ADA activity in the follicular fluid of infertile women with diminished ovarian reserve can act as a predictor of ovarian reserve

Gülşah İlhan, Besim H. Bacanakgil, Ayşe Köse, Ayben Atıcı, Şener Yalçınkaya, Mevlüde Ayyıldız


Background: Adenosine deaminase (ADA) catalyses the deamination of adenosine to inosine. In the human reproductive tract, the importance of enzymes that affect metabolism of adenosine, particularly ADA, has been emphasized. It is aimed to evaluate the plasma and follicular fluid (FF) activities of total ADA (ADAT) in infertile women and to determine its relation with ovarian reserve markers and in vitro fertilization (IVF) outcomes.

Methods: Plasma and FF activities of ADAT were measured in 106 infertile women. Its relation with ovarian reserve markers and IVF outcomes were determined.

Results: There was a significant difference in the ADAT activities between plasma and FF of infertile women (p<0.01). The activity of plasma ADAT was higher than FF ADAT in infertile women (p<0.01). The activity of FF ADAT in DOR group was higher than that of the others (p<0.01). In DOR group; the activity of FF ADAT activity had a negative correlation with BMI and a positive correlation with FSH and no relation with IVF outcomes.

Conclusions: Increased ADAT activity can lead to reduced adenosine levels, which might be resulted in disturbed fertility process. The activity of FF ADAT activity might be important for fertility work-up. Further studies are needed.


ADA, Diminished ovarian reserve, Follicular fluid, Infertility

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Muraoka T, Katsuramaki T, Shiraishi H, Yokoyama M. Automated enzymatic measurement of adenosine deaminase isoenzyme activities in serum. Anal Biochem. 1990;187:268-72.

Gakis C. Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: diagnostic and biological role. Eur Respir J. 1996;9:632-3.

Skarar DN, Hossain I, Shoab AKM, Amin R. Adenosine Deaminase (ADA) in Tuberculous Meningitis. Bangladesh J Med. 2014;25:61-71.

Mishra SK, Sah JP, Awasthi G, Sharma R. Adenosine deaminase activity in plasma of children with acute lymphoblastic leukemia. J Nepal Health Res Counc. 2009;7:93-7.

Adams A, Harkness RA. Adenosine deaminase activity in thymus and other human tissues. Clin Exp Immunol. 1976;26:647-9.

Kobayashi F, Ikeda T, Marumo F, Sato C. Adenosine deaminase isoenzymes in liver disease. Am J Gastroenterol. 1993;88:266-71.

Gakis C, Calia G, Naitana A, Pirino D, Serru G. Serum adenosine deaminase activity in HIV positive subjects: a hypothesis on the significance of ADA2. Panminerva Med. 1989;31:107-13.

Monks N, Fraser L. Inhibition of adenosine-metabolizing enzymes modulates mouse sperm fertilizing ability: a changing role for endogenously generated adenosine during capacitation. Gamete Res 1988;21:267-76.

Crabbe M. The development of a qualitative assay for male infertility from a study of enzymes in human semen. J Reprod Fertil. 1977;51:73-6.

Minelli A, Allegrucci C, Piomboni P, Mannucci R, Lluis C, Franco R. Immunolocalization of A1 adenosine receptors in mammalian spermatozoa. J Histochem Cytochem. 2000;48:1163-71.

Rostampour F, Biglari M, Vaisi-Raygani A, Salimi S, Tavilani H. Adenosine deaminase activity in fertile and infertile men. Andrologia. 2012;44(1):586-9.

Hitoglou S, Zournatzi V, Gougoustamou D, Hatzistilianou M, Tzafettas J. Adenosine deaminase activity and its isoenzyme pattern in women with recurrent spontaneous abortions. Gynecol Obstet Invest. 2004;58:126-9.

Nicotra M, Bottini N, La Torre M, Amante A, Bottini E, Gloria‐Bottini F. Repeated spontaneous abortion. Cooperative effects of ADA and ACP1 genetic polymorphisms. Am J Reprod Immunol. 2007;58(1):1-10.

Setarehbadi R, Hosseinipanah SM, Vatannejad A, Karimi M, Vaisi-Raygani A, Tavilani H. Adenosine deaminase activity during menses, follicular and luteal phases of the menstrual cycle. Eur J Obstet Gynecol Reprod Biol. 2011;155:233-4.

Yoneyama Y, Suzuki S, Sawa R, Otsubo Y, Miura A, Kuwabara Y, et al. Serum adenosine deaminase activity and its isoenzyme pattern in women with normal pregnancies. Arch Gynecol Obstet. 2003;267:205-7.

Mokhtari M, Hashemi M, Yaghmaei M, Molashahi F, Shikhzadeh A, Niazi A, et al. Serum adenosine deaminase activity in gestational diabetes mellitus and normal pregnancy. Arch Gynecol Obstet. 2010;281:623-6.

Lee S, Hwang H, Kim B, Kim M, Lee J, Park Y, et al. Changes in serum adenosine deaminase activity during normal pregnancy. J Korean Med Sci. 2007;22:718-21.

Tong J, Sheng S, Sun Y, Li H, Li WP, Zhang C, et al. Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve. Reproduction. 2017;153(4):443-51.

Rao M, Zhou F, Tang L, Zeng Z, Hu S, Wang Y, et al. Follicular fluid humanin concentration is related to ovarian reserve markers and clinical pregnancy after IVF-ICSI: a pilot study. Reprod Biomed Online. 2019;38(1):108-17.

de la Barca JMC, Boueilh T, Simard G, Boucret L, Ferré-L'Hotellier V, Tessier L, et al. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve. Hum Reprod. 2017;32(11):2269-78.

Cavallo IK, Dela Cruz C, Oliveira ML, Del Puerto HL, Dias JA, Lobach VN, et al. Angiotensin-(1-7) in human follicular fluid correlates with oocyte maturation. Hum Reprod. 2017;32:1318-24.

Buyuk E, Asemota OA, Merhi Z, Charron MJ, Berger DS, Zapantis A, et al. Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study. Fertil Steril. 2017;107:632-40.

Giusti G, Galanti B. Colorimetric method. In: Methods of Enzymatic Analysis, 3rd edn. Germany Verlag Chemie, Weinheim: Berlin; 1984:315-323.

Ferraretti A, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of ‘poor response'to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616-24.

Rad SS, Abbasalizadeh S, Haghjo AG, Sadagheyani M, Montaseri A, Rad JS. Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women. Int J Reprod Biol Med. 2015;13:439-44.

Aydın GA, Yavuz A, Terzi H, Kutlu T. Assessment of the relationship of basal serum anti-Mullerian hormone levels with oocyte quality and pregnancy outcomes in patients undergoing ICSI. Int J Reprod Biol Med. 2015;13:231-6.

Tal R, Seifer DB. Ovarian reserve testing: a user's guide. Am J Obstet Gynecol. 2017;217(2):129-40.

Loukides JA, Loy AR, Edwards R, Honig J, Visintin I, Polan ML. Human follicular fluids contain tissue macrophages. J Clin Endocrinol Metab. 1990;71(5):1363-7.

Celik E, Celik O, Kumbak B, Yilmaz E, Turkcuoglu I, Simsek Y, et al. Comparative study on oxidative and antioxidative markers of serum and follicular fluid in GnRH agonist and antagonist cycles. J Assist Reprod Genet. 2012;29(11):1175-83.

Hatzistilianou M, Antoniades D, Zournatzi V, Pappa S, Antoniades M, Koiou K, et al. Isoenzymes of adenosine deaminase and metalloproteinases as biomarkers in in vitro fertilization and embryo transfer. Int J Immunopathol Pharmacol. 2011;24(1):25-31.