High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

Antonio Requena, María Cruz, Ernesto Bosch, Marcos Meseguer, Juan Antonio García-Velasco, Antonio Requena, María Cruz, Ernesto Bosch, Marcos Meseguer, Juan Antonio García-Velasco

Abstract

Background: The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response.

Methods: We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: <0.5 ng/ml (<p10), 0.50-0.70 ng/ml (p10-p25), 0.71-1.00 ng/ml (p25-p50), 1.01-1.40 ng/ml (p50-p75), 1.41-1.80 ng/ml (p75-p90) and >1.81 ng/ml (>p90). Ovarian response was classified as high when>=20 oocytes were retrieved or when estradiol was >=3000 pg/ml. Clinical outcomes of each subgroup were analyzed. We also examined data from frozen-thawed embryo transfers. Results were analyzed with Student's t- test to compare continuous variables and chi-squared test to compare proportions. A p-value of< =0.05 was considered statistically significant.

Results: The progesterone concentration increased with ovarian response, and elevated progesterone did not show a significant clinical impact on implantation rate and pregnancy rates. These data provide evidence that progesterone levels higher than 1.8 ng/ml do not have detrimental effect on oocyte quality or endometrial receptivity.

Conclusions: These data allow us to conclude that high progesterone levels correlate significantly with high estradiol levels and that in high responder women; progesterone levels do not show a significant clinical impact on results.

Figures

Figure 1
Figure 1
High estradiol concentrations are associated with high estradiol concentrations.
Figure 2
Figure 2
Implantation rates according progesterone levels. (*, p = 0.045).
Figure 3
Figure 3
Pregnancy rates according progesterone levels. (*, p = 0.044).

References

    1. Bosch E, Valencia I, Escudero E, Crespo J, Simon C, Remohi J, Pellicer A. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril. 2003;80:1444–1449.
    1. Azem F, Tal G, Lessing JB, Malcov M, Ben-Yosef D, Almog B, Amit A. 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;24:368–372.
    1. Bosch E, Labarta E, Crespo J, Simon C, Remohi J, Jenkins J, Pellicer A. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010;25:2092–2100.
    1. 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;13:343–355.
    1. 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;23:187–195.
    1. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003;9:515–522.
    1. Fanchin R, Righini C, Olivennes F, Ferreira AL, de Ziegler D, Frydman R. Consequences of premature progesterone elevation on the outcome of in vitro fertilization: insights into a controversy. Fertil Steril. 1997;68:799–805.
    1. Hofmann GE, Bentzien F, Bergh PA, Garrisi GJ, Williams MC, Guzman I, Navot D. Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality. Fertil Steril. 1993;60:675–679.
    1. Ubaldi F, Albano C, Peukert M, Riethmuller-Winzen H, Camus M, Smitz J, Van Steirteghem A, Devroey P. Subtle progesterone rise after the administration of the gonadotrophin-releasing hormone antagonist cetrorelix in intracytoplasmic sperm injection cycles. Hum Reprod. 1996;11:1405–1407.
    1. Smitz J, Andersen AN, Devroey P, Arce JC. MERIT Group. Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Hum Reprod. 2007;22:676–687.
    1. Kyrou D, Popovic-Todorovic B, Fatemi HM, Bourgain C, Haentjens P, Van Landuyt L, Devroey P. Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod. 2009;24:2902–2909.
    1. Kyrou D, Al-Azemi M, Papanikolaou EG, Donoso P, Tziomalos K, Devroey P, Fatemi HM. 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;162:165–168.
    1. 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.
    1. Alikani M, Calderon G, Tomkin G, Garrisi J, Kokot M, Cohen J. Cleavage anomalies in early human embryos and survival after prolonged culture in-vitro. Hum Reprod. 2000;15:2634–2643.
    1. 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;10:2432–2437.
    1. Sharara FI, McClamrock HD. Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome. Hum Reprod. 1999;14:2777–2782.
    1. Kosmas IP, Kolibianakis EM, Devroey P. Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review. Hum Reprod. 2004;19:2446–2453.
    1. Kilicdag EB, Haydardedeoglu B, Cok T, Hacivelioglu SO, Bagis T. Premature progesterone elevation impairs implantation and live birth rates in GnRH-agonist IVF/ICSI cycles. Arch Gynecol Obstet. 2010;281:747–752.
    1. Ubaldi F, Camus M, Smitz J, Bennink HC, Van Steirteghem A, Devroey P. Premature luteinization in in vitro fertilization cycles using gonadotropin-releasing hormone agonist (GnRH-a) and recombinant follicle-stimulating hormone (FSH) and GnRH-a and urinary FSH. Fertil Steril. 1996;66:275–280.
    1. Urman B, Alatas C, Aksoy S, Mercan R, Isiklar A, Balaban B. Elevated serum progesterone level on the day of human chorionic gonadotropin administration does not adversely affect implantation rates after intracytoplasmic sperm injection and embryo transfer. Fertil Steril. 1999;72:975–979.
    1. Fatemi HM, Doody K, Griesinger G, Witjes H, Mannaerts B. High ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in a GnRH-antagonist protocol. Hum Reprod. 2013;28:442–452.
    1. Wu Z, Li R, Ma Y, Deng B, Zhang X, Meng Y, Chen X, Liu P, Qiao J. Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod Biomed Online. 2012;24:511–520.
    1. Munoz M, Cruz M, Humaidan P, Garrido N, Perez-Cano I, Meseguer M. Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics. Reprod Biomed Online. 2012;25:382–389.
    1. Chetkowski RJ, Kiltz RJ, Salyer WR. In premature luteinization, progesterone induces secretory transformation of the endometrium without impairment of embryo viability. Fertil Steril. 1997;68:292–297.
    1. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril. 2010;93:636–641.
    1. Labarta E, Martinez-Conejero JA, Alama P, Horcajadas JA, Pellicer A, Simon C, Boch E. 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;26:1813–1825.
    1. Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010;94:2054–2058.
    1. Melo MA, Meseguer M, Garrido N, Bosch E, Pellicer A, Remohi J. The significance of premature luteinization in an oocyte-donation programme. Hum Reprod. 2006;21:1503–1507.
    1. Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, Zhu G. 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.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever