Elevated progesterone level and its consequences on IVF


  • Sankar Kumar Das 1Department of Obstetrics and Gynecology, Swagta Hospital and Research Center, Bongaigaon Assam, India 2Department of Obstetrics and Gynecology, Gauhati Medical College and Hospital, Guwahati, Assam, India
  • Priyanka Roy 1Department of Obstetrics and Gynecology, Swagta Hospital and Research Center, Bongaigaon Assam, India 3Department of Obstetrics, Assam Medical College and Hospital, Dibrugarh, Assam, India
  • Krishna Kalita 1Department of Obstetrics and Gynecology, Swagta Hospital and Research Center, Bongaigaon Assam, India 4Department of Obstetrics and Gynecology, Assam Agricultural University, Jorhat, Assam, India




Embryo, Endometrium, IVF, Progesterone


Background: Understanding of the embryo-endometrium dialogue is still far from being understood. During conventional in vitro fertilization cycles, progesterone elevation on the day of human chorionic gonadotropin administration refers to rising progesterone levels in the absence of either premature or a luteinizing hormone surge. Most research have reported that elevated progesterone had an adverse impact on the endometrial environment of fresh cycles, leading to a decrease in pregnancy rates.

Methods: The current study was undertaken at Swagat hospital and research Centre, Bongaigaon, Assam (India). Fifty patients undergoing in vitro fertilization (IVF) were selected for the study. Baseline estimation of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), (estrogen) E2 and (transvaginal sonography) TVS was done. The patients were grouped on the basis of their progesterone levels on the day of hCG trigger, with the cutoff for defining premature progesterone rise being (progesterone) P4≥ 3ng/ml. Final oocyte maturation was induced with hCG. Oocyte retrieval was performed 34-36 h after hCG. Two to three embryos of day 3 cleavage stage were transferred under TVS guidance. The parameters obtained from each cycle were recorded. Statistical analysis was performed. Probability (P) value <0.05 was considered statistically significant. A sonographic confirmation of pregnancy was performed 2 weeks after β-hCG positive.

Results: On dividing the patients into two groups, based on the cut off of P4 as 3ng/ml, it was observed that the no of cases that conceived was significantly higher in the subjects whose P4 level was less than or equal to 3ng/ml than the subjects whose P4 level was more than 3ng/ml.

Conclusions: Elevated P4 i.e. Progesterone level just before trigger is a reflection of endometrial maturity that can cause disparity between endometrial and embryonic ageing and therefore hamper implantation or cause failure in assisted reproductive technology (ART).


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(6):1477-84 e1-5.

Al-Azemi M, Kyrou D, Kolibianakis EM, Humaidan P, Van Vaerenbergh I, Devroey P, et al. Elevated progesterone during ovarian stimulation for IVF. Reprod Biomed Online. 2012;24(4):381-8.

Huang B, Li Z, Zhu L, Hu D, Liu Q, Zhu G, Zhang H. Progesterone elevation on the day of HCG administration may affect rescue ICSI. Reprod Biomed Online. 2014;29(1):88-93.

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.

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.

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. Human Reprod Update. 2007;13(4):343-55.

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(3):464-70.

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. Human Reprod. 2010;25(8):2092-100.

Ochsenkun R, Arzberger A, von Schonfeldt 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.

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

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(2):187-95.

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 editorial comment. Obstet Gynecol Surv. 2011;66(12):763-4.

Kasum M, Radakovic B, Simunic V, Oreškovic S. Preovulatory progesterone rise during ovarian stimulation for IVF. Gynecol Endocrinol. 2013;29(8):744-8.

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.

Saadat P, Boostanfar R, Slater CC, Tourgeman DE, Stanczyk FZ, Paulson RJ. Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: Impact of gonadotropin-releasing hormone agonists versus antagonists. Fertil Steril. 2004;82:167-1.

Van Vaerenbergh I, Fatemi HM, Blockeel C, Van Lommel L, 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.

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.

Bo Huang, Xinling Ren, Li Wu, Lixia Zhu, Bei Xu, Yufeng Li, Jihui Ai, et al. Elevated Progesterone Levels on the Day of Oocyte Maturation May Affect Top Quality Embryo IVF Cycles. PLoS One. 2016;11(1):e0145895.

Fanchin R, de Zeigler, Taieb J, Hazout A, Frydman R. Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer. Fertil Steril.1993;59:1090-4.

Li M, Xie Y, Park H, Kumar A, Hubert G, Buyalos R. The effects of elevated serum progesterone level at the day of hCG injection on clinical outcome in IVF-ET patients. Fertil Steril. 2013;100(3):S7.

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.

Mascarenhas M, Kamath MS, Chandy A, Kunjummen AT. Progesterone/estradiol ratio as a predictor in the ART cycles with premature progesterone elevation on the day of hCG trigger. J Reprod Infertil. 2015;16:155.

Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor blind controlled trial. Hum Reprod.2006;21:3217-27.






Original Research Articles