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Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol

  • Charalampos Siristatidis EMAIL logo , Panagiotis Drakopoulos , Paraskevi Vogiatzi , Vasilios Karageorgiou and George Daskalakis
Published/Copyright: May 16, 2018

Abstract

In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous “suspects” of reduced success after assisted reproduction techniques (ART) – the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

Author Statement

  1. Research funding: The authors state no funding involved.

  2. Conflict of interest: The authors declare no conflict of interest.

  3. Informed consent: Informed consent is not applicable.

  4. Ethical approval: The conducted research is not related to either human or animals use.

References

[1] Bosch E, Valencia I, Escudero E, Crespo J, Simón C, Remohí J, et al. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril. 2003;80:1444–9.10.1016/j.fertnstert.2003.07.002Search in Google Scholar PubMed

[2] Lin YJ, Lan KC, Huang FJ, Lin PY, Chiang HJ, Kung FT. Reproducibility and clinical significance of pre-ovulatory serum progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration in infertile women undergoing repeated in vitro fertilization cycles. Reprod Biol Endocrinol. 2015;13:41.10.1186/s12958-015-0037-9Search in Google Scholar PubMed

[3] Papaleo E, Corti L, Vanni VS, Pagliardini L, Ottolina J, De Michele F, et al. 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;290:169–76.10.1007/s00404-014-3167-ySearch in Google Scholar PubMed

[4] Papanikolaou EG, Pados G, Grimbizis G, Bili E, Kyriazi L, Polyzos NP, et al. GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of HCG triggering? A randomized prospective study. Hum Reprod. 2012;27:1822–8.10.1093/humrep/des066Search in Google Scholar PubMed

[5] 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;13:343–55.10.1093/humupd/dmm007Search in Google Scholar PubMed

[6] Yovel I, Yaron Y, Amit A, Peyser MR, David MP, Kogosowski A, et al. High progesterone levels adversely affect embryo quality and pregnancy rates in in vitro fertilization and oocyte donation programs. Fertil Steril. 1995;64:128–31.10.1016/S0015-0282(16)57668-7Search in Google Scholar PubMed

[7] Vanni VS, Somigliana E, Reschini M, Pagliardini L, Marotta E, Faulisi S, et al. Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles. PLoS One. 2017;12:e0176482.10.1371/journal.pone.0176482Search in Google Scholar PubMed PubMed Central

[8] 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;19:433–57.10.1093/humupd/dmt014Search in Google Scholar PubMed

[9] Kolibianakis EM, Venetis CA, Bontis J, Tarlatzis BC. Significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH antagonists and gonadotrophins: a systematic review and meta-analysis. Curr Pharm Biotechnol. 2012;13:464–70.10.2174/138920112799361927Search in Google Scholar PubMed

[10] Legro RS, Ary BA, 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. Hum Reprod. 1993;8:1506–11.10.1093/oxfordjournals.humrep.a138288Search in Google Scholar PubMed

[11] Ubaldi F, Albano C, Peukert M, Riethmuller-Winzen H, Camus M, Smitz J, et al. Subtle progesterone rise after the administration of the gonadotrophin-releasing hormone antagonist cetrorelix in intracytoplasmic sperm injection cycles. Hum Reprod. 1996;11:1405–7.10.1093/oxfordjournals.humrep.a019409Search in Google Scholar PubMed

[12] 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;162:165–8.10.1016/j.ejogrb.2012.02.025Search in Google Scholar PubMed

[13] Yding Andersen C, Bungum L, Nyboe Andersen A, Humaidan P. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate. Reprod Biomed Online. 2011;23:187–95.10.1016/j.rbmo.2011.04.003Search in Google Scholar PubMed

[14] Lai TH, Lee FK, Lin TK, Horng SG, Chen SC, Chen YH, et al. 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;92:508–14.10.1016/j.fertnstert.2008.06.036Search in Google Scholar PubMed

[15] Griesinger G, Mannaerts B, Andersen CY, Witjes H, Kolibianakis EM, Gordon K. Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in six trials. Fertil Steril. 2013;100:1622–8.e1-3.10.1016/j.fertnstert.2013.08.045Search in Google Scholar PubMed

[16] Saleh HA, Omran MS, Draz M. Does subtle progesterone rise on the day of HCG affect pregnancy rate in long agonist ICSI cycles? J Assist Reprod Genet. 2009;26:239–42.10.1007/s10815-009-9309-7Search in Google Scholar PubMed PubMed Central

[17] Requena A, Cruz M, Bosch E, Meseguer M, García-Velasco JA. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study. Reprod Biol Endocrinol. 2014;12:69.10.1186/1477-7827-12-69Search in Google Scholar PubMed PubMed Central

[18] Al-Azemi M, Kyrou D, Kolibianakis EM, Humaidan P, Van Vaerenbergh I, Devroey P, Fatemi HM. Elevated progesterone during ovarian stimulation for IVF. Reprod Biomed Online. 2012;24:381–8.10.1016/j.rbmo.2012.01.010Search in Google Scholar PubMed

[19] Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12:731–46.10.1093/humupd/dml004Search in Google Scholar PubMed

[20] Labarta E, Martínez-Conejero JA, Alamá P, Horcajadas JA, Pellicer A, Simón 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;26:1813–25.10.1093/humrep/der126Search in Google Scholar PubMed

[21] Corti L, Papaleo E, Pagliardini L, Rabellotti E, Molgora M, La Marca A, et al. Fresh blastocyst transfer as a clinical approach to overcome the detrimental effect of progesterone elevation at hCG triggering: a strategy in the context of the Italian law. Eur J Obstet Gynecol Reprod Biol. 2013;171:73–7.10.1016/j.ejogrb.2013.08.017Search in Google Scholar PubMed

[22] Hill MJ, Royster 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;103:1477–84.e1-5.10.1016/j.fertnstert.2015.02.038Search in Google Scholar PubMed PubMed Central

[23] 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;96:884–8.10.1016/j.fertnstert.2011.07.1101Search in Google Scholar PubMed

[24] Bosch E, Labarta E, Crespo J, Simón C, Remohí 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;25:2092–100.10.1093/humrep/deq125Search in Google Scholar PubMed

[25] Groenewoud ER, Macklon NS, Cohlen BJ. The effect of elevated progesterone levels before HCG triggering in modified natural cycle frozen-thawed embryo transfer cycles. Reprod Biomed Online. 2017;34:546–54.10.1016/j.rbmo.2017.02.008Search in Google Scholar PubMed

[26] Järvelä IY, Pelkonen S, Uimari O, Mäkikallio K, Puukka K, Ruokonen A, et al. Controlled ovarian hyperstimulation leads to high progesterone and estradiol levels during early pregnancy. Hum Reprod. 2014;29:2393–401.10.1093/humrep/deu223Search in Google Scholar PubMed

[27] Aflatoonian A, Davar R, Hojjat F. Elevated serum progesterone/MII oocyte ratio on the day of human chorionic gonadotropin administration can predict impaired endometrial receptivity. Iran J Reprod Med. 2014;12:427–34.Search in Google Scholar PubMed

[28] Yang S, Pang T, Li R, Yang R, Zhen X, Chen X, et al. 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;31:355–8.10.3109/09513590.2014.995620Search in Google Scholar PubMed

[29] Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28:2728–34.10.1093/humrep/det303Search in Google Scholar PubMed

[30] Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How manyoocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31:370–6.10.1093/humrep/dev316Search in Google Scholar

[31] Fatemi HM, Van Vaerenbergh I. Significance of premature progesterone rise in IVF. Curr Opin Obstet Gynecol. 2015;27:242–8.10.1097/GCO.0000000000000172Search in Google Scholar PubMed

[32] Van Vaerenbergh I, Fatemi HM, Blockeel C, Van Lommel L, In’t Veld P, Schuit F, et al. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011;22:263–71.10.1016/j.rbmo.2010.11.002Search in Google Scholar PubMed

[33] Haouzi D, Bissonnette L, Gala A, Assou S, Entezami F, Perrochia H, et al. Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration. Biomed Res Int. 2014;2014:951937.10.1155/2014/951937Search in Google Scholar PubMed PubMed Central

[34] 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;9:29.10.1186/1477-7827-9-29Search in Google Scholar PubMed PubMed Central

[35] Liu L, Huang J, Li TC, Hong XT, Laird S, Dai YD, et al. The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium. J Reprod Immunol. 2017;121:17–25.10.1016/j.jri.2017.05.001Search in Google Scholar PubMed

[36] Cartwright JE, James-Allan L, Buckley RJ, Wallace AE. The role of decidual NK cells in pregnancies with impaired vascular remodelling. J Reprod Immunol. 2017;119:81–4.10.1016/j.jri.2016.09.002Search in Google Scholar PubMed

[37] Xiong Y, Wang J, Liu L, Chen X, Xu H, Li TC, et al. Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period. Fertil Steril. 2017;108:269–76.e1.10.1016/j.fertnstert.2017.06.004Search in Google Scholar PubMed

[38] 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;42:67–71.10.5653/cerm.2015.42.2.67Search in Google Scholar PubMed PubMed Central

[39] Tsai YR, Huang FJ, Lin PY, Kung FT, Lin YJ, Lin YC, et al. Progesterone elevation on the day of human chorionic gonadotropin administration is not the only factor determining outcomes of in vitro fertilization. Fertil Steril. 2015;103:106–11.10.1016/j.fertnstert.2014.10.019Search in Google Scholar PubMed

[40] Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, et al. 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;31:1859–65.10.1093/humrep/dew141Search in Google Scholar PubMed

[41] 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;91:949–52.10.1016/j.fertnstert.2006.12.064Search in Google Scholar PubMed

[42] Ochsenkühn 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;98:347–54.10.1016/j.fertnstert.2012.04.041Search in Google Scholar PubMed

[43] Huang Y, Wang EY, Du QY, Xiong Y, Guo X, Yu Y, et al. Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages. Reprod Biol Endocrinol. 2015;13:82.10.1186/s12958-015-0075-3Search in Google Scholar PubMed PubMed Central

[44] 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;98:664–70.e2.10.1016/j.fertnstert.2012.05.024Search in Google Scholar PubMed

[45] 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.e1-4.10.1016/j.fertnstert.2012.03.014Search in Google Scholar PubMed

[46] Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016;31:2554–60.10.1093/humrep/dew213Search in Google Scholar PubMed

Received: 2018-02-14
Accepted: 2018-03-19
Published Online: 2018-05-16

©2018 Walter de Gruyter GmbH, Berlin/Boston

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