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POLİKİSTİK OVER SENDROMU OLAN VE OLMAYAN İNFERTİL OLGULARDA ENDOMETRİAL Bcl-2 EKSPRESYONU VE Ki-67 PROLİFERATİF İNDEKSİNİN DEĞERLENDİRİLMESİ

Year 2023, , 87 - 95, 31.03.2023

Dilay Karademir , Akın Usta , Eren Altun

https://doi.org/10.7197/cmj.1250217
An Erratum to this article was published on May 8, 2023. http://cmj.cumhuriyet.edu.tr/en/pub/cmj/issue/77213/1294036

Abstract

Amaç: Polikistik over sendromu (PKOS) üreme çağındaki kadınlarda görülen en sık infertilite nedenidir. Bu çalışmanın amacı; PKOS olan ve olmayan infertil hastalarda endometrial Bcl-2ve Ki-67 değerlerini biyokimyasal parametreler eşliğinde karşılaştırmaktır.
Yöntem: Çalışmaya PKOS teşhisi konulan 27 infertil hasta ve PKOS kriterlerine uymayan 28 infertil hasta dahil edildi. Çalışmadan dışlanma kriterleri; kişinin sigara kullanması, pelvik enfeksiyon bulgusu, transvajinal ultrasonografide endometrial polip, submüköz myom vb. saptanması, hipofizer yetmezlik, hiperprolaktinemi, konjenital adrenal hiperplazisi olmak, adneksiyal cerrahi geçirmiş olmak ve infertiliteye sebep olacak erkek faktörü bulunmaktır. Tüm bireylerin yaş, infertilite süresi, vücut- kitle indeksi (VKİ), bel-kalça oranı (BKO), hirsutizm skoru, kan basınçları, total testesteron, trigliserit, total kolesterol, LDL, HDL değerleri, HOMA-IR ve hs-CRP değerleri not edildi. Patoloji uzmanı tarafından Bcl-2ve Ki-67 düzeyleri değerlendirildi.
Bulgular: PKOS’lu infertil olgularda VKİ, BKO, total testosteron seviyesini, kan basıncını, total kolesterol değerini, HOMA-IR ve hs-CRP değerlerini belirgin yüksek bulduk. Ayrıca Ki-67 ve Bcl-2 değerinin PKOS’lu infertil olgularda endometriyal hücrelerde kontrol grubuna oranla daha yüksek olduğunu bulduk.
Sonuç: Ki-67 ve Bcl-2 değerleri, PKOS’lu olgularda artarak, apopitozisin gerçekleşmesini engeller ve uygun endometriyal ortam oluşmasını engellerek de embriyonun implantasyon sürecini kısıtlar. Bu durum PKOS’lu olgularda infertilite ve tekrarlayan gebelik kayıplarına neden olabilmektedir. Bu soruna artmış östrojen aktivitesi sebep olabilir. PKOS’un tedavisinde, östrojen salınımını düzenleyen, özellikle GnRH salınımını düzenleyici ajanlar üzerine çalışmalar yapılmasına ihtiyaç duyulduğu ve tedavinin bu hedef üzerine şekillenmesi gerektiği kanaatindeyiz.

Keywords

Bcl-2 Infertility Ki-67 Polycystic Ovary Syndrome

References

  • 1.Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106(1):6–15.
  • 2.Costello MF, Misso ML, Balen A, Boyle J, Devoto L,Garad RM, et al. A brief update on the evidence supporting infertility treatment in polycystic ovary syndrome. Aust New Zeal J Obstet Gynaecol. 2019;59(6):867–73.
  • 3.Al-Obaidi MT, Ali ZH, AL-Saadi WI, AL-Wasiti EAR, Al-Aubaidy H. Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with the polycystic ovarian syndrome. J Clin Pharm Ther. 2019;44(4):618–22.
  • 4.Maliqueo M, Clementi M, Gabler F, Johnson MC,Palomino A, Sir-Petermann T, et al. Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome. Fertil Steril. 2003;80(SUPPL. 2):812–9.
  • 5.Dabadghao P. Polycystic ovary syndrome inadolescents. Best Pract Res Clin Endocrinol Metab. 2019;33(3):101272.
  • 6.Dewailly D, Robin G, Peigne M, Decanter C, Pigny P,Catteau-Jonard S. Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update. 2016;22(6):709–24.
  • 7.Fauser BCJM, Tarlatzis BC, Rebar RW, Legro RS, BalenAH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38.e25.
  • 8.Yazıcı P, ALİZADEHSHARGH S, AKDOĞAN GG.Apopitoz: Düzenleyici Moleküller, Hastalıklarla İlişkisi ve Apopitozu Saptama Yöntemleri. Türkiye Klin Tıp Bilim Derg. 2009;29(6):1677–86.
  • 9.Paulson M, Norstedt G, Sahlin L, Hirschberg AL.Association between prolactin receptor expression and proliferation in the endometrium of obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2020;36(3):226–32.
  • 10.Piltonen TT. Polycystic ovary syndrome:Endometrial markers. Best Pract Res Clin ObstetGynecol. 2016;37(April):66–79.
  • 11.Sunkara SK, La Marca A, Seed PT, Khalaf Y.Increased risk of preterm birth and low birthweight with a very high number of oocytes following IVF: An analysis of 65 868 singleton live birth outcomes. Hum Reprod. 2015;30(6):1473–80.
  • 12.Dunaif A, Segal KR, Futterweit W, Dobrjansky A.Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165–74.
  • 13.Georgopoulos NA, Saltamavros AD, Vervita V,Karkoulias K, Adonakis G, Decavalas G, et al. Basal metabolic rate is decreased in women with polycystic ovary syndrome and biochemical hyperandrogenemia and is associated with insulin resistance. Fertil Steril. 2009;92(1):250–5.
  • 14.Fauser BCJM, Tarlatzis, Fauser, Chang, Aziz, Legro,et al. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan 1;19(1):41–7.
  • 15.Palomba S, Russo T, Falbo A, Di Cello A, AmendolaG, Mazza R, et al. Decidual endovascular trophoblast invasion in women with polycystic ovary syndrome: An experimental case-control study. J Clin Endocrinol Metab. 2012;97(7):2441–9.
  • 16.Seppälä M, Taylor RN, Koistinen H, Koistinen R,Milgrom E. Glycodelin: A major lipocalin protein of the reproductive axis with various actions in cell recognition and differentiation. Endocr Rev. 2002;23(4):401–30.
  • 17.Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM,Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92.
  • 18.Solomon CG, Hu FB, Dunaif A, Rich-Edwards J,Willett WC, Hunter DJ, et al. Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. Jama. 2001;286(19):2421–6.
  • 19.Adams J, Dwpolson D, Franks S. Prevalence ofpolycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed). 1986;293(6543):355–9.
  • 20.Bhattacharya SM. Polycystic ovary syndrome andabnormalities in glucose tolerance. Int J Gynecol Obstet. 2009;105(1):29–31.
  • 21.Bakeer E, Radwan R, El Mandoury A, El Rahman AA,Gad M, El Maksoud SA. Anti-Müllerian Hormone as a Diagnostic Marker in Egyptian Infertile Polycystic Ovary Syndrome Females: Correlations with Vitamin D, Total Testosterone, Dyslipidemia, and Anthropometric Parameters. J Med Biochem. 2018;37(4):448–55.
  • 22.Ganie MA, Hassan S, Nisar S, Shamas N, Rashid A,Ahmed I, et al. High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2014;30(11):781–4.
  • 23. Liu W, Li S, Lou X, Li D, Wang F, Zhang Z. Assessmentof neutrophil to lymphocyte ratio, C-reactive protein, mean platelet volume in obese, and nonobese patients with polycystic ovary syndrome. Med (United States). 2022;101(29):E29678.
  • 24.Mazibrada I, Djukić T, Perović S, Plješa-ErcegovacM, Plavšić L, Bojanin D, et al. The association ofhs-CRP and fibrinogen with anthropometric and lipid parameters in non-obese adolescent girls with polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2018;31(11):1213–20.
  • 25.Karoli R, Fatima J, Siddiqi Z, Vatsal P, Sultania A,Maini S. Study of early atherosclerotic markers in women with polycystic ovary syndrome. Indian J Endocrinol Metab. 2012;16(6):1004.
  • 26.Orvieto R, Fisch N, Yulzari-Roll V, La Marca A.Ovarian androgens but not estrogens correlate with the degree of systemic inflammation observed during controlled ovarian hyperstimulation. Gynecol Endocrinol. 2005;21(3):170–3.
  • 27.Kahyaoglu S, Yumuşak OH, Ozyer S, Pekcan MK, ErelM, Cicek MN, et al. Clomiphene citrate treatment cycle outcomes of polycystic ovary syndrome patients based on basal high sensitive C-Reactive protein levels: A cross-sectional study. Int J Fertil Steril. 2017;10(4):320–6.
  • 28.Nawaz S, Lynch MP. Rabbit Uterine Epithelium.1986;
  • 29.Vaskivuo TE, Stenbäck F, Karhumaa P, Risteli J,Dunkel L, Tapanainen JS. Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol. 2000;165(1–2):75–83. 95

EVALUATION OF ENDOMETRIAL Bcl-2 EXPRESSION AND Ki-67 PROLIFERATIVE INDEX IN INFERTILE PATIENTS WITH AND WITHOUT POLYCYSTIC OVARY SYNDROME

Year 2023, , 87 - 95, 31.03.2023

Dilay Karademir , Akın Usta , Eren Altun

https://doi.org/10.7197/cmj.1250217
An Erratum to this article was published on May 8, 2023. http://cmj.cumhuriyet.edu.tr/en/pub/cmj/issue/77213/1294036

Abstract

Objective: In women of reproductive age, polycystic ovary syndrome (PCOS) is the most prevalent cause of infertility. The purpose of this study is to compare the Bcl-2 and Ki-67 values between infertile patients with and without PCOS.
Material and methods: The study included twenty-seven infertile patients diagnosed with PCOS and another twenty-eight infertile patients who did not meet the criteria for PCOS. Smoking, pelvic infection symptoms, endometrial polyps and submucosal myomas during a transvaginal ultrasound, pituitary insufficiency, hyperprolactinemia, congenital adrenal hyperplasia, having had adnexal surgery and having a male factor that will result in infertility are all considered exclusion criteria. All patients' data were collected, including age, the length of their infertility, body mass index (BMI), waist-to-hip ratio (WHR), hirsutism score, blood pressure, total testosterone, triglyceride, total cholesterol, LDL, and HDL values, as well as Homa-IR and Hs-CRP readings. The pathology specialist in the examples evaluated Bcl-2 and Ki-67 levels.
Results: We found that BMI, WHR, total testosterone level, blood pressure, total cholesterol, HOMA-IR, and hs-CRP values were significantly higher in infertile cases with PCOS. We also found that the Ki-67 and Bcl-2 values were higher in endometrial cells in sterile PCOS cases than in the control group.
Conclusions: Ki-67 and Bcl-2 levels rise in PCOS patients, preventing apoptosis, limiting the formation of a suitable endometrial environment, and preventing embryo implantation. PCOS patients may frequently experience infertility and recurrent pregnancy losses. The cause of this problem may be the increased activity of estrogen. The primary treatment for PCOS will depend on further investigation into the variables affecting estrogen synthesis and GnRH release. The care plan should be built around this goal.

Keywords

Apoptosis Bcl-2 Infertility Ki-67 Polycystic Ovary Syndrome

References

  • 1.Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106(1):6–15.
  • 2.Costello MF, Misso ML, Balen A, Boyle J, Devoto L,Garad RM, et al. A brief update on the evidence supporting infertility treatment in polycystic ovary syndrome. Aust New Zeal J Obstet Gynaecol. 2019;59(6):867–73.
  • 3.Al-Obaidi MT, Ali ZH, AL-Saadi WI, AL-Wasiti EAR, Al-Aubaidy H. Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with the polycystic ovarian syndrome. J Clin Pharm Ther. 2019;44(4):618–22.
  • 4.Maliqueo M, Clementi M, Gabler F, Johnson MC,Palomino A, Sir-Petermann T, et al. Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome. Fertil Steril. 2003;80(SUPPL. 2):812–9.
  • 5.Dabadghao P. Polycystic ovary syndrome inadolescents. Best Pract Res Clin Endocrinol Metab. 2019;33(3):101272.
  • 6.Dewailly D, Robin G, Peigne M, Decanter C, Pigny P,Catteau-Jonard S. Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update. 2016;22(6):709–24.
  • 7.Fauser BCJM, Tarlatzis BC, Rebar RW, Legro RS, BalenAH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38.e25.
  • 8.Yazıcı P, ALİZADEHSHARGH S, AKDOĞAN GG.Apopitoz: Düzenleyici Moleküller, Hastalıklarla İlişkisi ve Apopitozu Saptama Yöntemleri. Türkiye Klin Tıp Bilim Derg. 2009;29(6):1677–86.
  • 9.Paulson M, Norstedt G, Sahlin L, Hirschberg AL.Association between prolactin receptor expression and proliferation in the endometrium of obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2020;36(3):226–32.
  • 10.Piltonen TT. Polycystic ovary syndrome:Endometrial markers. Best Pract Res Clin ObstetGynecol. 2016;37(April):66–79.
  • 11.Sunkara SK, La Marca A, Seed PT, Khalaf Y.Increased risk of preterm birth and low birthweight with a very high number of oocytes following IVF: An analysis of 65 868 singleton live birth outcomes. Hum Reprod. 2015;30(6):1473–80.
  • 12.Dunaif A, Segal KR, Futterweit W, Dobrjansky A.Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165–74.
  • 13.Georgopoulos NA, Saltamavros AD, Vervita V,Karkoulias K, Adonakis G, Decavalas G, et al. Basal metabolic rate is decreased in women with polycystic ovary syndrome and biochemical hyperandrogenemia and is associated with insulin resistance. Fertil Steril. 2009;92(1):250–5.
  • 14.Fauser BCJM, Tarlatzis, Fauser, Chang, Aziz, Legro,et al. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan 1;19(1):41–7.
  • 15.Palomba S, Russo T, Falbo A, Di Cello A, AmendolaG, Mazza R, et al. Decidual endovascular trophoblast invasion in women with polycystic ovary syndrome: An experimental case-control study. J Clin Endocrinol Metab. 2012;97(7):2441–9.
  • 16.Seppälä M, Taylor RN, Koistinen H, Koistinen R,Milgrom E. Glycodelin: A major lipocalin protein of the reproductive axis with various actions in cell recognition and differentiation. Endocr Rev. 2002;23(4):401–30.
  • 17.Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM,Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92.
  • 18.Solomon CG, Hu FB, Dunaif A, Rich-Edwards J,Willett WC, Hunter DJ, et al. Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. Jama. 2001;286(19):2421–6.
  • 19.Adams J, Dwpolson D, Franks S. Prevalence ofpolycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed). 1986;293(6543):355–9.
  • 20.Bhattacharya SM. Polycystic ovary syndrome andabnormalities in glucose tolerance. Int J Gynecol Obstet. 2009;105(1):29–31.
  • 21.Bakeer E, Radwan R, El Mandoury A, El Rahman AA,Gad M, El Maksoud SA. Anti-Müllerian Hormone as a Diagnostic Marker in Egyptian Infertile Polycystic Ovary Syndrome Females: Correlations with Vitamin D, Total Testosterone, Dyslipidemia, and Anthropometric Parameters. J Med Biochem. 2018;37(4):448–55.
  • 22.Ganie MA, Hassan S, Nisar S, Shamas N, Rashid A,Ahmed I, et al. High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2014;30(11):781–4.
  • 23. Liu W, Li S, Lou X, Li D, Wang F, Zhang Z. Assessmentof neutrophil to lymphocyte ratio, C-reactive protein, mean platelet volume in obese, and nonobese patients with polycystic ovary syndrome. Med (United States). 2022;101(29):E29678.
  • 24.Mazibrada I, Djukić T, Perović S, Plješa-ErcegovacM, Plavšić L, Bojanin D, et al. The association ofhs-CRP and fibrinogen with anthropometric and lipid parameters in non-obese adolescent girls with polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2018;31(11):1213–20.
  • 25.Karoli R, Fatima J, Siddiqi Z, Vatsal P, Sultania A,Maini S. Study of early atherosclerotic markers in women with polycystic ovary syndrome. Indian J Endocrinol Metab. 2012;16(6):1004.
  • 26.Orvieto R, Fisch N, Yulzari-Roll V, La Marca A.Ovarian androgens but not estrogens correlate with the degree of systemic inflammation observed during controlled ovarian hyperstimulation. Gynecol Endocrinol. 2005;21(3):170–3.
  • 27.Kahyaoglu S, Yumuşak OH, Ozyer S, Pekcan MK, ErelM, Cicek MN, et al. Clomiphene citrate treatment cycle outcomes of polycystic ovary syndrome patients based on basal high sensitive C-Reactive protein levels: A cross-sectional study. Int J Fertil Steril. 2017;10(4):320–6.
  • 28.Nawaz S, Lynch MP. Rabbit Uterine Epithelium.1986;
  • 29.Vaskivuo TE, Stenbäck F, Karhumaa P, Risteli J,Dunkel L, Tapanainen JS. Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol. 2000;165(1–2):75–83. 95
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Surgical Science Research Articles
Authors

Dilay Karademir 0000-0002-9813-4255

Akın Usta 0000-0001-8973-4374

Eren Altun 0000-0001-9110-8364

Publication Date March 31, 2023
Acceptance Date March 22, 2023
Published in Issue Year 2023

Cite

AMA Karademir D, Usta A, Altun E. EVALUATION OF ENDOMETRIAL Bcl-2 EXPRESSION AND Ki-67 PROLIFERATIVE INDEX IN INFERTILE PATIENTS WITH AND WITHOUT POLYCYSTIC OVARY SYNDROME. CMJ. March 2023;45(1):87-95. doi:10.7197/cmj.1250217