Effectiveness of folic acid in unexplained infertility


  • Sujata Narendra Jadhav Department of Family Medicine, 171 MH Samba, Jammu and Kashmir, India
  • Devdatt Laxman Pitale Department of Obstetrics and Gynecology, INHS ASVINI, Mumbai, Maharashtra, India




Conception, Folic acid, Infertility


Background: Folic acid is commonly used by infertile women worldwide. However, studies on the effect of folic acid in women with unexplained infertility are lacking. This aim of this study was to evaluate the effectiveness of folic acid in women with unexplained infertility.

Methods: This prospective multicentric study was performed from June 2019 to July 2020 in women with unexplained infertility attending the fertility clinic. In this study, 50 women with unexplained infertility who satisfied the inclusion and exclusion criteria were started on folic acid therapy. The effectiveness of therapy was evaluated on the basis of successful conception and adverse effects if any.

Results: Folic acid therapy showed a marked improvement in infertility status measured in terms of successful conception. After initial 12 weeks therapy successful conception was achieved in 40 (80%) women without any adverse effects.

Conclusions: Folic acid supplementation has a positive effect on pregnancy outcome in women with unexplained infertility without any adverse effects. Folic acid is thus a safe and cost-effective option in women with unexplained infertility.

Author Biographies

Sujata Narendra Jadhav, Department of Family Medicine, 171 MH Samba, Jammu and Kashmir, India


Maternal Care wing and Family OPD

171 Military Hospital

Devdatt Laxman Pitale, Department of Obstetrics and Gynecology, INHS ASVINI, Mumbai, Maharashtra, India

Surgeon Lieutenant Commander

Assistant Professor in Obstetrics and Gynaecology





Vayena E, Rowe PJ, Griffin PD. (Eds.), current practices and controversies in assisted reproduction. WHO, Geneva; 2002.

Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000;71:1295S-303S.

Hassan MA, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertil Steril. 2004;81:384-92.

Raine-Fenning NJ, Campbell BK, Kendall NR, Clewes JS, Johnson IR. Endometrial and subendometrial perfusion are impaired in women with unexplained subfertility. Hum Reprod. 2004;19:2605-14.

Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr. 2006;83:993-1016.

Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13:163-74.

Antony AC. In utero physiology: role of folic acid in nutrient delivery and fetal development. Am J Clin Nutr. 2007;85:598S-603S.

Molloy AM, Scott JM. Folates and prevention of disease. Public Health Nutr. 20001;4:601-9.

Nilsen RM, Vollset SE, Rasmussen SA, Ueland, PM, Daltveit AK. Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study. Am J Epidemiol. 2008;167:867-74.

Safi J, Joyeux L, Chalouhi GE. Periconceptional folate deficiency and implications in neural tube defects. J Pregnancy. 2012:295083.

Wilcox AJ, Lie RT, Solvoll K, Taylor J, Mcconnaughey DR, Abyholm F, et al. Folic acid supplements and risk of facial clefts: national population-based case-control study. BMJ. 2007;334:464.

Boxmeer JC, Brouns RM, Lindemans J, Steegers EA, Martini E, Macklon NS, et al. Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans. Fertil Steril. 2008;89:1766-70.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett, WC. Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility. Fertil Steril. 2008;89:668-76.

Brouwer IA, Van Dusseldorp M, Thomas CM, Duran M, Hautvast JG, Eskes TK. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr. 1999;69:99-104.

Boxmeer JC, Macklon NS, Lindemans J, Beckers NG, Eijkemans MJ, Laven JS, et al. IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid. Hum Reprod. 2009;24:1059-66.

Haggarty P, McCallum H, McBain H, Andrews K, Duthie S, McNeill G, et al. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet. 2006;367:1513-9.

Mcguire M, Cleary B, Sahm L, Murphy DJ. Prevalence and predictors of periconceptional folic acid uptake - prospective cohort study in an Irish urban obstetric population. Hum Reprod. 2010;25:535-43.

De Walle HE, De Jong-Van Den Berg LT. Ten years after the Dutch public health campaign on folic acid: the continuing challenge. Eur J Clin Pharmacol. 2008;64:539-43.

Zestra-Van Der Woude PA, De Walle HE, De Jong-Van Den Berg LT. Periconceptional folic acid use: still room to improve. birth defects research (part A): clinical and molecular. Birth Defects Res A Clin Mol Teratol. 2012;94:96-101.

Lane IR. Preventing neural tube defects with folic acid: nearly 20 years on, the majority of women remain unprotected. J Obstet Gynaecol. 2011;31:581-5.

Elkin AC, Higham J. Folic acid supplements are more effective than increased dietary folate intake in elevating serum folate levels. BJOG. 2000;107:285-9.

Mcnulty H, Pentieva K. Folate bioavailability. Proc Nutr Soc. 2004:63:529-36.

is common and increases disease risk. It can be corrected by daily ingestion of supplements or fortification. Novartis Found. Symp. 2007;282:105-17.






Original Research Articles