Cover
Vol. 14 No. 1 (2024)

Published: June 30, 2024

Pages: 86-110

Research Article

Evaluation of SFRP5 Role in Relevance to BMI in Prediction of Pregnancy in a Sample of Iraqi Infertile Females Undergoing ICSI

Abstract

There is a relation between adipose tissue and macrophages. These macrophage cells influence adipose tissue by releasing many bioactive chemicals, including the wingless-type MMTV integration site family 5a (wnt5a) glycopeptides and the more traditional cytokines. Healthy adipocytes can release the wnt5a inhibitor Secreted frizzled-related protein 5(SFRP5). However, this protective effect was found to be reduced in obesity. This study aimed to assess the effect of follicular and serum levels of SFRP5 as well as serum and follicular levels of wnt5a on ICSI outcome and determine the potential roles of SFRP5 as a predictor of positive pregnancy in Iraqi infertile females undergoing ICSI with different body mass index .Ninety infertile females who received intracytoplasmic sperm injection and had various infertility factors between 18 and 45 years participated in this prospective clinical cross-sectional study. Follicular fluid, serum SFRP5, and serum and follicular fluid wnt5a levels were measured for all participants on the day of ovum pickup. In addition, ICSI outcomes were determined. There was a significant difference in the mean total gonadotrophin dose used among the three studied groups (p = 0.023), higher in overweight and obese females than normal-weight females. There was a positive significant correlation between serum plus follicular fluid wnt5a and total gonadotropin dose. Serum and follicular fluid SFRP5 levels were significantly higher in normal-weight females. There were higher serum (p-value=0.002) and follicular fluids (p-value=0.005) SFRP5 levels in pregnant females. Both SFRP5 and wnt5a glycoproteins were detected in infertile women's serum and follicular fluid. Serum and follicular fluid secreted frizzled-related protein 5 level positively associated with ICSI outcome. The cutoff values for serum and follicular fluid SFRP5 were ≥15.86 (ng/ml) and ≥ 11.3(ng/ml), respectively, as predictors of positive pregnancy in women undergoing IVF/ICSI cycles. Obesity, BMI, SFRP5, wnt5a, ICSI Outcome

References

  1. Wang H, Wang J, Liu T, Leng Y, Yang W. Stem cell-derived exosomal MicroRNAs: Potential therapies in diabetic kidney disease. Biomedicine & Pharmacotherapy. 2023 Aug 1;164:114961. https://doi.org/10.1016/j.biopha.2023.114961
  2. Al-yasiry RZ, Jwad MA, Hasan MF, Alsayigh HA. How obesity affects female fertility. Med j Babylon. 2022 Apr 1; 19:111. DOI: 10.4103/MJBL.MJBL_8_22
  3. García-Ferreyra J, Carpio J, Zambrano M, Valdivieso-Mejía P, Valdivieso-Rivera P. Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing in vitro fertilization procedures. JBRA Assisted Reproduction. 2021 Jul;25(3):394. DOI: 10.5935/1518- 0557.20200105
  4. Inal ZO, Inal HA, Erdem S. The effect of serum and follicular fluid secreted frizzle- related protein-5 on in vitro fertilization outcomes in patients with polycystic ovary syndrome. Molecular biology reports. 2018 Dec; 45:2037-2044. DOI: 10.1007/s11033- 018-4360-z
  5. Mohsin HAH, Mossa HAL, Jawad MA. The impact of serum and follicular fluid secreted frizzled-related protein-5 on ICSI outcome in Iraqi infertile women with different body mass index. Biomedicine. 2023;43(4):1239-1246. Doi: 10.51248/.v43i4.3109.
  6. Rydzewska M, Nikołajuk A, Matulewicz N, Stefanowicz M, Karczewska-Kupczewska M. Serum secreted frizzled-related protein 5 in relation to insulin sensitivity and its regulation by insulin and free fatty acids. Endocrine. 2021 Nov; 74:300-307. DOI:10.1007/s12020-021-02793-z
  7. Relling I, Akcay G, Fangmann D, Knappe C, Schulte DM, Hartmann K, Müller N, Türk K, Dempfle A, Franke A, Schreiber S. Role of wnt5a in metabolic inflammation in humans. The Journal of Clinical Endocrinology & Metabolism. 2018 Nov;103(11):4253-4264 . DOI: 10.1210/jc.2018-01007
  8. Al Hourani HM, Alkhatib B. Anthropometric indices of obesity as predictors of high blood pressure among school children. Clinical and Experimental Hypertension. 2022 Jan 2;44(1):11-19. https://doi.org/10.1080/10641963.2021.1969 662
  9. Magaton IM, Helmer A, Eisenhut M, Roumet M, Stute P, von Wolff M. Oocyte maturity, oocyte fertilization, and cleavage- stage embryo morphology are better in natural compared with high-dose gonadotrophin stimulated IVF cycles. Reproductive biomedicine online. 2023 Apr 1;46(4):705- 712 . DOI: 10.1016/j.rbmo.2022.11.008
  10. Zhang Y, Li Z, Ren B, Wu W, Liu Y, Wang X, Guan Y, Jia L. Diagnostic value of a single β-hCG test in predicting reproductive outcomes in women undergoing cleavage embryo transfer: a retrospective analysis from a single center. Reproductive Health. 2022 Dec;19(1):1-9 . DOI: 10.1186/s12978-022- 01455-1
  11. Pengpid S, Peltzer K. Overweight and obesity among adults in iraq: prevalence and correlates from a national survey in 2015. International journal of environmental research and public health. 2021 Apr 15;18(8):4198 . DOI:10.3390/ijerph18084198
  12. Shabu, S.A., 2019. Prevalence of overweight/obesity and associated factors in adults in Erbil, Iraq: A household survey. Zanco Journal of Medical Sciences (Zanco J Med Sci), 23(1), pp.128-134 . https://doi.org/10.15218/zjms.2019.017
  13. Jasim HM, Hussein HM, Al-Kaseer EA. Obesity among females in Al-Sader city Baghdad, Iraq, 2017. Journal of the Faculty of Medicine Baghdad. 2018 Sep 2;60(2):105- 107. DOI:https://doi.org/10.32007/jfacmedbagdad .60215
  14. Gautam, D., Purandare, N., Maxwell, C.V., Rosser, M.L., O'Brien, P., Mocanu, E., McKeown, C., Malhotra, J., McAuliffe, F.M. and FIGO Committee on Impact of Pregnancy on Long‐term Health and the FIGO Committee on Reproductive Medicine, Endocrinology and Infertility, 2023. The challenges of obesity for fertility: A FIGO literature review. International Journal of Gynecology & Obstetrics, 160, pp.50-55. DOI: 10.1002/ijgo.14538
  15. Marinelli S, Napoletano G, Straccamore M, Basile G. Female obesity and infertility: outcomes and regulatory guidance. Acta Bio Medica: Atenei Parmensis. 2022;93 ( 4 .) . doi: 10.23750/abm.v93i4.13466
  16. Dornelles VC, Hentschke MR, Badalotti M, Telöken IB, Trindade VD, Cunegatto B, de Vasconcelos NF, da Costa BE, Petracco A, Padoin AV. The impact of body mass index on laboratory, clinical outcomes and treatment costs in assisted reproduction: a retrospective cohort study. BMC Women's Health. 2022 Dec;22(1):1-8 . DOI: 10.1186/s12905-022-02036-x
  17. Christensen MW, Ingerslev HJ, Degn B, Kesmodel US. Effect of female body mass index on oocyte quantity in fertility treatments (IVF): Treatment cycle number is a possible effect modifier. A register-based cohort study. PLoS One. 2016 Sep 21;11(9):e0163393. 10.1371/journal.pone.0163393
  18. Li Y, Jiang Y, Zhang S, Liu H, Zhang C. Association of HOMA-IR with ovarian sensitivity index in women undergoing IVF/ICSI: a retrospective cohort study. Diabetes, Metabolic Syndrome and Obesity. 2023 Dec 31:309-20. doi: 10.3389/fendo.2023.1117996
  19. Dawood SA, Jwad MA, Mossa HAL. The impact of serum and follicular fluid irisin on oocyte and embryonic characteristics in infertile women undergoing ICSI according to BMI. Al-Rafidain J Med Sci. 2023;5:211- 217. doi: https://doi.org/10.54133/ajms.v5i.224.
  20. Abedini A, Zamberlam G, Boerboom D, Price CA. Non-canonical WNT5A is a potential regulator of granulosa cell function in cattle. Molecular and Cellular Endocrinology. 2015 Mar 5; 403:39-45 . https://doi.org/10.1016/j.mce.2015.01.017
  21. Hu KL, Wang S, Ye X, Zhang D, Hunt S. GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials. Reproductive Biology and Endocrinology. 2021 Dec;19(1):1-0. DOI: 10.1186/s12958-021-00766-5
  22. He X, Ma H. Correlation between circulating levels of secreted frizzled-related protein 5 and type 2 diabetic patients and subjects with impaired-glucose regulation. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020; 13:1243. doi: 10.2147/DMSO.S242657
  23. Akoumianakis I, Sanna F, Margaritis M, Badi I, Akawi N, Herdman L, Coutinho P, Fagan H, Antonopoulos AS, Oikonomou EK, Thomas S. Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases. Science translational medicine. 2019 Sep 18;11(510): eaav5055. DOI: 10.1126/scitranslmed.aav5055
  24. Carstensen-Kirberg M, Kannenberg JM, Huth C, Meisinger C, Koenig W, Heier M, Peters A, Rathmann W, Roden M, Herder C, Thorand B. Inverse associations between serum levels of secreted frizzled-related protein-5 (SFRP5) and multiple cardiometabolic risk factors: KORA F4 study. Cardiovascular Diabetology. 2017 Dec;16(1):1-0. DOI https://doi.org/10.1186/s12933-017-0591-x
  25. Black MH, Shu YH, Wu J, Koebnick C, MacKay A, Watanabe RM, Buchanan TA, Xiang AH. Longitudinal increases in adiposity contribute to worsening adipokine profile over time in Mexican Americans. Obesity. 2018 Apr;26(4):703-12 . DOI: 10.1002/oby.22128
  26. Koutaki D, Michos A, Bacopoulou F, Charmandari E. The emerging role of Sfrp5 and Wnt5a in the pathogenesis of obesity: implications for a healthy diet and lifestyle. Nutrients. 2021 Jul 19;13(7):2459. doi: 10.3390/nu13072459
  27. Motawi TK, Shaker OG, Ismail MF, Sayed NH. Peroxisome proliferator-activated receptor gamma in obesity and colorectal cancer: the role of epigenetics. Scientific reports. 2017 Sep 6;7(1):1-8. DOI https://doi.org/10.1038/s41598-017-11180-6
  28. Liu X, Shi S, Sun J, He Y, Zhang Z, Xing J, Chong T. The influence of male and female overweight/obesity on IVF outcomes: a cohort study based on registration in Western China. Reproductive Health. 2023 Jan 2;20(1):3 . DOI: 10.1186/s12978-022-01558-9
  29. Amiri M, Tehrani FR. Potential adverse effects of female and male obesity on fertility: a narrative review. International journal of endocrinology and metabolism. 2020 Jul;18 ( 3 .) . https://doi.org/10.5812/ijem.101776
  30. Ruebel ML, Piccolo BD, Mercer KE, Pack L, Moutos D, Shankar K, Andres A. Obesity leads to distinct metabolomic signatures in follicular fluid of women undergoing in vitro fertilization. American Journal of Physiology-Endocrinology and Metabolism. 2019 Mar 1;316(3): E383-96.
  31. Song J, Xiang S, Pang C, Guo J, Sun Z. Metabolomic alternations of follicular fluid of obese women undergoing in-vitro fertilization treatment. Scientific Reports. 2020 Apr 6;10(1):5968
  32. Akoumianakis I, Polkinghorne M, Antoniades C. Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications. Nature Reviews Cardiology. 2022 Jun 13:1- 5 .
  33. Huang X, Yan Y, Zheng W, Ma Y, Wang X, Gong W, Nie S. Secreted frizzled-related protein 5 protects against cardiac rupture and improves cardiac function through inhibiting mitochondrial dysfunction. Frontiers in Cardiovascular Medicine. 2021 Sep 9; 8:682409.
  34. Chen F, Chen Y, Mai Q. Multi-Omics Analysis and Machine Learning Prediction Model for Pregnancy Outcomes After Intracytoplasmic Sperm Injection–in vitro Fertilization. Front. Public Health. 2022 Jun 30; 10:924539
  35. Akino R, Matsui D, Kawahara-Miki R, Amita M, Tatsumi K, Ishida E, Kang W, Takada S, Miyado K, Sekizawa A, Saito T. Next-generation sequencing reveals downregulation of the Wnt signaling pathway in human dysmature cumulus cells as a hallmark for evaluating oocyte quality. Reproductive Medicine. 2020 Dec 1;1(3):205-215.
  36. Habara O, Logan CY, Kanai-Azuma M, Nusse R, Takase HM. WNT signaling in pre- granulosa cells is required for ovarian folliculogenesis and female fertility. Development. 2021 May 1;148(9): dev198846..