Serum vitamin D and anti- mullerian hormone levels in Iraqi infertile women at Baghdad city
Keywords:Vitamin D, Female Infertility, Anti- Mullerian Hormone, Mullerian Inhibiting Substance, Ovarian Reserve.
Background: Reproductive failure is a significant public health concern. Although relatively little is known about factors affecting fertility, a growing body of literature suggests that environmental & lifestyle factors play an important role. Recent studies suggest that vitamin D may play a role in human reproduction. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remains far from clear.
Objective: To validate the potential of vitamin D as a biomarker for prediction of female infertility and to study the correlation between vitamin D and Anti- Mullerian hormone.
Methods: A case- control study was conducted at Department of Chemistry and Biochemistry, College of Medicine, Al- Nahrain University, Al- Kadhmiya, Baghdad, Iraq from June 2013 till July 2014. Seventy three subjects were enrolled in this study. Thirty five primary infertile women with mean age (25.4± 4.91 years), and thirty eight age- matched apparently healthy women as controls with mean age (27.3±3.72 years). Fasting blood samples were collected in the morning at 8:00 am from all participants. Vitamin D was measured by high-performance liquid chromatography technique and Anti- Mullerian hormone was measured by enzyme- linked immunosorbent assay.
Results: Vitamin D levels was significantly decreased in the infertile women group compared with fertile control group (35.38±5.83 ng/ mL) versus (49.99±12.90 ng/ mL) respectively. Vitamin D correlated significantly (r = +0.86; p â‰¤ 0.05) with anti-mullerian hormone and anti- mullerian hormone shows a significant negative correlation with body mass index (r = -0.78; p â‰¤ 0.05).
Conclusion: A novel relationship was found between circulating Anti- Mullerian hormone and vitamin D in plasma samples of infertile women.
 Luk J, Torrealday S, Neal Perry G, Pal L. Relevance of vitamin D in reproduction. Hum Reprod. 2012; 27:3015â€“3027. http://dx.doi.org/10.1093/humrep/des248.
 Anagnostis P, Karras S, Goulis DG. Vitamin D in human reproduction: a narrative review. Int J Clin Pract 2013; 67(3): 225- 235. http://dx.doi.org/10.1111/ijcp.12031.
 Lieben L, Carmeliet G, Masuyama R. Calcemic actions of vitamin D: effect on the intestine, kidney and bone. Best Pract Res Clin Endocrinol Metab 2011; 25: 561- 72. http://dx.doi.org/10.1016/j.beem.2011.05.008.
 Grundmann M, von Versen- HÓ§ynck F. Vitamin D- roles in women's reproductive health? Reproductive biology and endocrinology. 2011, 9: 146. http://dx.doi.org/10.1186/1477-7827-9-146.
 Alpert PT, Shaikh U. The effects of vitamin D deficiency on the endocrine and paracrine systems. Biol Res Nurs. 2007; 9(2): 117-129. http://dx.doi.org/10.1177/1099800407308057.
 Dokoh S, Donaldson CA, Marion SL, Pike JW, Haussler MR. The ovary a target for 1, 25-dihydroxyvitamin D3. Endocrinology 1983; 112(1): 200-206. http://dx.doi.org/10.1210/endo-112-1-200.
 Halloran BP, Deluca HF.Effect of vitamin D deficiency on fertility and reproduction capacity in the female rat. J. Nut 1980; 110(8): 1573-1580.
 Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidant exposure and impact on female fertility. Human reproduction update 2008; 14(2): 345-357. http://dx.doi.org/10.1093/humupd/dmn011.
 Hamade A, Bhanini S, Saade T, Fakih Y, Fakih C, Azzi R, Hazouri M, Rizk F. Vitamin D levels in serum, vitamin D receptor polymorphisms and semen quality correlations in Lebanon: A pilot cross- sectional study. Universal journal of public health 2014; 2(4): 118- 124.
 Poornima BN, Govindraju NL, Bhat SK. Vitamin D acts as bio- marker for predicting IVF success: A case study. International research journal of biological sciences 2014; 3(9): 97- 99.
 Patel M, Jain S, Jain D, Patel B, Phanse N, Vyas P, Rathore P. Prevalence of different factors responsible for infertility. Res J Recent Sci 2012; 1: 207- 211.
 Lerchbaum E, Obermayer- Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol 2012; 166: 765- 778. http://dx.doi.org/10.1530/EJE-11-0984.
 Merhi OZ, Seifer BD, Weedon J, Adeyemi OHRN, Anastos KGTE, Young MKR, et al. Circulating vitamin D correlates with serum anti- mullerian hormone levels in late reproductive aged women. Women's Interagency HIV study. Fertil Steril 2012; 98: 228- 234. http://dx.doi.org/10.1016/j.fertnstert.2012.03.029.
 Vigier B, Tran D, Legeai L, Bezard J, Josso N. Origin of anti- mullerian hormone in bovine freemartin fetuses. J Reprod Fertil 1984; 70: 473-479. http://dx.doi.org/10.1530/jrf.0.0700473.
 Saglam F, Onal ED, Erosy R, Koca C, Ergin M, Erel O, Cakir B. Anti- mullerian hormone as a marker of premature ovarian aging in autoimmune thyroid disease. Gynecol Endocrinol 2014, Early online: 1- 4.
 Van Rooij IA, Tonkelaar I, Broekmans FJ, Looman CW, Scheffer GJ, de Jong FH, Themmen AP, te Velde ER. Anti- mullerian hormone is a promising predictor for the occurrence of the menopausal transition. Menopause 2004; 11: 601-606. http://dx.doi.org/10.1097/01.GME.0000123642.76105.6E.
 Van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH, Themmen AP. Serum anti- mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod 2002; 17: 3065- 3071. http://dx.doi.org/10.1093/humrep/17.12.3065.
 Van Disseldorp J, Broekmans FJ, Peeters PH, Fauser BC, van der Schouw YT. The association between vascular function related genes and age at natural menopause. Menopause 2008; 15: 511-516. http://dx.doi.org/10.1097/gme.0b013e31814cec52.
 Szafarowska M, Molinska- Glura M, Jerzak MM. Anti- mullerian hormone concentration as a biomarker of pregnancy success or failure. Neuroendocrinology letters 2014; 35(4): 322- 326.
 Pilz S, Dobnig H, Winklhofer- Roob B, Riedmuller G, Fischer JE, Seelhorst U, et al. Low serum levels of 25- hydroxyvitamin D predict fatal cancer in patients referred to coronary angiography. Cancer Epidemiology, Biomarkers and Prevention 2008; 17: 1228- 1233. http://dx.doi.org/10.1158/1055-9965.EPI-08-0002.
 Holick MF. Vitamin D deficiency. New England Journal of Medicine 2007; 357: 266- 281. http://dx.doi.org/10.1056/NEJMra070553.
 Pilz S, MÃ¤rz W, Wellnitz B, Seelhorst U, Fahrleitner- Pammer A, Dimai HP, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross- sectional study of patients referred for coronary angiography. J Clin Endo Metabol 2008; 93: 3927- 3935. http://dx.doi.org/10.1210/jc.2008-0784.
 Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer- Pietsch B. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 2009; 161: 575- 582. http://dx.doi.org/10.1530/EJE-09-0432.
 Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S, Messinis IE. Prognostic value of follicular fluid 25- OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endo 2010; 8: 91. http://dx.doi.org/10.1186/1477-7827-8-91.
 Garbedian K, Boggild M, Moody J, Liu KE. Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. Canadian Medical Association Journal 2013; 1(2): E77- E82. http://dx.doi.org/10.9778/cmajo.20120032.
 Ozkan S, Jindal S, Greenseid K, Shu J, Zeittian G, Hickmon C, Pal L. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 2010; 94(4): 1314- 1319. http://dx.doi.org/10.1016/j.fertnstert.2009.05.019.
 Zhang C, Qiu C, Hu FB, David RM,van Dam RM, Bralley A, Williams MA. Maternal plasma 25- hydroxyvitamin D concentrations and the risk for gestational diabetes mellitus. PLoS one 2008; 3(11): e3753. http://dx.doi.org/10.1371/journal.pone.0003753.
 Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab 2009; 94(3): 940- 945. http://dx.doi.org/10.1210/jc.2008-1217.
 Li L, Schriock E, Dougall K, Givens C. Prevalence and risk factors of vitamin D deficiency in women with infertility. Pacific Fertility Center, San Francisco, CA.
 Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25- hydroxyl vitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metabol 2006; 91(3): 906- 912. http://dx.doi.org/10.1210/jc.2005-1479.
 Vigano P, Lattuada D, Mangioni S, Ermellino L, Vignali M, Caporizzo E, et al. Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. Journal of Molecular Endocrinology 2006; 36: 415- 424. http://dx.doi.org/10.1677/jme.1.01946.
 Malloy PJ, Peng L, Wang J, Feldman D. Interaction of the vitamin D receptor with a vitamin D response element in the mullerian- inhibiting substance (MIS) promoter: Regulation of MIS expression by calcitriol in prostate cancer cells. Endocrinology 2009; 150: 1580- 1587. http://dx.doi.org/10.1210/en.2008-1555.
 Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L, et al. Vitamin D regulates steroidogenesis and insulin- like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Hormone and Metabolic Research 2010; 42: 754- 757. http://dx.doi.org/10.1055/s-0030-1262837.
 Barrera D, Avila E, Henandez G, Mendez I, Gonzalez I, Halhali A, et al. Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts. Reproductive Biology and Endocrinology 2008; 6:3. (doi: 10.1186/1477-7827-6-3) http://dx.doi.org/10.1186/1477-7827-6-3.
 Barrera D, Avila E, Henandez G, Halhali A, Biruete B, Larrea F, et al. Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. Journal of Steroid Biochemistry and Molecular Biology 2007; 103: 529- 532. http://dx.doi.org/10.1016/j.jsbmb.2006.12.097.
 Du H, Daftary GS, Lalwani SI, Taylor HS. Direct regulation of HOXA10 by 1, 25-(OH) 2D3 in human myelomonocytic cells and human endometrial stromal cells. Molecular Endocrinology 2005; 19: 2222- 2233. http://dx.doi.org/10.1210/me.2004-0336.
 Bagot CN, Troy PI, Taylor HS. Alteration of maternal HOXA10 expression by in vivo gene transfection affects implantation. Gene Therapy 2000; 7: 1378- 1384. http://dx.doi.org/10.1038/sj.gt.3301245.
 Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, et al. Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clinical Chemistry 2005; 51: 1691- 1697. http://dx.doi.org/10.1373/clinchem.2005.052761.
 Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, et al. Low serum 25- hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Experimental and Clinical Endocrinology and Diabetes 2006; 114: 577- 583. http://dx.doi.org/10.1055/s-2006-948308.
 Kamycheva E, Joakimsen RM, Jorde R. Intakes of calcium and vitamin D predict body mass index in the population of Northern Norway. Journal of Nutrition 2003; 133: 102- 106.
 Pittas AG, Lau J, Hu FB, Dawson- Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 2007; 92: 2017- 2029. http://dx.doi.org/10.1210/jc.2007-0298.
 Maestro B, Davila N, Carranza MC, Calle C. Identification of a vitamin D response element in the human insulin receptor gene promoter. Journal of Steroid Biochemistry and Molecular Biology 2003; 84: 223- 230. http://dx.doi.org/10.1016/S0960-0760(03)00032-3.
 Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25- dihydroxyvitamin D3. Cell Biochemistry and function 2002; 20: 227- 232. http://dx.doi.org/10.1002/cbf.951.