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Insertion / deletion polymorphism of angiotensin-converting enzyme gene in ovarian hyperstimulation syndrome patients

Year 2019, , 13 - 22, 18.01.2019
https://doi.org/10.31362/patd.415288

Abstract

Purpose: Previous
studies have shown that ovary contains all the components
of renin-angiotensin system. Renin-angiotensin system may play a primary role
in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). In this study
our purpose was to investigate the relationship between the
angiotensin-converting enzyme (ACE) gene polymorphism and OHSS in high risk patients for the syndrome.

Materials and methods:  47 patients who have undergone controlled
ovarian hyperstimulation cycle (control n: 25; OHSS n: 22) were recruited in
the study. Estradiol levels of all patients in both group were higher than 3000
pg/ml . Age, duration of infertility, total gonadotropin dose, induction time,
total follicular number, endometrial thickness and cause of infertility were recorded.
DNA was extracted, and the insertion/deletion polymorphism of ACE gene was
detected by polymerase chain reaction (PCR).

Results: There were no
statistically difference in age, duration of infertility, total gonadotropin
dose, induction time and endometrial thickness between control and OHSS group.
Follicle number was higher in OHSS group (p<0,001).
There
were no difference in the ACE  II – ID – DD  genotypes
between OHHS and control group patients (p>0,05). Homozygotes for the
deletion polymorphism (DD genotype) were found 1,47 times higher in OHSS group (OR: 1,47 %95 confidence interval, 0,44 - 4,86) but this was statistically
insignificant.







Conclusion: These data
indicate that ACE gene I/D polymorphism is not associated with OHSS. ACE gene
polymorphism doesn’t play a major role in the pathogenesis of OHSS.

References

  • 1. Delvigne A, Rozenberg S. Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS). Human Reproduction Update 2003;9.1:77-96.
  • 2. Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome. Journal of human reproductive sciences 2011;4.2: 70-5.
  • 3. Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 1978;30(3):255-68
  • 4. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44(6):430-40.
  • 5. Golan A, Weissman A. Symposium: Update on prediction and management of OHSS. a modern classification of OHSS. Reprod Biomed Online 2009;19(1):28-32.
  • 6. Jenkins, JM, Drakeley AJ, Mathur RS. The management of ovarian hyperstimulation syndrome. RCOG Green Top Guideline no. 5, 2006. Reconfirmed 2016.
  • 7. Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril 1992;58(2):249-61.
  • 8. McElhinney B, McClure N. Ovarian hyperstimulation syndrome. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14(1):103-22.
  • 9. Humaidan P, Nelson SM, Devroey P, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod 2016;31(9):1997-2004.
  • 10. Yarali H, Fleige-Zahradka BG, Yuen BH, McComb PF. The ascites in the ovarian hyperstimulation syndrome does not originate from the ovary. Fertil Steril 1993;59(3):657-61.
  • 11. Soares SR, Gómez R, Simón C, García-Velasco JA, Pellicer A. Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome. Hum Reprod Update 2008;14(4):321-33.
  • 12. Navot D, Margalioth EJ, Laufer N, et al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril 1987;48(1):57-61.
  • 13. Frederick JL, Shimanuki T, diZerega GS. Initiation of angiogenesis by human follicular fluid. Science 1984;224(4647):389-90.
  • 14. Fernandez LA, Tarlatzis BC, Rzasa PJ, et al. Renin-like activity in ovarian follicular fluid. Fertil Steril 1985;44(2):219-23.
  • 15. Ong AC, Eisen V, Rennie DP, et al. The pathogenesis of the ovarian hyperstimulation syndrome (OHS: a possible role for ovarian renin. Clin Endocrinol (Oxf)1991;34(1):43-9.
  • 16. Delbaere A, Bergmann PJ, Gervy-Decoster C, Staroukine M, Englert Y. Angiotensin II immunoreactivity is elevated in ascites during severe ovarian hyperstimulation syndrome: implications for pathophysiology and clinical management. Fertil Steril 1994;62(4):731-7.
  • 17. Mamiatis T, Fritsch EF, Sambrook J, Engel J. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1982
  • 18. Shanmugam V, Sell KW, Saha BK. Mistyping ACE heterozygotes. PCR Methods Appl 1993;3(2):120-1.
  • 19. Erdös EG, Skidgel RA. The angiotensin I-converting enzyme. Lab Invest 1987;56(4):345-8.
  • 20. Jaffe SB, Jaffe LH, Jewelewicz R. Incidence of severe ovarian hyperstimulation syndrome with extremely elevated serum estrogen levels. Gynecol Obstet Invest 1993;35(4):222-7.
  • 21. Gonçalves PB, Ferreira R, Gasperin B, Oliveira JF. Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances. Reproduction 2012;143(1):11-20.
  • 22. Ezra Y, Simon A, Yaron A, Laufer N, Navot D. Angiotensin-I-converting enzyme and its correlation with human follicular fluid steroids. Eur J Obstet Gynecol Reprod Biol 1992;44(1):71-5.
  • 23. Itskovitz-Eldor J, Kol S, Lewit N, Sealey JE. Ovarian origin of plasma and peritoneal fluid prorenin in early pregnancy and in patients with ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 1997;82(2):461-4.
  • 24. Vinson GP, Saridogan E, Puddefoot JR, Djahanbakhch O. Tissue renin-angiotensin systems and reproduction. Hum Reprod 1997;12(4):651-62.
  • 25. Palumbo A, Ávila J, Naftolin F. The ovarian renin-angiotensin system (OVRAS): a major factor in ovarian function and disease. Reprod Sci 2016;23(12):1644-1655.
  • 26. Delbaere A, Bergmann PJ, Gervy-Decoster C, Deschodt-Lanckman M, de Maertelaer V, Englert Y. Periovulatory elevation of angiotensin II in the peritoneal fluid during the human menstrual cycle. J Clin Endocrinol Metab 1996;81(8):2810-5.
  • 27. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86(4):1343-6.
  • 28. Heiskanen JT, Pirskanen MM, Hiltunen MJ, Mannermaa AJ, Punnonen KR, Heinonen ST. Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia. Am J Obstet Gynecol 2001;185(3):600-3.
  • 29. Balasch J, Arroyo V, Fábregues F,et al. Neurohormonal and hemodynamic changes in severe cases of the ovarian hyperstimulation syndrome. Ann Intern Med 1994;121(1):27-33.
  • 30. Balasch J, Fábregues F, Arroyo V. Peripheral arterial vasodilation hypothesis: a new insight into the pathogenesis of ovarian hyperstimulation syndrome. Hum Reprod 1998;13(10):2718-30.

Ovaryan hipersimulasyon sendromlu hastalarda anjiotensin dönüştürücü enzim geni insersiyon / delesyon polimorfizmi

Year 2019, , 13 - 22, 18.01.2019
https://doi.org/10.31362/patd.415288

Abstract

Amaç: Ovaryan hiperstimulasyon
sendromu (OHSS) riski altındaki hastalarda, anjiotensin dönüştürücü enzim (ACE)
gen insersiyon / delesyon (I/D) polimorfiziminin ovaryan hiperstimulasyon
sendromu gelişiminde etkisinin olup olmadığının belirlenmesidir.

Gereç ve
yöntem:
Yardımcı üreme teknikleri tedavisi için ovulasyon indüksiyon programına
alınan, ve human koryonik gonadotropin yapıldığı gün estradiol seviyesi 3000
pg/ml’den fazla olan, OHSS gelişimi için yüksek risk altında bulunan 47
infertil hasta dahil edildi. Hastaların yaşı, infertilite süresi, kullanılan
total gonadotropin dozu, indüksiyon süresi, elde edilen folikül sayısı,
endometriyum kalınlığı ve infertilite nedeni kaydedildi. Kontrol (n:25) ve OHSS
(n:22) grubu hastalarının ACE genine ait insersiyon/delesyon polimorfizmi, PCR
yöntemiyle çalışılarak tesbit edildi.

Bulgular: Yaş,
infertilite süresi, gonadotropin dozu, indüksiyon süresi, endometriyum kalınlık
ölçümleri iki grup arasında anlamlı farklılık göstermedi. Folikül sayısı
kontrol grubunda 17,1 ± 4,2 OHSS
grubunda 25,4 ± 6,8 olarak bulundu. Her iki grup arasında bulunan fark
anlamlıdır (p<0,001). OHSS
grubunda ACE geni D allel frekansı %56,8 kontrol grubunda %54,0 ve toplam 47
hastadaki D allel frekansı %55,3 olarak bulundu. OHSS ve kontrol grubu ACE
genotipi için karşılaştırıldığında iki grup arasında II – ID – DD genotipleri
bakımından anlamlı fark bulunmamıştır(p>0,05).
OHSS grubunda genotipin DD olma olasılığı, kontrol grubuna gore 1,47 kat daha
yüksektir (OR: 1,47 %95 Güven Sınırı, 0,44-4,86) fakat istatistiksel olarak
anlamlı değildir.







Sonuç: Çalışmada OHSS için
yüksek riskli hastalarda ACE gen insersiyon/delesyon polimorfizmi
çalışılmıştır. DD genotipinin oranı OHSS ve kontrol grubunda farklı değildir.
ACE gen insersiyon/delesyon polimorfizminin, OHSS gelişiminde etken faktör
olarak değerlendirilmemiştir.

References

  • 1. Delvigne A, Rozenberg S. Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS). Human Reproduction Update 2003;9.1:77-96.
  • 2. Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome. Journal of human reproductive sciences 2011;4.2: 70-5.
  • 3. Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 1978;30(3):255-68
  • 4. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44(6):430-40.
  • 5. Golan A, Weissman A. Symposium: Update on prediction and management of OHSS. a modern classification of OHSS. Reprod Biomed Online 2009;19(1):28-32.
  • 6. Jenkins, JM, Drakeley AJ, Mathur RS. The management of ovarian hyperstimulation syndrome. RCOG Green Top Guideline no. 5, 2006. Reconfirmed 2016.
  • 7. Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril 1992;58(2):249-61.
  • 8. McElhinney B, McClure N. Ovarian hyperstimulation syndrome. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14(1):103-22.
  • 9. Humaidan P, Nelson SM, Devroey P, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod 2016;31(9):1997-2004.
  • 10. Yarali H, Fleige-Zahradka BG, Yuen BH, McComb PF. The ascites in the ovarian hyperstimulation syndrome does not originate from the ovary. Fertil Steril 1993;59(3):657-61.
  • 11. Soares SR, Gómez R, Simón C, García-Velasco JA, Pellicer A. Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome. Hum Reprod Update 2008;14(4):321-33.
  • 12. Navot D, Margalioth EJ, Laufer N, et al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril 1987;48(1):57-61.
  • 13. Frederick JL, Shimanuki T, diZerega GS. Initiation of angiogenesis by human follicular fluid. Science 1984;224(4647):389-90.
  • 14. Fernandez LA, Tarlatzis BC, Rzasa PJ, et al. Renin-like activity in ovarian follicular fluid. Fertil Steril 1985;44(2):219-23.
  • 15. Ong AC, Eisen V, Rennie DP, et al. The pathogenesis of the ovarian hyperstimulation syndrome (OHS: a possible role for ovarian renin. Clin Endocrinol (Oxf)1991;34(1):43-9.
  • 16. Delbaere A, Bergmann PJ, Gervy-Decoster C, Staroukine M, Englert Y. Angiotensin II immunoreactivity is elevated in ascites during severe ovarian hyperstimulation syndrome: implications for pathophysiology and clinical management. Fertil Steril 1994;62(4):731-7.
  • 17. Mamiatis T, Fritsch EF, Sambrook J, Engel J. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1982
  • 18. Shanmugam V, Sell KW, Saha BK. Mistyping ACE heterozygotes. PCR Methods Appl 1993;3(2):120-1.
  • 19. Erdös EG, Skidgel RA. The angiotensin I-converting enzyme. Lab Invest 1987;56(4):345-8.
  • 20. Jaffe SB, Jaffe LH, Jewelewicz R. Incidence of severe ovarian hyperstimulation syndrome with extremely elevated serum estrogen levels. Gynecol Obstet Invest 1993;35(4):222-7.
  • 21. Gonçalves PB, Ferreira R, Gasperin B, Oliveira JF. Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances. Reproduction 2012;143(1):11-20.
  • 22. Ezra Y, Simon A, Yaron A, Laufer N, Navot D. Angiotensin-I-converting enzyme and its correlation with human follicular fluid steroids. Eur J Obstet Gynecol Reprod Biol 1992;44(1):71-5.
  • 23. Itskovitz-Eldor J, Kol S, Lewit N, Sealey JE. Ovarian origin of plasma and peritoneal fluid prorenin in early pregnancy and in patients with ovarian hyperstimulation syndrome. J Clin Endocrinol Metab 1997;82(2):461-4.
  • 24. Vinson GP, Saridogan E, Puddefoot JR, Djahanbakhch O. Tissue renin-angiotensin systems and reproduction. Hum Reprod 1997;12(4):651-62.
  • 25. Palumbo A, Ávila J, Naftolin F. The ovarian renin-angiotensin system (OVRAS): a major factor in ovarian function and disease. Reprod Sci 2016;23(12):1644-1655.
  • 26. Delbaere A, Bergmann PJ, Gervy-Decoster C, Deschodt-Lanckman M, de Maertelaer V, Englert Y. Periovulatory elevation of angiotensin II in the peritoneal fluid during the human menstrual cycle. J Clin Endocrinol Metab 1996;81(8):2810-5.
  • 27. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86(4):1343-6.
  • 28. Heiskanen JT, Pirskanen MM, Hiltunen MJ, Mannermaa AJ, Punnonen KR, Heinonen ST. Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia. Am J Obstet Gynecol 2001;185(3):600-3.
  • 29. Balasch J, Arroyo V, Fábregues F,et al. Neurohormonal and hemodynamic changes in severe cases of the ovarian hyperstimulation syndrome. Ann Intern Med 1994;121(1):27-33.
  • 30. Balasch J, Fábregues F, Arroyo V. Peripheral arterial vasodilation hypothesis: a new insight into the pathogenesis of ovarian hyperstimulation syndrome. Hum Reprod 1998;13(10):2718-30.
There are 30 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Cihan Kabukçu 0000-0003-3331-5714

Gülşen Vardar This is me

Publication Date January 18, 2019
Submission Date April 14, 2018
Acceptance Date October 2, 2018
Published in Issue Year 2019

Cite

AMA Kabukçu C, Vardar G. Ovaryan hipersimulasyon sendromlu hastalarda anjiotensin dönüştürücü enzim geni insersiyon / delesyon polimorfizmi. Pam Tıp Derg. January 2019;12(1):13-22. doi:10.31362/patd.415288
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