Subsidiary programs reproductive technologies: clinical outcomes and impact vitamin D
AbstractAim - to assess the correlation of vitamin D Levels in various biological fluids of infertile women with reproductive technologies (ART) outcomes, age and ovarian reserve (OR) condition.
Material and methods. 147 patients of senior reproductive age with tubal-peritoneal infertility were analysed. Patients being 36-44 years old were included in the study, own oocytes in "fresh" cycles and cryoprotocol and normozoospermia were used. Patients were stratified into groups: 1st - with pregnancy (n=37), 2nd - with negative outcomes in assisted ART programs (n=110). In 2nd group, oocytes and/or embryos were not obtained in 32 women. Level 25(OH)D in serum and follicular fluid (FF) in groups with obtained embryos (n=115) and unreceived oocytes and/or embryos (n=32) was assessed. 53 in vitro fertilization (IVF) and 94 IVF/IntraCytoplasmic Sperm Injection (ICSI) programs were carried out.
Results. Women with a favorable outcome in the IVF and IVF-ICSI programs were distinguished by optimal vitamin D indicators - 89.2% in the blood and all - in FF. Negative IVF and IVF-ICSI outcomes revealed in the group with of women with different vitamin D content in the blood serum: within the range of 20-30 ng/ml - 42.3%, optimal value ≥30 ng/ml - 37.3%, <20 ng/ml - 4.5%, excessive one (>150 ng/ml) - in FF in both groups. In a group with the clinical pregnancy amount of women with vitamin D content in the blood serum ≥30 ng/ml appeared practically twice as much, what with the uneffective IVF and IVF-ICSI attempts (89.2 and 37.3% accordingly, p=0.009). Amount of infertile women with vitamin D in FF in the range of ≥30 ng/ml appeared more than in the serum of blood (100.0 and 61.8% accordingly). In groups with ineffective outcomes of ART programs the comparable amount of women had a level 25(0H)D in a range 20-30 ng/ml both in the blood serum and FF (42.3 and 36.4% accordingly). Pregnancy at insufficiency of vitamin of D in the blood serum took place for 10.8% women (p=0.008).
The mean value of vitamin of D in FF exceeded indexes in the blood serum, in a greater degree - at the favourable outcomes of ART programs (p=0.003). An analogical tendency was traced in regard to groups with the got embryos is a level 25(OH)D in FF appeared higher, than in the serum of blood in default of similar differences for women with the adverse outcomes of protocols IVF and IVF-ICSI (p=0.2).
Conclusions. The content of 25(OH)D in FF generally reflects that in the body. The concentration of 25(OH)D in blood serum and FF is correlative, with a higher FF vitamin content in the group with clinical pregnancy compared to unsuccessful IVF outcomes. No relationship was found between the level of 25(OH)D and the level of Anti-Muller hormone, the number of follicles, the quality and number of oocytes and embryos. The absence of pregnancy in the group with an optimal 25(OH)D level indicates the need for an expanded search for the causes of negative outcomes.
Keywords:infertile women, vitamin D (25(OH)D), IVF, IVF-ICSI, follicular fluid, Anti-Muller hormone
Funding. The study had no sponsor support.
Conflict of interests. The authors declare no conflict of interests.
For citation: Voropaeva E.E., Chukhnina E.G., Kazachkova E.A., Kazachkov E.L., Polina M.L. Subsidiary programs reproductive technologies: clinical outcomes and impact vitamin D. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2020; 8 (3): 29-38. DOI: 10.24411/2303-9698-2020-13004 (in Russian)
References
1. Palacios C., Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014; 144 (pt A): 138-45. DOI: https://doi.org/10.1016/j.jsbmb.2013.11.003
2. Holick M.F., Binkley N.C., Bischoff-Ferrari H.A., et al. Evaluation, treatment, and prevention of vitamin D deficiency: Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96 (7): 1911-30. DOI: https://doi.org/10.1210/jc.2011-0385
3. Castro L.C. The vitamin D endocrine system. Arq Bras Endocrinol Metabol. 2011; 55 (8): 566-75. DOI: https://doi.org/10.1590/S000427302011000800010
4. Parikh G., Varadinova M., Suwandhi P., Araki T., et al. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res. 2010; 42 (10): 754-7. DOI: https://doi.org/10.1055/s-0030-1262837
5. Wehr E., Trummer O., Giuliani A., Gruber H.J., et al. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011; 164: 741-9. DOI: https://doi.org/10.1530/EJE-11-0134
6. Blomberg Jensen M., Dissing S. Non-genomic effects of vitamin D in human spermatozoa. Steroids. 2012; 77 (10): 903-9. DOI: https://doi.org/10.1016/j.ste-roids.2012.02.020
7. Clinic recommendations for vitamin D deficiency in adults. Russian Association of Endocrinologists. Moscow: FGBU «Endokrinniy nauchniy tsentr» Ministerstva zdravookhraneniya Rossii, 2015. (in Russian)
8. Kalychenko S.J., Gilenko M.I., Gusakov D.A., Tyzikov R., et al. Vitamin D and reproductive health of women. Problemy reproduktsii [Problems of Reproduction]. 2016; 22 (4): 28-36. DOI: https://doi.org/10.17116/repro201622428-36 (in Russian)
9. Lerchbaum E., Obermayer-Pietsch B. Mechanisms in endocrinology: vitamin D and fertility: a systematic review. Eur J Endocrinol. 2012; 166 (5): 765-78. DOI: https://doi.org/10.1530/eje-11-0984
10. Anagnostis P., Karras S., Goulis D.G. Vitamin D in human reproduction: a narrative review. Int J Clin Pract. 2013; 67 (3): 225-35. DOI: https://doi.org/10.1111/ijcp.12031
11. Wagner C.L., Taylor S.N., Dawodu A., Johnson D.D., et al. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients. 2012; 4 (3): 208-30. DOI: https://doi.org/10.3390/nu4030208
12. Merhi Z., Doswell A., Krebs K., Cipolla M. Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells. J Clin Endocrinol Metab. 2014; 99 (6): е1137-45. DOI: https://doi.org/10.1210/jc.2013-4161
13. Dennis N.A., Houghton L.A., Jones G.T., van Rij A.M., et al. The level of serum anti-Mullerian hormone correlates with vitamin D status in men and women but not in boys. J Clin Endocrinol Metab. 2012; 97: 2450-5. DOI: https://doi.org/10.1210/jc.2012-1213
14. Cappy H., Giacobini P., Pigny P., Bruyneel A., et al. Low vitamin D3 and high anti-MCllerian hormone serum levels in the polycystic ovary syndrome (PCOS): Is there a link? Ann Endocrinol (Paris). 2016; 77 (5): 593-9. DOI: https://doi.org/10.1016/j.ando.2016.02.001
15. Drakopoulos P., van de Vijver A., Schutyser V., Milatovic S., et al. The effect of serum vitamin D levels on ovarian reserve markers: a prospective cross-sectional study. Hum Reprod. 2017; 32 (1): 208-14. DOI: https://doi.org/10.1093/humrep/dew304
16. Aleyasin A., Hosseini M.A., Mahdavi A., Safdarian L., et al. Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol. 2011; 159 (1): 132-7. DOI: https://doi.org/10.1016/j.ejogrb.2011.07.006
17. Wojtusik J., Johnson P.A. Vitamin D regulates anti-Mullerian hormone expression in granulose cells of the hen. Biol Reprod. 2012; 86: 91. DOI: https://doi.org/10.1095/biolreprod.111.094110
18. Rajaei S., Mirahmadian M., Jeddi-Tehrani M., Tavakoli M., et al. Effect of 1, 25 (OH) 2 vitamin D3 on cytokine production by endometrial cells of women with repeated implantation failure. Gynecol Endocrinol. 2012; 28 (11): 906-11. DOI: https://doi.org/10.3109/09513590.2012.683062
19. Polyzos N.P., Anckaert E., Guzman L., Schiettecatte J., et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Hum Reprod. 2014; 29 (9): 2032-40. DOI: https://doi.org/10.1093/humrep/deu156
20. Naimi Z.M.S., Kalinina E.A., Donnikov A.E., Dudarova A.Kh. Association of vitamin D receptor (VDR) gene polymorphism with embryological characteristics and effectiveness of in vitro fertilization programs. Akusherstvo i ginekologiya [Obstetrics and Gynecology]. 2017; (2): 51-7. DOI: https://doi.org/10.18565/aig.2017.2.51-7 (in Russian)
21. Rudick B., Ingles S., Stanczyk F., Chung K., et al. Characterizing the role of vitamin D levels on IVF outcomes: stimulation, embryo, or endometrium? Fertil Steril. 2010; 94 (4): 72. DOI: https://doi.org/10.1016/j.fertnstert.2010.07.280
22. Rudick B., Ingles S., Chung K., Stanczyk F., et al. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod. 2012; 27: 3321-7. DOI: https://doi.org/10.1093/humrep/des280
23. Lv S.S., Ji Y.W., Wang X.Q., Wang Y., et al. Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016; 293: 1339-45. DOI:https://doi.org/10.1007/s00404-016-4058-1
24. Neville G., Martyn F., Kilbane M., O’Riordan M., et al. Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intra-cytoplasmic sperm injection. Int J Gynecol Obstet. 2016; 135 (2): 172-6. DOI: https://doi.org/10.1016/j.ijgo.2016.04.018
25. Anifandis G.M., Dafopoulos K., Messini C.I., Chalvatzas N., et al. Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol. 2010; 8: 91. DOI: https://doi.org/10.1186/1477-7827-8-91
26. Pacis M.M., Fortin C.N., Zarek S.M., Mumford S.L., et al. Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review. J Assist Reprod Genet. 2015; 32 (3): 323-35. DOI: https://doi.org/10.1007/s10815-014-0407-9
27. Firouzabadi R.D., Rahmani E., Rahsepar M., Firouzabadi M.M. Value of follicular fluid vitamin D in predicting the pregnancy rate in an IVF program. Arch Gynecol Obstet. 2014; 289 (1): 201-6. DOI: https://doi.org/10.1007/s00404-013-2959-9
28. Zhao J., Huang X., Xu B., et al. Whether vitamin D was associated with clinical outcome after IVF/ICSI: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2018; 16 (1): 13. DOI: https://doi.org/10.1186/s12958-018-0324-3
29. Franasiak J.M., Molinaro T.A., Dubell E.K., Scott K.L., et al. Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts. Am J Obstet Gynecol. 2015; 212 (3): 315.e1-6. DOI: https://doi.org/10.1016/j.ajog.2014.09.029
30. van de Vijver A., Drakopoulos P., Van Landuyt L., Vaiarelli A., et al. Vitamin D deficiency and pregnancy rates following frozen-thawed embryo transfer: a prospective cohort study. Hum Reprod. 2016; 31 (8): 1749-54. DOI: https://doi.org/10.1093/humrep/dew107
31. Vanni V.S., Vigano P., Somigliana E., Papaleo E., et al. Vitamin D and assisted reproduction technologies: current concepts. Reprod Biol Endocrinol. 2014; 12: 47. DOI: https://doi.org/10.1186/1477-7827-12-47
32. Lv S.S., Ji Y.W., Wang X.Q., Wang Y., et al. Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016; 293: 1339-45. DOI: https://doi.org/10.1007/s00404-016-4058-1
33. Ozkan S., Jindal S., Greenseid K., Shu J., et al. Replete vitamin D stores predict reproductive success followingin vitro fertilization. Fertil Steril. 2010; 94: 1314-9. DOI: https://doi.org/10.1016/j.fertnstert.2009.05.019
34. Farzadi L., Bidgoli H.K., Ghojazadeh M., Bahrami Z., et al. Correlation between follicular fluid 25-OH vitamin D and assisted reproductive outcomes. Iran J Reprod Med. 2015; 13 (6): 361-6.
35. Abadia L., Gaskins A.J., Chiu Y.H., Williams P.L., et al. Serum 25-hydro-xyvitamin D concentrations and treatment outcomes of women undergoing assisted reproduction. Am J Clin Nutr. 2016; 104 (3): 729-35. DOI: https://doi.org/10.3945/ajcn.115.126359
36. Du H., Daftary G.S., Lalwani S.I., Taylor H.S. Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol. 2005; 19: 2222-33.