Risk of premature luteinization in IVF cycles and its impact on clinical pregnancy rate

Manisha Choudhary; Sangita Sharma; Mohan Lal Swarankar; Shiv Lal Bhardwaj

doi:10.18203/2320-6012.ijrms20160020

Authors

Manisha Choudhary Department of Obstetrics & Gynaecology, Mahatma Gandhi Medical College & Hospital, Jaipur
Sangita Sharma Department of Obstetrics & Gynaecology, Mahatma Gandhi Medical College & Hospital, Jaipur
Mohan Lal Swarankar Department of Obstetrics & Gynaecology, Mahatma Gandhi Medical College & Hospital, Jaipur
Shiv Lal Bhardwaj Department of Obstetrics & Gynaecology, Mahatma Gandhi Medical College & Hospital, Jaipur

DOI:

https://doi.org/10.18203/2320-6012.ijrms20160020

Keywords:

GnRH agonist, GnRH antagonist, Progesterone, Premature luteinization

Abstract

Background: Premature luteinization (PL) refers to a rise in serum progesterone (P4) levels on the day of HCG administration (1-4). Most studies use an absolute P4 level on the day of HCG administration as an indicator of PL. This study is carried out with the aim to evaluate the incidence of premature luteinizaition (P4 >1.5ng/ml on the day of HCG) and factors influencing it in both agonist and antagonist cycles & its effect on clinical outcome.

Methods: 400 Patients treated by IVF/ICSI at Jaipur fertility centre (ART Unit of Mahatma Gandhi University of Medical Sciences and Technology) from January 2014 to June 2015 were included in this retrospective clinical study. 200 patients were taken in agonist group and 200 in antagonist group. Ovulation induction was given with r-FSH/HMG in both protocols. P4 along with E2, LH and number of oocytes on the day of HCG were taken for study.

Results: Premature luteinization or PL (P4 > 1.5 ng/ml) was noticed in 16% cases in the agonist group and 6% in the antagonist group (p-0.002). In our study the factors predisposing to PL were agonist protocol (16% Vs. 6%, p-0.002), total dose of gonadotrophins > 2000 IU ( 17.69 % Vs. 2.29, p-0.000), >10 follicles of > 14mm on the day of HCG with E2 Levels > 2500 pg/ml (33.33 % Vs. 0%, p-0.000) in agonist protocol and (17.39% Vs. 2.59%, p-0.000) in antagonist protocol.

The clinical pregnancy rate was significantly reduced in cases with PL (32.73% Vs 12.5%, p-0.037) in agonist group. Though the difference was not statistically significant in antagonist group (32.97% Vs 8.33 %, P-0.144),this could be due to large difference in the proportion of sample size.

Conclusions: Despite the use of GnRH analogues, risk of premature rise of progesterone is still there. The risk mainly depends on ovarian response. The high responders with high no of > 14mm follicles, high E2 Levels > 2500 pg/ml and high doses of gonadotrophins used are associated with high risk of PL. As premature rise in P4 level has significant Impact on clinical pregnancy rate (CPR), identification of high risk factors & their proper management can reduce the incidence of PL & cycle cancellation rate as well as can improve the clinical outcome.

Metrics

Metrics Loading ...

References

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

Ubaldi F, Albano G, 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 ICSI cycles. Hum Repord. 1996;11:1405-7.

Bosch E, Valencia I, Escudero E, Crespo J, Simón C, Remohí J, et al. Premature luteinization during gonadotrophin releasing hormone antagonist cycles and its relationship with in-vitro fertilization outcome. Fertil Steril. 2003;80:1444-9.

Hofmann GE, Khoury J, Johnson CA, Thie J, Scott Jr RT. Premature luteinization during controlled ovarian hyprestimulation for in-vitro fertilization embryo transfer has no impact on pregnancy outcome. Fertil Steril. 1996;66 :980-6.

Hofmann GE, Bentzien F, Bergh PA, Garrisi GJ, Williams MC, Guzman I, et al. Premature luteinization in COH has no adverse effect on oocyte and embryo quality. Fertil Steril. 1993;60:675-9.

Silverberg KM, Martin M, Olive DL, Burns WN, Schenken RS. Elevated serum progesterone levels on the day of HCG administration in in-vitro fertilization cycles do not adversely affect embryo quality. Fertil Steril. 1994;6:508-13.

Edelstein MC, Seltman HJ, Cox BJ, Robinson SM, Shaw RA, Muasher SJ. Progesterone level on the day of HCG administration in cycles with GnRH. agonist suppression are not predictive of pregnancy outcome. Fertil Steril. 1990;54:853-7.

Check JH, Chase JS, Nowroozi K, Dietterich CJ. Premature luteinization: treatment and incidence in natural cycles. Hum Reprod. 1991;6:190-3.

Givens CR, Schriock ED, Dandekar PV, Martin MC. Elevated serum progesterone levels on the day of HCG administration do not predict outcome in assisted reproduction cycles. Fertil Steril. 1994;62:1011-7.

Hoff JD, Quigley ME, Yen SS. Hormonal dynamics at midcycle : a revaluation. J Clin Endocrinol Metab. 1983;57:792-6.

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.

Melo MA, Meseguer M, Garrido N, Bosch E, Pellicer A, Remohi J. The significance of premature luteinization in an oocyte donation program. Hum Reprod. 2006;21:1503-7.

Polotsky AJ, Daif JL, Jindal S, Lieman HJ, Santoro N, Pal L. Serum progesterone on the day of HCG administration predicts clinical pregnancy of sibling frozen embryos. Fertil Steril. 2009;92:1880-5.

Fanchin R, Righini C, Olivennes F, de Ziegler D, Selva J, Frydman R. Premature progesterone elevation does not alter oocyte quality in in-vitro fertilization. Fertil steril. 1996;65:1178-83.

Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamiltion F, Meldrum DR. Lower Pregnancy rate with Premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991;55:563-6.

Silverberg KM, Burns WN, Olive DL, Riehl RN, Schenken RS. Serum progesterone levels predict success of in-vitro fertilization embryo transfer in patients stimulated with leuprolide acetated and HMG. Clin Endocrinol Metab. 1991;73:797-803.

Elnashar AM. Progesterone rise on the day of HCG administration (Premature luteinization) in IVF. An overdue update. Assist Reprod Genet. 2010;27:149-55.

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. 2010;27(6):1822-28.

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. EJ of obst & gyne and Repord biology. 2012;162(2):165-8.

Saadat P, Boostanfar R, Slater CC, Tourgeman DE, Stanczyk FZ, Paulson RJ. Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyper stimulation: impact of GnRH agonists versus antagonists. Fertil Steril. 2004;82:167-71.

Kyrou D, Popovic – Todorovic B, Fatemi H M et al. Does the estradiol level on the day HCG administration have an impact on pregnancy rates in patients treated with r-FSH/GnRH antagonist ? Hum Reprod. 2009;24:2902-9.

Papanikolaou EG, Kolibianakis EM, Pozzobon C, Tank P, Tournaye H, Bourgain C, et al. Progesterone rise on the day of HCG 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.

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.

Van VI, Fatemi HM, Blockeel C, Van Lommel L, Schuit F, Kolibianakis EM, et al. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed online. 2011;22:263-71.

Bosch E, Labarta E, Crespo J, Simón 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: 2092-100.

Papanikalaou 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 secretary changes. Hum Reprod 2005;20:1541-7.

Venetis CA, 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;19:433-57.

Filicori M, Cognigni GE, Pocoganoli P, Tabarelli C, Spettolli D, Taraborrelli S, et al. Modulation of folliculo genesis and steroidogenesis in women by graded Menotropin administration. Hum Reprod. 2002;17:2009-15.

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