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Antagonist/Agonist İn Vitro Fertilizasyon Sikluslarında Hcg Günü Serum Progesteron Konsantrasyonu ile Oosit Maturasyonu, Embriyo Kalitesi ve İmplantasyon Başarısı Arasındaki İlişkinin İncelenmesi

Year 2021, Volume: 11 Issue: 3, 516 - 522, 22.09.2021
https://doi.org/10.31832/smj.939080

Abstract

ÖZ
Amaç: Kontrollü overyan hiperstimülasyon (KOH) tedavilerinde, Prematür Lüteinizasyon (PL) ve gebelik sonucunu saptamak için net bir progesteron (P) eşik değeri yoktur. Her kliniğin PL için P eşik değeri belirlemesi önerilmektedir. Çalışmamızda kliniğimizdeki PL nedeni olan P eşik değerini elde etmeyi amaçladık.
Gereç ve Yöntemler: Tüp bebek merkezimize in vitro fertilizasyon (IVF) tedavisi için gelen 119 çiftimize ait tedavi protokolleri retrospektif olarak değerlendirildi. Human Koryonik Gonadotropini (HCG) günü serum P seviyelerinin 1,2 ng/mL konsantrasyonların üzerinde ve altındaki değerlerde olmasının IVF- İntrasitoplazmik Sperm Enjeksiyonu (ICSI) siklus parametrelerine etkisi incelendi. Parametre kriterleri olarak toplam oosit sayısı, metafaz II (M II) oosit sayısı, fertilize oosit sayısı, transfer günü grade 1 embriyo sayıları ve transfer sonrası saptanan HCG pozitiflikleri incelendi.
Bulgular: Serum P eşik seviyesi 1,2 ng/mL sınır olarak alındığında PL görülme oranı %28,6 di. Çalışma grubunun genel tedavi çıktıları incelendiğinde agonist (n:42) veya antagonist (n:77) protokolleri arasında, M II oosit sayısı ve endometriyum kalınlığı antagonist grupta agonist gruba kıyasla istatistiksel açıdan anlamlı olarak yüksek bulundu (sırasıyla; p=0.038; p=0,017). Siklus tipi dahil edilmeden P eşik değeri 1,2 ng/mL olarak kabul edildiğinde bu değerin altında(n:85) ve üstünde(n:34) bulunan sikluslar karşılaştırıldı. HCG günü Estardiol (E2) ve P değerleri ile fertilize oosit sayısı, Grade1 embriyo sayıları arasında istatistiksel olarak anlamlı farklar görüldü. (sırasıyla p=0,041; p=0,000; p=0,041 ve p= 0,003).
Sonuç: Serum P eşiği 1,2 ng / mL alındığında, bu değerin altındaki ve üstündeki P değerlerinde gruplar karşılaştırıldığında, Serum P eşiği 1,2 ng / mL altında olan grup lehine fertilize oosit sayısı, transfer günü Grade1 embriyo sayıları ile E2 hormon düzeyleri arasında istatistiksel olarak anlamlı farklar görüldü. Bu bulgulara rağmen iki grubun gebelik oranları yönünden farklılık bulunamadı. Konu hakkında daha etkin sonuçlara ulaşmak için daha fazla hasta sayısıyla yapılan çalışma verilerine ihtiyaç duyulmaktadır.

Supporting Institution

HERHAN GİR DESTEKLEYEN KURUM BUUNMAMAKTADIR

References

  • 1. Bosch E, Valencia A., , Escudero E., Crespo J, Simo´n C, Remohı J, .,et al Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertility and sterility 2003;VOL. 80.
  • 2. Hofmann GE, Bentzien F, Bergh PA, Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality. Fertility and Sterility 1993;60(4):675-679.
  • 3. .Legro RSS., Paulson RJ,.Stanczyk FZ.,Sauer MV. Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization. Human Reproduction 1993;vol.8:1506-1511.
  • 4. Ubaldi F. , Wisanto A., Joris H., Schiettecatte J.,.Derde MP., Borkham E et al. Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone. Human Reproduction 1995;vo! 10 .3091-3096.
  • 5. Fanchin R, Ziegler D, Taieb J, Hazout A, Frydman R. Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer Fertility and Sterility 1993;59(5):1090-1094.
  • 6. Givens CR, Schriock ED, Dandekar PV, Martin MC. Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles. Fertility and Sterility 1994;62(5):1011-1017.
  • 7. Patton PE, Lim JY, Hickok LR, Kettel LM, Larson JM, Pau KY. Precision of progesterone measurements with the use of automated immunoassay analyzers and the impact on clinical decisions for in vitro fertilization. Fertil Steril 2014;101(6):1629-1636.
  • 8. Bourgain C., Ubaldi F..,Tavaniotou A., Smitz J, Andre C., Steirteghem V, et al. Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome. Fertility And Sterility 2002;VOL. 78, NO. 2.
  • 9. Alan L. Schneyer TF, Janis F, Corrine K., Judith A., Geralyn M.et al Dynamic Changes in the Intrafollicular Inhibin/Activin/ Follistatin Axis during Human Follicular Development: Relationship to Circulating Hormone Concentrations*. The Journal of Clinical Endocrinology & Metabolism 2000;Vol. 85,.
  • 10. Kyrou D, Al-Azemi M, Papanikolaou EG.. The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles. Eur J Obstet Gynecol Reprod Biol 2012;162(2):165-168.
  • 11. Park JH, Jee BC, Kim SH. Factors influencing serum progesterone level on triggering day in stimulated in vitro fertilization cycles. Clin Exp Reprod Med 2015;42(2):67-71.
  • 12. Papaleo E, Corti L, Vanni VS.. Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles. Arch Gynecol Obstet 2014;290(1):169-176.
  • 13. Erdem M, Mutlu MF, Erdem A, Mutlu I, Guler I, Oktem M. The predictive value of early follicular progesteron on preovulatuary progesteron rise in IVF cycles with GNRH antagonist protocol. Fertility and Sterility 2015;104(3).
  • 14. Hamdine O, Macklon NS, Eijkemans MJ.. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril 2014;102(2):448-454 e441.
  • 15. Venetis CA, Kolibianakis EM, Bosdou JK. Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles. Hum Reprod 2016;31(8):1859-1865.
  • 16. Kyrou D, Kolibianakis EM, Fatemi HM.. High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2011;96(4):884-888.
  • 17. Hugues JN, Masse-Laroche E, Reboul-Marty J, Boiko O, Meynant C, Cedrin-Durnerin I. Impact of endogenous luteinizing hormone serum levels on progesterone elevation on the day of human chorionic gonadotropin administration. Fertil Steril 2011;96(3):600-604.
  • 18. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril 2010;93(2):636-641.
  • 19. Healy MW, Patounakis G, Connell MT. Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? Fertil Steril 2016;105(1):93-99 e91.
  • 20. Yang S, Pang T, Li R. The individualized choice of embryo transfer timing for patients with elevated serum progesterone level on the HCG day in IVF/ICSI cycles: a prospective randomized clinical study. Gynecol Endocrinol 2015;31(5):355-358.
  • 21. Racca A, Santos-Ribeiro S, De Munck N. Impact of late-follicular phase elevated serum progesterone on cumulative live birth rates: is there a deleterious effect on embryo quality? Hum Reprod 2018;33(5):860-868.
  • 22.Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update 2013;19(5):433-457.
  • 23. Smitz J, Ron-El R, Tarlatzis BC. The use of gonadotrophin releasing hormone agonists for in vitro fertilization and other assisted procreation techniques: Experience from three centres. Human Reproduction 1992;7(suppl_1):49-66.
  • 24. Choi MH, Cha SH, Park CW.. The effectiveness of earlier oocyte retrieval in the case of a premature luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer cycles. Clin Exp Reprod Med 2013;40(2):90-94.
  • 25. Peng C, Guo Z, Long X, Lu G. Progesterone levels on the hCG day and outcomes in vitro fertilization in women with polycystic ovary syndrome. J Assist Reprod Genet 2012;29(7):603-607.
  • 26. Elnashar A. Progesterone rise on the day of HCG administration (premature luteinization) in IVF: An overdue update. J Assist Reprod Genet 2010;27:149-155.
  • 27. Lai TH, Lee FK, Lin TK. An increased serum progesterone-to-estradiol ratio on the day of human chorionic gonadotropin administration does not have a negative impact on clinical pregnancy rate in women with normal ovarian reserve treated with a long gonadotropin releasing hormone agonist protocol. Fertil Steril 2009;92(2):508-514.
  • 28. Segal S, Glatstein I, McShane P, Hotamisligil S, Ezcurra D, Carson R. Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome. Fertil Steril 2009;91(5):1755-1759.
  • 29. Melo MA, Meseguer M, Garrido N, Bosch E, Pellicer A, Remohí J. The significance of premature luteinization in an oocyte-donation programme. Hum Reprod 2006;21(6):1503-1507.
  • 30. Santos-Ribeiro S, Racca A, Roelens C, De Munck N, Mackens S, Drakopoulos P, et al. Evaluating the benefit of measuring serum progesterone prior to the administration of HCG: effect of the duration of late-follicular elevated progesterone following ovarian stimulation on fresh embryo transfer live birth rates. Reprod BioMed Online 2019;38:647–54
  • 31. Golbasi H, Ince O, Golbasi C, Ozer M, Demir M, Yilmaz B. Effect of progesterone/estradiol ratio on pregnancy outcome of patients with high trigger-day progesterone levels undergoing gonadotropin-releasing hormone antagonist intracytoplasmic sperm injection cycles: a retrospective cohort study. J Obstet Gynaecol 2019;39:157–63.
  • 32. Kaponis A, Chronopoulou E, Decavalas G. The curious case of premature luteinization. J. Assist. Reprod. Genet 2018; 35: 1723–1740
  • 33. Merviel P, Bouée S, Jacamon AS, Chabaud JJ, Le Martelot MT, Roche S, et al.. Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations. BMC Pregnancy Childbirth 2021 May 6;21(1):363. doi: 10.1186/s12884-021-03832-3. PMID: 3395788

Antagonıst/Agonıst In Vıtro Fertılızatıon Cycles Investıgatıon of The Relatıonshıp Between Hcg Day Serum Progesterone Concentratıon and Oocyte Maturatıon, Embryo Qualıty and Implantatıon Success

Year 2021, Volume: 11 Issue: 3, 516 - 522, 22.09.2021
https://doi.org/10.31832/smj.939080

Abstract

Objective: There is no clear progesterone (P) threshold value to detect Premature Luteinization (PL) and pregnancy outcome in controlled ovarian hyperstimulation (COH) treatments. Therefore, clinics are advised to set their own P thresholds for PL. In our study, we aimed to obtain the P threshold value, which is the cause of PL in our clinic.

Material and Methods: Treatment protocols of 119 couples who came to our assisted reproductive techniques center for in vitro fertilization (IVF) treatment were evaluated retrospectively. In our study, the effect of serum P levels above and below the 1.2 ng/mL threshold value on the day of Human Chorionic Gonadotropin (HCG) on IVF- Intracytoplasmic Sperm Injection (ICSI) cycle parameters were investigated. During the evaluation, the total number of oocytes, the number of metaphase II (M II) oocytes, the number of fertilized oocytes, the number of grade 1 embryos on the day of transfer and the HCG positivity values detected after the transfer were examined.

Results: In case of serum P threshold value of 1.2 ng/mL, the incidence of PL was found to be 28.6%. When the treatment results of the study group were examined, M II oocyte count and endometrial thickness were found to be statistically significantly higher in the antagonist group in terms of using agonist (n:42) or antagonist (n:77) protocol (respectively; p=0.038; p=0.017). Regardless of the protocol of cycle, patients with a P threshold value (1.2 ng/mL) below (n:85) and above (n:34) were compared. In this evaluation, there were statistically significant differences between Estradiol (E2) and P values on the HCG day, and the number of fertilized oocytes and Grade1 embryos. (p=0.041; p=0.000; p=0.041 and p= 0.003), respectively.

Conclusion: When the serum P threshold value was taken as 1.2 ng / mL, statistically significant differences were observed between the number of fertilized oocytes, the number of Grade1 embryos on the day of transfer and E2 hormone levels in favor of the patient group below this value. However, no difference was found between the two groups in terms of pregnancy rates. In order to reach more effective results on the subject, study data with a larger number of patients is needed.

References

  • 1. Bosch E, Valencia A., , Escudero E., Crespo J, Simo´n C, Remohı J, .,et al Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertility and sterility 2003;VOL. 80.
  • 2. Hofmann GE, Bentzien F, Bergh PA, Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality. Fertility and Sterility 1993;60(4):675-679.
  • 3. .Legro RSS., Paulson RJ,.Stanczyk FZ.,Sauer MV. Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization. Human Reproduction 1993;vol.8:1506-1511.
  • 4. Ubaldi F. , Wisanto A., Joris H., Schiettecatte J.,.Derde MP., Borkham E et al. Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone. Human Reproduction 1995;vo! 10 .3091-3096.
  • 5. Fanchin R, Ziegler D, Taieb J, Hazout A, Frydman R. Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer Fertility and Sterility 1993;59(5):1090-1094.
  • 6. Givens CR, Schriock ED, Dandekar PV, Martin MC. Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles. Fertility and Sterility 1994;62(5):1011-1017.
  • 7. Patton PE, Lim JY, Hickok LR, Kettel LM, Larson JM, Pau KY. Precision of progesterone measurements with the use of automated immunoassay analyzers and the impact on clinical decisions for in vitro fertilization. Fertil Steril 2014;101(6):1629-1636.
  • 8. Bourgain C., Ubaldi F..,Tavaniotou A., Smitz J, Andre C., Steirteghem V, et al. Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome. Fertility And Sterility 2002;VOL. 78, NO. 2.
  • 9. Alan L. Schneyer TF, Janis F, Corrine K., Judith A., Geralyn M.et al Dynamic Changes in the Intrafollicular Inhibin/Activin/ Follistatin Axis during Human Follicular Development: Relationship to Circulating Hormone Concentrations*. The Journal of Clinical Endocrinology & Metabolism 2000;Vol. 85,.
  • 10. Kyrou D, Al-Azemi M, Papanikolaou EG.. The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles. Eur J Obstet Gynecol Reprod Biol 2012;162(2):165-168.
  • 11. Park JH, Jee BC, Kim SH. Factors influencing serum progesterone level on triggering day in stimulated in vitro fertilization cycles. Clin Exp Reprod Med 2015;42(2):67-71.
  • 12. Papaleo E, Corti L, Vanni VS.. Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles. Arch Gynecol Obstet 2014;290(1):169-176.
  • 13. Erdem M, Mutlu MF, Erdem A, Mutlu I, Guler I, Oktem M. The predictive value of early follicular progesteron on preovulatuary progesteron rise in IVF cycles with GNRH antagonist protocol. Fertility and Sterility 2015;104(3).
  • 14. Hamdine O, Macklon NS, Eijkemans MJ.. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril 2014;102(2):448-454 e441.
  • 15. Venetis CA, Kolibianakis EM, Bosdou JK. Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles. Hum Reprod 2016;31(8):1859-1865.
  • 16. Kyrou D, Kolibianakis EM, Fatemi HM.. High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2011;96(4):884-888.
  • 17. Hugues JN, Masse-Laroche E, Reboul-Marty J, Boiko O, Meynant C, Cedrin-Durnerin I. Impact of endogenous luteinizing hormone serum levels on progesterone elevation on the day of human chorionic gonadotropin administration. Fertil Steril 2011;96(3):600-604.
  • 18. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril 2010;93(2):636-641.
  • 19. Healy MW, Patounakis G, Connell MT. Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? Fertil Steril 2016;105(1):93-99 e91.
  • 20. Yang S, Pang T, Li R. The individualized choice of embryo transfer timing for patients with elevated serum progesterone level on the HCG day in IVF/ICSI cycles: a prospective randomized clinical study. Gynecol Endocrinol 2015;31(5):355-358.
  • 21. Racca A, Santos-Ribeiro S, De Munck N. Impact of late-follicular phase elevated serum progesterone on cumulative live birth rates: is there a deleterious effect on embryo quality? Hum Reprod 2018;33(5):860-868.
  • 22.Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update 2013;19(5):433-457.
  • 23. Smitz J, Ron-El R, Tarlatzis BC. The use of gonadotrophin releasing hormone agonists for in vitro fertilization and other assisted procreation techniques: Experience from three centres. Human Reproduction 1992;7(suppl_1):49-66.
  • 24. Choi MH, Cha SH, Park CW.. The effectiveness of earlier oocyte retrieval in the case of a premature luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer cycles. Clin Exp Reprod Med 2013;40(2):90-94.
  • 25. Peng C, Guo Z, Long X, Lu G. Progesterone levels on the hCG day and outcomes in vitro fertilization in women with polycystic ovary syndrome. J Assist Reprod Genet 2012;29(7):603-607.
  • 26. Elnashar A. Progesterone rise on the day of HCG administration (premature luteinization) in IVF: An overdue update. J Assist Reprod Genet 2010;27:149-155.
  • 27. Lai TH, Lee FK, Lin TK. An increased serum progesterone-to-estradiol ratio on the day of human chorionic gonadotropin administration does not have a negative impact on clinical pregnancy rate in women with normal ovarian reserve treated with a long gonadotropin releasing hormone agonist protocol. Fertil Steril 2009;92(2):508-514.
  • 28. Segal S, Glatstein I, McShane P, Hotamisligil S, Ezcurra D, Carson R. Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome. Fertil Steril 2009;91(5):1755-1759.
  • 29. Melo MA, Meseguer M, Garrido N, Bosch E, Pellicer A, Remohí J. The significance of premature luteinization in an oocyte-donation programme. Hum Reprod 2006;21(6):1503-1507.
  • 30. Santos-Ribeiro S, Racca A, Roelens C, De Munck N, Mackens S, Drakopoulos P, et al. Evaluating the benefit of measuring serum progesterone prior to the administration of HCG: effect of the duration of late-follicular elevated progesterone following ovarian stimulation on fresh embryo transfer live birth rates. Reprod BioMed Online 2019;38:647–54
  • 31. Golbasi H, Ince O, Golbasi C, Ozer M, Demir M, Yilmaz B. Effect of progesterone/estradiol ratio on pregnancy outcome of patients with high trigger-day progesterone levels undergoing gonadotropin-releasing hormone antagonist intracytoplasmic sperm injection cycles: a retrospective cohort study. J Obstet Gynaecol 2019;39:157–63.
  • 32. Kaponis A, Chronopoulou E, Decavalas G. The curious case of premature luteinization. J. Assist. Reprod. Genet 2018; 35: 1723–1740
  • 33. Merviel P, Bouée S, Jacamon AS, Chabaud JJ, Le Martelot MT, Roche S, et al.. Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations. BMC Pregnancy Childbirth 2021 May 6;21(1):363. doi: 10.1186/s12884-021-03832-3. PMID: 3395788
There are 33 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Özcan Budak 0000-0002-2617-3175

Songül Doğanay 0000-0002-1730-1331

Seda Özkuler 0000-0001-5585-0289

Nermin Akdemir 0000-0002-9129-2103

Nureddin Cengiz This is me 0000-0002-2486-5901

Serhan Cevrioğlu 0000-0002-3810-6519

Publication Date September 22, 2021
Submission Date May 19, 2021
Published in Issue Year 2021 Volume: 11 Issue: 3

Cite

AMA Budak Ö, Doğanay S, Özkuler S, Akdemir N, Cengiz N, Cevrioğlu S. Antagonist/Agonist İn Vitro Fertilizasyon Sikluslarında Hcg Günü Serum Progesteron Konsantrasyonu ile Oosit Maturasyonu, Embriyo Kalitesi ve İmplantasyon Başarısı Arasındaki İlişkinin İncelenmesi. Sakarya Tıp Dergisi. September 2021;11(3):516-522. doi:10.31832/smj.939080

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