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Serumda ve Foliküler Sıvıdaki Gebelikle İlişkili Plazma Protein-A (PAPP-A) Değerlerinin Embriyo Gelişimi ve Erken Gebelik Sonuçları ile İlişkisi

Year 2019, Volume: 6 Issue: 2, 75 - 80, 29.08.2019

Abstract

Bu çalışmada, oosit toplanması sırasında elde edilen folikül sıvısında ve serumda Gebelikle İlişkili Plazma Protein-A (PAPP-A) bakılması, bunun oosit maturasyonu, embriyo gelişimi ve erken gebelik sonuçları ile ilişkisinin değerlendirilmesi amaçlanmıştır. Tek merkezde yürütülmüş olan bu prospektif kohort çalışmasına, intrasitoplazmik sperm enjeksiyonu (ICSI) ve embriyo transferi (ET) uygulanan 55 hasta dâhil edilmiştir. Tüm hastalara uzun agonist protokol kullanılarak ovulasyon indüksiyonu yapılmıştır. Her hastanın iki ayrı folikülünden elde edilen folikül sıvılarından ve oosit toplanması sırasında alınan kanlarından Floresan immunoassay (FIA) yöntemi ile PAPP-A seviyeleri ölçülmüştür. Bu foliküllerden elde edilen işaretli oositlerin matürasyon ve fertilizasyonları değerlendirilmiş ve bunlardan oluşan embriyoların gelişimi takip edilmiştir. PAPP-A düzeylerinin embriyo kaliteleri ve gebelik oranları ile ilişkisi değerlendirilmiştir. Folikül sıvılarında bakılan PAPP-A değerleri ile aynı foliküllerden elde edilen embriyo kaliteleri arasında anlamlı bir ilişki saptanmamıştır. Embriyolar kalitelerine göre ayrıldığında, elde edildikleri foliküllerin PAPP-A değerleri arasındaki fark da anlamlı bulunmamıştır. Ancak, gebelik oluşan hastalarda oosit toplanması sırasında serumda bakılan PAPP-A değerleri gebelik oluşmayan hastalardakine göre anlamlı olarak düşük saptanmıştır (p<0.05). Folikül sıvısındaki PAPP-A seviyeleri embriyo kalitesi ve gebelik oranları ile anlamlı olarak ilişkili bulunmadı. Serum PAPP-A değerleri ise gebelik oluşan ve oluşmayan hastalar arasında anlamlı olarak farklı bulundu. Ancak, daha geniş hasta popülasyonu ile çalışmalar yapılmalıdır.

References

  • 1. Wang TH, Chang CL, Wu HM, Chiu YM, Chen CK, Wang HS. Insulin-like growth factor-II (IGF-II), IGF-binding protein-3 (IGFBP-3), and IGFBP-4 in follicular fluid are associated with oocyte maturation and embryo development. Fertil Steril. 2006;86:1392-401.
  • 2. Oosterhuis GJE, Vermes I, Lambalk CB, Michgelsen HWB, Schoemaker J. Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles. Hum Reprod. 1998;13:285-9.
  • 3. Nicholas B, Alberio R, Fouladi-Nashta AA, Webb R. Relationship Between Low-Molecular-Weight Insulin-Like Growth Factor-Binding Proteins, Caspase-3 Activity, and Oocyte Quality. Biol Reprod. 2005;72:796-804.
  • 4. Fried G, Wramsby H, Tally M. Transforming growth factor-β1, insulin-like growth factors, and insulin-like growth factor binding proteins in ovarian follicular fluid are differentially regulated by the type of ovarian hyperstimulation used for in vitro fertilization. Fertil Steril. 1998;70:129-34.
  • 5. Fortune JE, Rivera GM, Yang MY. Follicular development: the role of the follicular microenvironment in selection of the dominant follicle. Anim Reprod Sci. 2004;82-83:109-26.
  • 6. Monget P, Mazerbourg S, Delpuech T, et al. Pregnancy-Associated Plasma Protein-A Is Involved in Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) Proteolytic Degradation in Bovine and Porcine Preovulatory Follicles: Identification of Cleavage Site and Characterization of IGFBP-2 Degradation. Biol Reprod. 2003;68:77-86.
  • 7. Rivera GM, Fortune JE. Selection of the Dominant Follicle and Insulin-Like Growth Factor (IGF)-Binding Proteins: Evidence that Pregnancy-Associated Plasma Protein A Contributes to Proteolysis of IGF-Binding Protein 5 in Bovine Follicular Fluid. Endocrinology. 2003;144(2):437-46.
  • 8. Besnard N, Pisselet C, Zapf J, Hornebeck W, Monniaux D, Monget P. Proteolytic activity is involved in changes in intrafollicular insulinlike growth factor-binding protein levels during growth and atresia of ovine ovarian follicles. Endocrinology. 1996; 137:1599-607.
  • 9. Chandrasekher YA, Van Dessel HJHM, Fauser BCJM, Giudice LC. Estrogen- but not androgen-dominant human ovarian follicular fluid contains an insulin-like growth factor binding protein-4 protease. J Clin Endocrinol Metab. 1995;80:2734–9.
  • 10. Conover CA, Oxvig C, Overgaard MT, Christiansen M, Giudice LC. Evidence that the insulin-like growth factor binding protein-4 protease in human ovarian follicular fluid is pregnancy associated plasma protein-A. J Clin Endocrinol Metab. 1999;84:4742–5.
  • 11. Choi YS, Ku SY, Jee BC, et al. Comparison of follicular fluid IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A concentrations and their ratios between GnRH agonist and GnRH antagonist protocols for controlled ovarian stimulation in IVF-embryo transfer patients. Hum Reprod. 2006;21:2015-21.
  • 12. Conover CA, Faessen GF, Ilg KE, et al. Pregnancy-Associated Plasma Protein-A is the Insulin-Like Growth Factor Binding Protein-4 Protease Secreted by Human Ovarian Granulosa Cells and Is a Marker of Dominant Follicle Selection and the Corpus Luteum. Endocrinology. 2001;142: 2155-8.
  • 13. Zhong G, Chen B. Serum and follicular fluid levels of IGF-II, IGF-binding protein-4 and pregnancy-associated plasma protein-A in controlled ovarian hyperstimulation cycle between polycystic ovarian syndrome (PCOS) and non-PCOS women. Gynecol Endocrinol. 2011;27(2):86-90.
  • 14. Kristensen SG, Mamsen LS, Jeppesen JV, et al. Hallmarks of Human Small Antral Follicle Development: Implications for Regulation of Ovarian Steroidogenesis and Selection of the Dominant Follicle. Front Endocrinol. 2018;8:376.
  • 15. Bøtkjær JA, Jeppesen JV, Wissing ML, et al. Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels. Fertil Steril. 2015;104(5):1294-301.
  • 16. Mazerbourg S, Monget P. Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System Regulating the Ovarian Folliculogenesis. Front Endocrinol. 2018;9:134.
  • 17. Zhou J, Wang J, Penny D, Monget P, Arraztoa JA, Fogelson LJ. Insulin-Like Growth Factor Binding Protein 4 Expression Parallels Luteinizing Hormone Receptor Expression and Follicular Luteinization in the Primate Ovary. Biol Reprod. 2003;69:22-9.
  • 18. Lighten AD, Hardy K, Winston RM, Moore GE. Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Mol Reprod Dev. 1997;47:134-9.
  • 19. Firouzabadi RD, Mohammadian F, Mashayekhy M, Davar R, Eftekhar M. The correlation between follicular fluid pregnancy-associated plasma protein A levels, fertilization, and embryo quality in GnRH agonist and GnRH antagonist protocols in ART cycles. Iran J Reprod Med. 2012;10(6):477-82.
  • 20. Stanger JD, Yovich JL, Grudzinskas JG, Bolton AE. Relation between pregnancy-associated plasma protein A (PAPP-A) in human peri-ovulatory follicle fluid and the collection and fertilization of human ova in vitro. Br J Obstet Gynaecol. 1985;92:786-92.
  • 21. Moos J, Filova V, Pavelkova J, Moosova M, Peknicova J, Rezabek K. Follicular fluid and serum levels of inhibin A and pregnancy-associated plasma protein A in patients undergoing IVF. Fertil Steril. 2009;91(5):1739-44.

Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results

Year 2019, Volume: 6 Issue: 2, 75 - 80, 29.08.2019

Abstract

The objective of this study is to measure Pregnancy Associated Plasma Protein-A (PAPP-A) in serum and follicular fluid during oocyte retrieval, and to investigate the association of PAPP-A with oocyte maturation, embryo development and early pregnancy results. This prospective cohort study was conducted in single center including fifty-five patients to whom intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) were applied. Long agonist protocol was applied for ovarian stimulation. Follicular fluid was aspirated from two separate follicules of each patient for oocyte retrieval and PAPP-A levels of follicular fluids and serum were measured via Fluorescence immunoassay (FIA). Marked oocytes from these follicles were evaluated for their maturation and fertilization and embryo development were followed. Association of PAPP-A levels with embryo quality and pregnancy rates were assessed. There was not statistically significant association between the follicular fluid PAPP-A levels and the embryo qualities obtained from the oocyte of the same follicle. Also, PAPP-A levels from follicles were not significantly different when compared between high and low quality embryos. In contrast, serum PAPP-A levels at the time of oocyte retrieval were significantly lower in patients who achieved pregnancy when compared to the patients at whom pregnancy was not achieved (p<0.05). PAPP-A level in follicular fluid was not significantly related to embryo quality and pregnancy rates while serum PAPP-A values were significantly different between patients who achieved pregnancy and the patients who could not achieve pregnancy. However, further studies with large number of patients are needed.

References

  • 1. Wang TH, Chang CL, Wu HM, Chiu YM, Chen CK, Wang HS. Insulin-like growth factor-II (IGF-II), IGF-binding protein-3 (IGFBP-3), and IGFBP-4 in follicular fluid are associated with oocyte maturation and embryo development. Fertil Steril. 2006;86:1392-401.
  • 2. Oosterhuis GJE, Vermes I, Lambalk CB, Michgelsen HWB, Schoemaker J. Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles. Hum Reprod. 1998;13:285-9.
  • 3. Nicholas B, Alberio R, Fouladi-Nashta AA, Webb R. Relationship Between Low-Molecular-Weight Insulin-Like Growth Factor-Binding Proteins, Caspase-3 Activity, and Oocyte Quality. Biol Reprod. 2005;72:796-804.
  • 4. Fried G, Wramsby H, Tally M. Transforming growth factor-β1, insulin-like growth factors, and insulin-like growth factor binding proteins in ovarian follicular fluid are differentially regulated by the type of ovarian hyperstimulation used for in vitro fertilization. Fertil Steril. 1998;70:129-34.
  • 5. Fortune JE, Rivera GM, Yang MY. Follicular development: the role of the follicular microenvironment in selection of the dominant follicle. Anim Reprod Sci. 2004;82-83:109-26.
  • 6. Monget P, Mazerbourg S, Delpuech T, et al. Pregnancy-Associated Plasma Protein-A Is Involved in Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) Proteolytic Degradation in Bovine and Porcine Preovulatory Follicles: Identification of Cleavage Site and Characterization of IGFBP-2 Degradation. Biol Reprod. 2003;68:77-86.
  • 7. Rivera GM, Fortune JE. Selection of the Dominant Follicle and Insulin-Like Growth Factor (IGF)-Binding Proteins: Evidence that Pregnancy-Associated Plasma Protein A Contributes to Proteolysis of IGF-Binding Protein 5 in Bovine Follicular Fluid. Endocrinology. 2003;144(2):437-46.
  • 8. Besnard N, Pisselet C, Zapf J, Hornebeck W, Monniaux D, Monget P. Proteolytic activity is involved in changes in intrafollicular insulinlike growth factor-binding protein levels during growth and atresia of ovine ovarian follicles. Endocrinology. 1996; 137:1599-607.
  • 9. Chandrasekher YA, Van Dessel HJHM, Fauser BCJM, Giudice LC. Estrogen- but not androgen-dominant human ovarian follicular fluid contains an insulin-like growth factor binding protein-4 protease. J Clin Endocrinol Metab. 1995;80:2734–9.
  • 10. Conover CA, Oxvig C, Overgaard MT, Christiansen M, Giudice LC. Evidence that the insulin-like growth factor binding protein-4 protease in human ovarian follicular fluid is pregnancy associated plasma protein-A. J Clin Endocrinol Metab. 1999;84:4742–5.
  • 11. Choi YS, Ku SY, Jee BC, et al. Comparison of follicular fluid IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A concentrations and their ratios between GnRH agonist and GnRH antagonist protocols for controlled ovarian stimulation in IVF-embryo transfer patients. Hum Reprod. 2006;21:2015-21.
  • 12. Conover CA, Faessen GF, Ilg KE, et al. Pregnancy-Associated Plasma Protein-A is the Insulin-Like Growth Factor Binding Protein-4 Protease Secreted by Human Ovarian Granulosa Cells and Is a Marker of Dominant Follicle Selection and the Corpus Luteum. Endocrinology. 2001;142: 2155-8.
  • 13. Zhong G, Chen B. Serum and follicular fluid levels of IGF-II, IGF-binding protein-4 and pregnancy-associated plasma protein-A in controlled ovarian hyperstimulation cycle between polycystic ovarian syndrome (PCOS) and non-PCOS women. Gynecol Endocrinol. 2011;27(2):86-90.
  • 14. Kristensen SG, Mamsen LS, Jeppesen JV, et al. Hallmarks of Human Small Antral Follicle Development: Implications for Regulation of Ovarian Steroidogenesis and Selection of the Dominant Follicle. Front Endocrinol. 2018;8:376.
  • 15. Bøtkjær JA, Jeppesen JV, Wissing ML, et al. Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels. Fertil Steril. 2015;104(5):1294-301.
  • 16. Mazerbourg S, Monget P. Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System Regulating the Ovarian Folliculogenesis. Front Endocrinol. 2018;9:134.
  • 17. Zhou J, Wang J, Penny D, Monget P, Arraztoa JA, Fogelson LJ. Insulin-Like Growth Factor Binding Protein 4 Expression Parallels Luteinizing Hormone Receptor Expression and Follicular Luteinization in the Primate Ovary. Biol Reprod. 2003;69:22-9.
  • 18. Lighten AD, Hardy K, Winston RM, Moore GE. Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Mol Reprod Dev. 1997;47:134-9.
  • 19. Firouzabadi RD, Mohammadian F, Mashayekhy M, Davar R, Eftekhar M. The correlation between follicular fluid pregnancy-associated plasma protein A levels, fertilization, and embryo quality in GnRH agonist and GnRH antagonist protocols in ART cycles. Iran J Reprod Med. 2012;10(6):477-82.
  • 20. Stanger JD, Yovich JL, Grudzinskas JG, Bolton AE. Relation between pregnancy-associated plasma protein A (PAPP-A) in human peri-ovulatory follicle fluid and the collection and fertilization of human ova in vitro. Br J Obstet Gynaecol. 1985;92:786-92.
  • 21. Moos J, Filova V, Pavelkova J, Moosova M, Peknicova J, Rezabek K. Follicular fluid and serum levels of inhibin A and pregnancy-associated plasma protein A in patients undergoing IVF. Fertil Steril. 2009;91(5):1739-44.
There are 21 citations in total.

Details

Primary Language English
Subjects Surgery
Journal Section Original Article
Authors

Gülşen Doğan Durdağ 0000-0002-5064-5267

Hakan Şatıroğlu This is me

Batuhan Özmen This is me 0000-0002-4504-669X

Ruşen Aytaç This is me 0000-0002-2644-545X

Cem Atabekoğlu This is me 0000-0003-0264-0709

Bülent Berker This is me 0000-0001-7346-7128

Murat Sönmezer 0000-0001-6101-1414

Publication Date August 29, 2019
Submission Date March 18, 2019
Published in Issue Year 2019 Volume: 6 Issue: 2

Cite

APA Doğan Durdağ, G., Şatıroğlu, H., Özmen, B., Aytaç, R., et al. (2019). Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 6(2), 75-80.
AMA Doğan Durdağ G, Şatıroğlu H, Özmen B, Aytaç R, Atabekoğlu C, Berker B, Sönmezer M. Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results. MMJ. August 2019;6(2):75-80.
Chicago Doğan Durdağ, Gülşen, Hakan Şatıroğlu, Batuhan Özmen, Ruşen Aytaç, Cem Atabekoğlu, Bülent Berker, and Murat Sönmezer. “Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid With Embryo Development and Early Pregnancy Results”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6, no. 2 (August 2019): 75-80.
EndNote Doğan Durdağ G, Şatıroğlu H, Özmen B, Aytaç R, Atabekoğlu C, Berker B, Sönmezer M (August 1, 2019) Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6 2 75–80.
IEEE G. Doğan Durdağ, “Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results”, MMJ, vol. 6, no. 2, pp. 75–80, 2019.
ISNAD Doğan Durdağ, Gülşen et al. “Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid With Embryo Development and Early Pregnancy Results”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 6/2 (August 2019), 75-80.
JAMA Doğan Durdağ G, Şatıroğlu H, Özmen B, Aytaç R, Atabekoğlu C, Berker B, Sönmezer M. Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results. MMJ. 2019;6:75–80.
MLA Doğan Durdağ, Gülşen et al. “Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid With Embryo Development and Early Pregnancy Results”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, vol. 6, no. 2, 2019, pp. 75-80.
Vancouver Doğan Durdağ G, Şatıroğlu H, Özmen B, Aytaç R, Atabekoğlu C, Berker B, Sönmezer M. Relation of Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Serum and Follicular Fluid with Embryo Development and Early Pregnancy Results. MMJ. 2019;6(2):75-80.