Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle

  • Koo, Hwa Seon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Cha, Sun Hwa (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Kim, Hye Ok (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Song, In Ok (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Min, Eung Gi (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Yang, Kwang Moon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Park, Chan Woo (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine)
  • Received : 2015.09.24
  • Accepted : 2015.11.11
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. Methods: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. Results: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group ($17.3{\pm}7.2$ vs. $11.0{\pm}7.2$; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Conclusion: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.

Keywords

References

  1. Moon YS, Tsang BK, Simpson C, Armstrong DT. 17 beta-Estradiol biosynthesis in cultured granulosa and thecal cells of human ovarian follicles: stimulation by follicle-stimulating hormone. J Clin Endocrinol Metab 1978;47:263-7. https://doi.org/10.1210/jcem-47-2-263
  2. Venetis CA, Kolibianakis EM, Papanikolaou E, Bontis J, Devroey P, Tarlatzis BC. Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis. Hum Reprod Update 2007;13:343-55. https://doi.org/10.1093/humupd/dmm007
  3. Simon C, Cano F, Valbuena D, Remohi J, Pellicer A. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod 1995;10:2432-7. https://doi.org/10.1093/oxfordjournals.humrep.a136313
  4. Yu Ng EH, Yeung WS, Yee Lan Lau E, So WW, Ho PC. High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles. Hum Reprod 2000;15:250-5. https://doi.org/10.1093/humrep/15.2.250
  5. Orvieto R, Meltzer S, Rabinson J, Zohav E, Anteby EY, Nahum R. GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of endometrial receptivity. Fertil Steril 2008;90:1294-6. https://doi.org/10.1016/j.fertnstert.2007.10.022
  6. Bosch E, Labarta E, Crespo J, Simon C, Remohi J, Jenkins J, et al. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod 2010;25:2092-100. https://doi.org/10.1093/humrep/deq125
  7. Hohmann FP, Macklon NS, Fauser BC. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab 2003;88:166-73. https://doi.org/10.1210/jc.2002-020788
  8. Weghofer A, Margreiter M, Bassim S, Sevelda U, Beilhack E, Feichtinger W. Minimal stimulation using recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist in women of advanced age. Fertil Steril 2004;81:1002-6. https://doi.org/10.1016/j.fertnstert.2003.09.050
  9. Ragni G, Vegetti W, Riccaboni A, Engl B, Brigante C, Crosignani PG. Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome. Hum Reprod 2005;20:2421-5. https://doi.org/10.1093/humrep/dei074
  10. de Ziegler D, Bijaoui G, Chapron C. Pre-hCG elevation of plasma progesterone: good, bad or otherwise. Hum Reprod Update 2008;14:393. https://doi.org/10.1093/humupd/dmn020
  11. Fleming R. Progesterone elevation on the day of hCG: methodological issues. Hum Reprod Update 2008;14:391-2. https://doi.org/10.1093/humupd/dmn019
  12. Kyrou D, Kolibianakis EM, Fatemi HM, Camus M, Tournaye H, Tarlatzis BC, et al. 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;96:884-8. https://doi.org/10.1016/j.fertnstert.2011.07.1101
  13. Kyrou D, Al-Azemi M, Papanikolaou EG, Donoso P, Tziomalos K, Devroey P, et al. 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;162:165-8. https://doi.org/10.1016/j.ejogrb.2012.02.025
  14. Bosch E, Valencia I, Escudero E, Crespo J, Simon C, Remohi J, et al. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril 2003;80:1444-9. https://doi.org/10.1016/j.fertnstert.2003.07.002
  15. Fleming R, Jenkins J. The source and implications of progesterone rise during the follicular phase of assisted reproduction cycles. Reprod Biomed Online 2010;21:446-9. https://doi.org/10.1016/j.rbmo.2010.05.018
  16. Prien SD, Canez MS, Messer RH. Increases in progesterone after human chorionic gonadotropin administration may predict cycle outcome in patients undergoing in vitro fertilization-embryo transfer. Fertil Steril 1994;62:1066-8. https://doi.org/10.1016/S0015-0282(16)57075-7
  17. Penzias AS, Shamma FN, Gutmann JN, Jones EE, DeCherney AH, Lavy G. Nafarelin versus leuprolide in ovulation induction for in vitro fertilization: a randomized clinical trial. Obstet Gynecol 1992;79:739-42.
  18. Doldi N, Marsiglio E, Destefani A, Gessi A, Merati G, Ferrari A. Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome. Hum Reprod 1999;14:601-5. https://doi.org/10.1093/humrep/14.3.601
  19. Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011;26:1768-74. https://doi.org/10.1093/humrep/der106
  20. Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril 2012;97:1321-7.e1-4. https://doi.org/10.1016/j.fertnstert.2012.03.014
  21. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update 2003;9:515-22. https://doi.org/10.1093/humupd/dmg045
  22. Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase. Fertil Steril 1997;67:521-6. https://doi.org/10.1016/S0015-0282(97)80080-5
  23. Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril 2002;78:1025-9. https://doi.org/10.1016/S0015-0282(02)03323-X
  24. Kolibianakis EM, Devroey P. The luteal phase after ovarian stimulation. Reprod Biomed Online 2002;5 Suppl 1:26-35.
  25. Papanikolaou EG, Bourgain C, Kolibianakis E, Tournaye H, Devroey P. Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes. Hum Reprod 2005;20:1541-7. https://doi.org/10.1093/humrep/deh793
  26. Kreitmann B, Bugat R, Bayard F. Estrogen and progestin regulation of the progesterone receptor concentration in human endometrium. J Clin Endocrinol Metab 1979;49:926-9. https://doi.org/10.1210/jcem-49-6-926

Cited by

  1. Fresh embryos versus freeze-all embryos - transfer strategies: Nuances of a meta-analysis vol.21, pp.3, 2015, https://doi.org/10.5935/1518-0557.20170048
  2. Serial Evaluation of Endometrial Blood Flow for Prediction of Pregnancy Outcomes in Patients Who Underwent Controlled Ovarian Hyperstimulation and In Vitro Fertilization and Embryo Transfer : Study of vol.37, pp.4, 2015, https://doi.org/10.1002/jum.14418
  3. Follicle growth and endocrine dynamics in women with spontaneous luteinized unruptured follicles versus ovulation vol.33, pp.6, 2015, https://doi.org/10.1093/humrep/dey082
  4. Progesterone level significance in agonist versus antagonist protocols vol.23, pp.2, 2018, https://doi.org/10.1016/j.mefs.2017.09.010
  5. Adverse effect of prematurely elevated progesterone in in vitro fertilization cycles: a literature review vol.99, pp.1, 2015, https://doi.org/10.1093/biolre/ioy082
  6. The curious case of premature luteinization vol.35, pp.10, 2015, https://doi.org/10.1007/s10815-018-1264-8
  7. Progesterone elevation on the day of hCG trigger has detrimental effect on live birth rate in low and intermediate ovarian responders, but not in high responders vol.9, pp.None, 2015, https://doi.org/10.1038/s41598-019-41499-1
  8. Impact of Serum Progesterone Levels in GnRH Antagonist Assisted Reproduction Cycles on Pregnancy Outcomes: A Prospective Cohort Study vol.9, pp.1, 2019, https://doi.org/10.4236/ojog.2019.91005
  9. Mitochondrial DNA in Fresh versus Frozen Embryo Culture Media of Polycystic Ovarian Syndrome Patients Undergoing Invitro Fertilization: A Possible Predictive Marker of a Successful Pregnancy vol.14, pp.None, 2015, https://doi.org/10.2147/pgpm.s284064
  10. Pre-ovulatory hormones on day of human chorionic gonadotropin trigger and assisted reproductive technique outcomes in different ovarian response groups vol.14, pp.4, 2015, https://doi.org/10.4103/jhrs.jhrs_91_21