertility. J Public Health Policy Plann. 1:8–10

  19. Human Fertilisation and Embryology Authority (HFEA). Fertility treatment in 2013: trends and figures. 2016. https://www.hfea.gov.uk/media/2081/hfea-fertility-trends-2013.pdf. Accessed 5 Jan 2020

  20. Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2015 Assisted Reproductive Technology National Summary Report. Atlanta (GA): US Dept of Health and Human Services; 2017. https://www.cdc.gov/art/pdf/2015-report/art-2015-national-summary-report.pdf. Accessed 28 Mar 2020

  21. Chu J, Gallos I, Tobias A, Tan B, Eapen A, Coomarasamy A (2018) Vitamin D and assisted reproductive treatment outcome: a systematic review and meta-analysis. Hum Reprod 33(1):65–80. https://doi.org/10.1093/humrep/dex326

    Article  PubMed  Google Scholar 

  22. Ciepiela P, Duleba AJ, Kowaleczko E, Chelstowski K, Kurzawa R (2018) Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome. J Assist Reprod Genet 35(7):1265–1276. https://doi.org/10.1007/s10815-018-1179-4

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hornstein MD (2019) Vitamin D and infertility: the evidence. Fertility Reprod 1(1):31–33

    Article  Google Scholar 

  24. Lv SS, Wang JY, Wang XQ, Wang Y, Xu Y (2016) Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet 293(6):1339–1345. https://doi.org/10.1007/s00404-016-4058-1

    Article  CAS  PubMed  Google Scholar 

  25. Albuquerque LE, Saconato H, Maciel MC (2005) Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles. Cochrane Database Syst Rev 1:CD002808. https://doi.org/10.1002/14651858.CD002808.pub2

    Article  Google Scholar 

  26. Xiao Y, Wang Y, Wang M, Liu K (2018) Follicular flushing increases the number of oocytes retrieved in poor ovarian responders undergoing in vitro fertilization: a retrospective cohort study. BMC Womens Health 18(1):186. https://doi.org/10.1186/s12905-018-0681-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brinsden PR (1999) A textbook of in vitro fertilization and assisted reproduction: the bourn hall guide to clinical and laboratory practice, 2nd edn. CRC Press, London

    Google Scholar 

  28. Liu X, Zhang W, Xu Y, Chu Y, Wang X, Li Q et al (2019) Effect of vitamin D status on normal fertilization rate following in vitro fertilization. Reprod Biol Endocrinol 17(1):59. https://doi.org/10.1186/s12958-019-0500-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Abuzeid MI, Bolonduro O, La Chance J, Abozaid T, Urich M, Ullah K et al (2014) Cumulative live birth rate and assisted reproduction: impact of female age and transfer day. Facts Views Vis Obgyn 6(3):145–149

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930. https://doi.org/10.1210/jc.2011-0385

    Article  CAS  PubMed  Google Scholar 

  31. Muyayalo KP, Huang XB, Qian Z, Li ZH, Mor G, Liao AH (2019) Low circulating levels of vitamin D may contribute to the occurrence of preeclampsia through deregulation of Treg /Th17 cell ratio. Am J Reprod Immunol 82(4):e13168. https://doi.org/10.1111/aji.13168

    Article  CAS  PubMed  Google Scholar 

  32. Chu J, Gallos I, Tobias A, Robinson L, Kirkman-Brown J, Dhillon-Smith R et al (2019) Vitamin D and assisted reproductive treatment outcome: a prospective cohort study. Reprod Health 16(1):106. https://doi.org/10.1186/s12978-019-0769-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Firouzabadi RD, Rahmani E, Rahsepar M, Firouzabadi MM (2014) Value of follicular fluid vitamin D in predicting the pregnancy rate in an IVF program. Arch Gynecol Obstet 289(1):201–206. https://doi.org/10.1007/s00404-013-2959-9

    Article  CAS  PubMed  Google Scholar 

  34. Boz I, Teskereci G, Ozekinci M (2020) High prevalence of vitamin D deficiency in Turkish women undergoing in vitro fertilization: a descriptive study. Health Care Women Int 41(2):147–158. https://doi.org/10.1080/07399332.2019.1569015

    Article  PubMed  Google Scholar 

  35. Xie Q-W, Zhang M (2013) White or tan? A cross-cultural analysis of skin beauty advertisements between China and the United States. Asian J Commun 23(5):538–554. https://doi.org/10.1080/01292986.2012.756046

    Article  Google Scholar 

  36. Zhang W, Stoecklin E, Eggersdorfer M (2013) A glimpse of vitamin D status in Mainland China. Nutrition 29(7–8):953–957. https://doi.org/10.1016/j.nut.2013.01.010

    Article  CAS  PubMed  Google Scholar 

  37. Aleyasin A, Hosseini MA, Mahdavi A, Safdarian L, Fallahi P, Mohajeri MR et al (2011) Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol 159(1):132–137. https://doi.org/10.1016/j.ejogrb.2011.07.006

    Article  CAS  PubMed  Google Scholar 

  38. Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C et al (2010) Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 94(4):1314–1319. https://doi.org/10.1016/j.fertnstert.2009.05.019

    Article  CAS  PubMed  Google Scholar 

  39. Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S et al (2010) Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol 8:91. https://doi.org/10.1186/1477-7827-8-91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mnallah S, Kacem Berjeb K, Braham M, Khrouf M, Chtourou S, Merdassi G et al (2017) Impact of vitamin D deficiency on ICSI outcomes. JFIV Reprod Med Genet. 5:201. https://doi.org/10.4172/2375-4508.1000201

    Article  Google Scholar 

  41. Fabris A, Pacheco A, Cruz M, Puente JM, Fatemi H, Garcia-Velasco JA (2014) Impact of circulating levels of total and bioavailable serum vitamin D on pregnancy rate in egg donation recipients. Fertil Steril 102(6):1608–1612. https://doi.org/10.1016/j.fertnstert.2014.08.030

    Article  CAS  PubMed  Google Scholar 

  42. Franasiak JM, Molinaro TA, Dubell EK, Scott KL, Ruiz AR, Forman EJ et al (2015) Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts. Am J Obstet Gynecol 212(3):315 e1-315 e6. https://doi.org/10.1016/j.ajog.2014.09.029

    Article  CAS  Google Scholar 

  43. Neville G, Martyn F, Kilbane M, O’Riordan M, Wingfield M, McKenna M et al (2016) Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection. Int J Gynaecol Obstet 135(2):172–176. https://doi.org/10.1016/j.ijgo.2016.04.018

    Article  CAS  PubMed  Google Scholar 

  44. Abadia L, Gaskins AJ, Chiu YH, Williams PL, Keller M, Wright DL et al (2016) Serum 25-hydroxyvitamin D concentrations and treatment outcomes of women undergoing assisted reproduction. Am J Clin Nutr 104(3):729–735. https://doi.org/10.3945/ajcn.115.126359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Merhi Z, Doswell A, Krebs K, Cipolla M (2014) Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells. J Clin Endocrinol Metab 99(6):E1137–E1145. https://doi.org/10.1210/jc.2013-4161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cunningham TK, Allgar V, Dargham SR, Kilpatrick E, Sathyapalan T, Maguiness S et al (2019) Association of vitamin D metabolites with embryo development and fertilization in women with and without PCOS undergoing subfertility treatment. Front Endocrinol (Lausanne) 10:13. https://doi.org/10.3389/fendo.2019.00013

    Article  Google Scholar 

  47. Farzadi L, Khayatzadeh Bidgoli H, Ghojazadeh M, Bahrami Z, Fattahi A, Latifi Z et al (2015) Correlation between follicular fluid 25-OH vitamin D and assisted reproductive outcomes. Iran J Reprod Med 13(6):361–366

    PubMed  PubMed Central  Google Scholar 

  48. Paffoni A, Ferrari S, Vigano P, Pagliardini L, Papaleo E, Candiani M et al (2014) Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab 99(11):E2372–E2376. https://doi.org/10.1210/jc.2014-1802

    Article  CAS  PubMed  Google Scholar 

  49. Garbedian K, Boggild M, Moody J, Liu KE (2013) Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. CMAJ Open 1(2):E77-82. https://doi.org/10.9778/cmajo.20120032

    Article  PubMed  PubMed Central  Google Scholar 

  50. Rudick BJ, Ingles SA, Chung K, Stanczyk FZ, Paulson RJ, Bendikson KA (2014) Influence of vitamin D levels on in vitro fertilization outcomes in donor-recipient cycles. Fertil Steril 101(2):447–452. https://doi.org/10.1016/j.fertnstert.2013.10.008

    Article  CAS  PubMed  Google Scholar 

  51. Jeppesen JV, Anderson RA, Kelsey TW, Christiansen SL, Kristensen SG, Jayaprakasan K et al (2013) Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 19(8):519–527. https://doi.org/10.1093/molehr/gat024

    Article  CAS  PubMed  Google Scholar 

  52. Arefi S, Khalili G, Iranmanesh H, Farifteh F, Hosseini A, Fatemi HM et al (2018) Is the ovarian reserve influenced by vitamin D deficiency and the dress code in an infertile Iranian population? J Ovarian Res 11(1):62. https://doi.org/10.1186/s13048-018-0435-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L (2001) Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 167(4):1945–1953. https://doi.org/10.4049/jimmunol.167.4.1945

    Article  CAS  PubMed  Google Scholar 

  54. Velthut A, Zilmer M, Zilmer K, Kaart T, Karro H, Salumets A (2013) Elevated blood plasma antioxidant status is favourable for achieving IVF/ICSI pregnancy. Reprod Biomed Online 26(4):345–352. https://doi.org/10.1016/j.rbmo.2012.12.012

    Article  CAS  PubMed  Google Scholar 

  55. Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37(4):277–285. https://doi.org/10.1016/j.clinbiochem.2003.11.015

    Article  CAS  PubMed  Google Scholar 

  56. Agarwal A, Gupta S, Sharma RK (2005) Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 3:28. https://doi.org/10.1186/1477-7827-3-28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Dalto DB, Matte JJ (2017) Pyridoxine (vitamin B(6)) and the glutathione peroxidase system; a link between one-carbon metabolism and antioxidation. Nutrients. https://doi.org/10.3390/nu9030189

    Article  PubMed  PubMed Central  Google Scholar 

  58. Nunez-Calonge R, Cortes S, Gutierrez Gonzalez LM, Kireev R, Vara E, Ortega L et al (2016) Oxidative stress in follicular fluid of young women with low response compared with fertile oocyte donors. Reprod Biomed Online 32(4):446–456. https://doi.org/10.1016/j.rbmo.2015.12.010

    Article  CAS  PubMed  Google Scholar 

  59. Olszak-Wąsik K, Bednarska-Czerwińska A, Olejek A, Tukiendorf A (2019) From, “every day” hormonal to oxidative stress biomarkers in blood and follicular fluid, to embryo quality and pregnancy success? Oxid Med Cell Longev 2019:1092415. https://doi.org/10.1155/2019/1092415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nagy RA, van Montfoort APA, Groen H, Homminga I, Andrei D, Mistry RH et al (2019) Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF. Sci Rep 9(1):12817. https://doi.org/10.1038/s41598-019-49091-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jain SK, Micinski D (2013) Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun 437(1):7–11. https://doi.org/10.1016/j.bbrc.2013.06.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tavakoli F, Namakin K, Zardast M (2016) Vitamin D supplementation and high-density lipoprotein cholesterol: a study in healthy school children. Iran J Pediatr 26(4):e3311. https://doi.org/10.5812/ijp.3311

    Article  PubMed  PubMed Central  Google Scholar 

  63. Ansari MGA, Sabico S, Clerici M, Khattak MNK, Wani K, Al-Musharaf S et al (2020) Vitamin D supplementation is associated with increased glutathione peroxidase-1 levels in arab adults with prediabetes. Antioxidants (Basel). https://doi.org/10.3390/antiox9020118

    Article  PubMed  PubMed Central  Google Scholar 

  64. Francis EC, Hinkle SN, Song Y, Rawal S, Donnelly SR, Zhu Y et al (2018) Longitudinal maternal vitamin D status during pregnancy is associated with neonatal anthropometric measures. Nutrients. https://doi.org/10.3390/nu10111631

    Article  PubMed  PubMed Central  Google Scholar 

  65. Leffelaar ER, Vrijkotte TG, van Eijsden M (2010) Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort. Br J Nutr 104(1):108–117. https://doi.org/10.1017/S000711451000022X

    Article  CAS  PubMed  Google Scholar 

  66. Gernand AD, Simhan HN, Klebanoff MA, Bodnar LM (2013) Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study. J Clin Endocrinol Metab 98(1):398–404. https://doi.org/10.1210/jc.2012-3275

    Article  CAS  PubMed  Google Scholar 

  67. Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM (2013) Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ 346:f1169. https://doi.org/10.1136/bmj.f1169

    Article  PubMed  Google Scholar 

  68. Morley R, Carlin JB, Pasco JA, Wark JD (2006) Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab 91(3):906–912. https://doi.org/10.1210/jc.2005-1479

    Article  CAS  PubMed  Google Scholar 

  69. Eggemoen ÅR, Jenum AK, Mdala I, Knutsen KV, Lagerløv P, Sletner L (2017) Vitamin D levels during pregnancy and associations with birth weight and body composition of the newborn: a longitudinal multiethnic population-based study. Br J Nutr 117(7):985–993. https://doi.org/10.1017/S000711451700068X

    Article  CAS  PubMed  Google Scholar 

  70. Wei SQ, Qi HP, Luo ZC, Fraser WD (2013) Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 26(9):889–899. https://doi.org/10.3109/14767058.2013.765849

    Article  CAS  PubMed  Google Scholar 

  71. Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K (2012) Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod 27(11):3321–3327. https://doi.org/10.1093/humrep/des280

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by a research grant from the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of Huazhong University of Science and Technology (no. 5001519002).

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Contributions

KM, SS, HZ, and AL conceived the study, collected the data, and wrote the manuscript. HL, DH, HZ and YC performed the literature search, collected and analyzed the data. AL administered the project, including designing, supervising, revising and final approval. All authors participated in the research significantly and critically appraised, revised and approved the manuscript.

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Correspondence to Ai-Hua Liao.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, "Low vitamin D levels in follicular fluid, but not in serum, are associated with adverse outcomes in assisted reproduction.

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The study protocol was approved by the Ethical Committee of Tongji Medical College of Huazhong University of Science and Technology. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Muyayalo, K.P., Song, S., Zhai, H. et al. Low vitamin D levels in follicular fluid, but not in serum, are associated with adverse outcomes in assisted reproduction. Arch Gynecol Obstet 305, 505–517 (2022). https://doi.org/10.1007/s00404-021-06174-9

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