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Is it the egg or the endometrium? Elevated progesterone on day of trigger is not associated with embryo ploidy nor decreased success rates in subsequent embryo transfer cycles

  • Assisted Reproduction Technologies
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Abstract

Purpose

The purpose of our study was to determine if progesterone (P4) values on day of trigger affect certain cycle outcome parameters, ploidy status of embryos, as well as pregnancy outcomes in the subsequent first frozen embryo transfer cycle.

Methods

Two hundred thirty-eight patients undergoing pre-gestational screening and freeze all protocol at our fertility center from 2013 to 2014 were included. Excluded patients were those whom had cancelled cycles prior to egg retrieval as well as cycles utilizing donor eggs. Once patients were identified as eligible for this study, frozen serum from the day of trigger was identified and analyzed using the Siemens Immulite 2000. Number of eggs retrieved, number of available embryos for biopsy, and number of euploid/aneuploid embryos were analyzed. The first frozen embryo transfer cycle was linked to the initial egg retrieval and outcomes including pregnancy rates, and live birth/ongoing pregnancy rates were calculated and analyzed. A discriminatory P4 value of 1.5 ng/ml was set. Group A had P4 values of less than 1.5 ng/ml and group B had P4 values greater than or equal to 1.5 ng/ml. T tests and chi-squared tests were used for statistical analysis.

Results

Group A had an average trigger P4 value of 0.87 +/− 0.3 and group B had an average trigger P4 of 2.1 +/− 0.8. Table 1 shows the baseline characteristics of both group A and group B. The only significant difference between the two groups was total gonadotropin dosage (IU) with a p value of 0.02 and estradiol (pg/ml) at trigger, also with a p value of 0.02 (Table 1). Number of eggs retrieved, number of embryos biopsied, number euploid/aneuploid, and non-diagnosis embryos were all non-significant. Chi-square analysis was used to compare pregnancy rates between the two groups after the first frozen embryo transfer cycle. Group A had a pregnancy rate of 72 % and Group B had a pregnancy rate of 66.7 %, which was not significant. Ongoing pregnancy/live birth rates were 65.6 % in group A and 66.67 % in group B, also not significant (Table 2).

Conclusions

P4 values on day of trigger do not affect number of eggs retrieved and number of chromosomally normal embryos available for transfer in a subsequent embryo transfer cycle. Elevated P4 values (≥1.5 ng/ml) also do not affect pregnancy rates or live birth/ongoing pregnancy rates in the first subsequent frozen embryo transfer cycle.

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References

  1. Messinis IE, Templeton A, Baird DT. Endogenous luteinizing hormone surge during superovulation induction with sequential use of clomiphene citrate and pulsatile human menopausal gonadotropin. J Clin Endocrinol Metab. 1985;61(6):1076–80.

    Article  CAS  PubMed  Google Scholar 

  2. Venetis, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60000 cycles. Hum Reprod Update. 2013;19(5):433–57.

    Article  CAS  PubMed  Google Scholar 

  3. Bosch E, Valencia W, 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(6):1444–9.

    Article  PubMed  Google Scholar 

  4. 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(8):2092–100.

    Article  CAS  PubMed  Google Scholar 

  5. Fleming R. Progesterone elevation on the day of hCG: methodological issues. Hum Reprod Update. 2008;14(4):391–2.

    Article  CAS  PubMed  Google Scholar 

  6. Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991;55(3):563–6.

    Article  CAS  PubMed  Google Scholar 

  7. Check JH, Lurie D, Askari HA, Hoover L, Lauer C. The range of subtle rise in serum progesterone levels following controlled ovarian hyperstimulation associated with lower in vitro fertilization pregnancy rates is determined by the source of manufacturer. Eur J Obstet Gynecol Reprod Biol. 1993;52(3):205–9.

    Article  CAS  PubMed  Google Scholar 

  8. Fanchin R, de Ziegler D, Taieb J, Hazout A, Frydman R. Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer. Fertil Steril. 1993;59(5):1090–4.

    Article  CAS  PubMed  Google Scholar 

  9. Shulman A, Ghetler Y, Beyth Y, Ben-Nun I. The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a ‘long protocol’ of gonadotropin releasing hormone analogue and human menopausal gonadotropins. J Assist Reprod Genet. 1996;13(3):207–11.

    Article  CAS  PubMed  Google Scholar 

  10. Fanchin R, Hourvitz A, Olivennes F, Taieb J, Hazout A, Frydman. Premature progesterone elevation spares blastulation but not pregnancy rates in in vitro fertilization with coculture. Fertil Steril. 1997;68(4):648–52.

    Article  CAS  PubMed  Google Scholar 

  11. Kiliçdag E, Haydardedeoglu B, Cok T, Hacivelioglu S, Bagis T. Premature progesterone elevation impairs implantation and live birth rates in GnRH-agonist IVF/ICSI cycles. Arch Gynecol Obstet. 2010;281(4):747–52.

    Article  PubMed  Google Scholar 

  12. Ochsenkuhn R, Arzberger A, von Schönfeldt V, Gallwas J, Rogenhofer N, Crispin A, et al. Subtle progesterone rise on the day of human chorionic gonadotropin administration is associated with lower live birth rates in women undergoing assisted reproductive technology: a retrospective study with 2,555 fresh embryo transfers. Fertil Steril. 2012;98(2):347–54.

    Article  PubMed  Google Scholar 

  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(2):165–8.

    Article  CAS  PubMed  Google Scholar 

  14. Park J, Lee B, Kim S. Factors influencing serum progesterone level on triggering day in stimulated in vitro fertilization cycles. Clin Exp Reprod Med. 2015;42(2):67–71.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hill MJ, Royster IV GD, Healy MW, Richter KS, Levy G, DeCherney AH, et al. Are good patient and embryo characteristics protective against the negative effect of elevated progesterone level on the day of oocyte maturation? Fertil Steril. 2015;103(6):1477–84.

    Article  CAS  PubMed  Google Scholar 

  16. Edelstein MC, Seltman HJ, Cox BJ, Robinson SM, Shaw RA, Muasher SJ. Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome. Fertil Steril. 1990;54(5):853–7.

    Article  CAS  PubMed  Google Scholar 

  17. Check JH, Hourani C, Choe JK, Callan C, Adelson HG. Pregnancy rates in donors versus recipients according to the serum progesterone level at the time of human chorionic gonadotropin in a shared oocyte program. Fertil Steril. 1994;61(2):262–4.

    Article  CAS  PubMed  Google Scholar 

  18. 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. Fertil Steril. 1994;62(5):1011–7.

    Article  CAS  PubMed  Google Scholar 

  19. 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(4):343–55.

    Article  CAS  PubMed  Google Scholar 

  20. Check JH, Wilson C, Choe JK, Amui J, Brasile D. Evidence that high serum progesterone (P) levels on day of human chorionic gonadotropin (hCG) injection have no adverse effect on the embryo itself as determined by pregnancy outcome following embryo transfer using donated eggs. Clin Exp Obstet Gynecol. 2010;37(3):179–80.

    CAS  PubMed  Google Scholar 

  21. Elgindy EA. Progesterone level and progesterone/estradiol ratio on the day of hCG administration: detrimental cutoff levels and new treatment strategy. Fertil Steril. 2011;95(5):1639–44.

    Article  CAS  PubMed  Google Scholar 

  22. Papanikolaou EG, Kolibianakis EM, Pozzobon C, Tank P, Tournaye H, Bourgain C, et al. Progesterone rise on the day of human chorionic gonadotropin administration impairs pregnancy outcome in day 3 single-embryo transfer, while has no effect on day 5 single blastocyst transfer. Fertil Steril. 2009;91(3):949–52.

    Article  CAS  PubMed  Google Scholar 

  23. Legro RS, Ary BA, Paulson RJ, Stanczyk FZ, Sauer M. Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization. Hum Reprod. 1993;8(9):1506–11.

    CAS  PubMed  Google Scholar 

  24. 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(3):601–5.

    Article  CAS  PubMed  Google Scholar 

  25. Nagai T, Ding J, Moor RM. Effect of follicle cells and steroidogenesis on maturation and fertilization in vitro of pig oocytes. J Exp Zool. 1993;266(2):146–51.

    Article  CAS  PubMed  Google Scholar 

  26. Stanger JD, Yovich JL. Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase. Br J Obstet Gynaecol. 1985;92(4):85–93.

    Article  Google Scholar 

  27. Eibschitz I, Belaisch-Allart JC, Frydman R. In vitro fertilization management and results in stimulated cycles with a spontaneous luteinizing hormone discharge. Fertil Steril. 1986;45(2):231–6.

    Article  CAS  PubMed  Google Scholar 

  28. Lujueune B, Degueldre M, Camus M, Vekemans M, Opsomer L, Leroy F. In vitro fertilization and embryo transfer as related to endogenous luteinizing hormone rise or human chorionic gonadotropin administration. Fertil Steril. 1986;45(3):377–83.

    Article  Google Scholar 

  29. Van Vaerenbergh, Fatemi HM, Blockeel C, Van Lommel L, In’t Veld P, Schuit F. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011;22(3):263–71.

    Article  PubMed  Google Scholar 

  30. Wu Z, Li R, Ma Y, Deng B, Zhang X, Meng Y, et al. Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod Biomed Online. 2012;24(5):511–20.

    Article  CAS  PubMed  Google Scholar 

  31. Lahoud R, Kwik M, Ryan J, Al-Jefout M, Foley J, Illingworth. Elevated progesterone in GnRH agonist down regulated in vitro fertilisation (IVFICSI) cycles reduces live birth rates but not embryo quality. Arch Gynecol Obstet. 2012;285(2):535–40.

    Article  CAS  PubMed  Google Scholar 

  32. Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011;95(3):953–8.

    Article  CAS  PubMed  Google Scholar 

  33. Grifo J, Hodes-Wertz B, Hsiao-Ling L, Amperloquio E, Clarke-Williams M, Adler A. Single thawed euploid embryo transfer improves IVF pregnancy, miscarriage, and multiple gestation outcomes and has similar implantation rates as egg donation. J Assist Reprod Genet. 2013;30(2):259–64.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Scott Jr RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697–703.

    Article  PubMed  Google Scholar 

  35. Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013;100(1):100–7.

    Article  PubMed  Google Scholar 

  36. Gardner DK, Lane M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum Reprod Update. 1997;3(4):367–82.

    Article  CAS  PubMed  Google Scholar 

  37. Kofinas J, Blakemore J, McCulloh D, Grifo J. Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet. 2015;32(9):1395–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Azem F, Tal G, Lessing, Malcov M, Ben-Yosef D, Almog B, et al. Does high serum progesterone level on the day of human chorionic gonadotropin administration affect pregnancy rate after intracytoplasmic sperm injection and embryo transfer? Gynecol Endocrinol. 2008;24(7):368–72.

    Article  CAS  PubMed  Google Scholar 

  39. Melo, Meseguer M, Garrido N, Bosch E, Pellicer A, Remohi J. The significance of premature luteinization in an oocyte-donation programme. Hum Reprod. 2006;21(6):1503–7.

    Article  CAS  PubMed  Google Scholar 

  40. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril. 2010;93(2):636–41.

    Article  CAS  PubMed  Google Scholar 

  41. Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, et al. Serum progesterone level effects on the outcome of in vitro. Fertil Steril. 2012;97(6):1321–7.

    Article  CAS  PubMed  Google Scholar 

  42. Huang R, Fang C, Xu S, Yi Y, Liang X. Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles. Fertil Steril. 2012;98(3):664–70.

    Article  CAS  PubMed  Google Scholar 

  43. Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.

    Article  CAS  PubMed  Google Scholar 

  44. Franasiak J, Forman E, Hong K, Werner M, Upham K, Scott RT. Investigating the impact of the timing of blastulation on implantation: active management of embryo-endometrial synchrony increases implantation rates. Fertil Steril. 2013;100(3):S97.

    Article  Google Scholar 

  45. Labarta E, Martinez-Conejero JA, Alama P, Horcajadas JA, Pellicer A, Simon C, et al. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011;26(7):1813–25.

    Article  CAS  PubMed  Google Scholar 

  46. Li R, Qiao J, Wang L, Li L, Zhen X, Liu P, et al. MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration. Reprod Biol Endocrinol. 2011;9:29.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. New York University School of Medicine, 660 First Avenue, New York, NY, 10016, USA

    Jason D. Kofinas, Holly Mehr, Nandita Ganguly, Yelena Biley, Svetlana Bochkovsky, David McCulloh & Jamie Grifo

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  1. Jason D. Kofinas
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  2. Holly Mehr
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  3. Nandita Ganguly
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Correspondence to Jason D. Kofinas.

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Capsule

Our findings indicate that elevated progesterone on trigger day (greater than 1.5 ng/ml) is not associated with poor embryo quality or successful live births in subsequent frozen embryo transfer cycles.

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Kofinas, J.D., Mehr, H., Ganguly, N. et al. Is it the egg or the endometrium? Elevated progesterone on day of trigger is not associated with embryo ploidy nor decreased success rates in subsequent embryo transfer cycles. J Assist Reprod Genet 33, 1169–1174 (2016). https://doi.org/10.1007/s10815-016-0752-y

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  • DOI: https://doi.org/10.1007/s10815-016-0752-y

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