The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study

Robati, Shahin; Wiam, Saab; Durán-Retamal, Montserrat; Saab, Wael; Theodorou, Efstathios; Cawood, Suzanne; Serhal, Paul; Seshadri, Srividya

doi:10.18502/jri.v21i4.4333

The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study

Authors

Shahin Robati ¹

Saab Wiam ²

Montserrat Durán-Retamal ¹

Wael Saab ¹

Efstathios Theodorou ¹

Suzanne Cawood ¹

Paul Serhal ¹

Srividya Seshadri ¹

¹ Institute for Women’s Health, Faculty of Population Health Sciences, University College London, London, United Kingdom

² Department of Obstetrics and Gynaecology, The American University of Beirut Medical Centre, Beirut, Lebanon

10.18502/jri.v21i4.4333

Abstract

Background: The advent of ovarian stimulation within an in vitro fertilization (IVF) cycle has resulted in modifying the physiology of stimulated cycles and has helped optimize pregnancy outcomes. In this regard, the importance of progesterone (P4) elevation at time of human chorionic gonadotrophin (hCG) administration within an IVF cycle has been studied over several decades. Our study aimed to evaluate the association of P4 levels at time of hCG trigger with live birth rate (LBR), clinical pregnancy rate (CPR) and miscarriage rate (MR) in fresh IVF or IVF-ICSI cycles. Methods: This was a retrospective cohort study (n=170) involving patients attending the Centre for Reproductive and Genetic Health (CRGH) in London. The study cohort consisted of women undergoing controlled ovarian stimulation using GnRH antagonist or GnRH agonist protocols. Univariate and multiple logistic regression analyses were used to evaluate the association of clinical outcomes. Differences were considered statistically significant if p<0.05. Results: As serum progesterone increased, a decrease in LBR was observed. Following multivariate logistical analyses, LBR significantly decreased with P4 thresholds of 4.0 ng/ml (OR 0.42, 95% CI:0.17-1.0) and 4.5 ng/ml (OR 0.35, 95% CI:0.12-0.96). Conclusion: P4 levels are important in specific groups and the findings were statistically significant with a P4 threshold value between 4.0-4.5 ng/ml. Therefore, it seems logical to selectively measure serum P4 levels for patients who have ovarian dysfunction or an ovulatory cycles and accordingly prepare the individualized management packages for such patients.

Keywords

art

hCG trigger

In vitro fertilization (IVF)

Live birth rate (LBR)

Ovarian stimulation

Progesterone elevation

Human fertility and embryology authority (HFEA). Fertility treatment 2014-2016 trends and figures. UK: Human fertility and embryology authority. 2018 Mar. 60 p.

Ecochard R, Bouchard T, Leiva R, Abdulla S, Dupuis O, Duterque O, et al. Characterization of hormonal profiles during the luteal phase in regularly menstruating women. Fertil Steril. 2017;108(1):175-82.e1.

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.

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

Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, et al. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Hum Reprod. 2015;30(3):684-91.

Bu Z, Zhao F, Wang K, Guo Y, Su Y, Zhai J, et al. Serum progesterone elevation adversely affects cumulative live birth rate in different ovarian responders during in vitro fertilization and embryo transfer: a large retrospective study. PLoS One. 2014;9(6):e100011.

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. 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.

Santos-Ribeiro S, Polyzos NP, Haentjens P, Smitz J, Camus M, Tournaye H, et al. Live birth rates after IVF are reduced by both low and high progesterone levels on the day of human chorionic gonadotrophin administration. Hum Reprod. 2014;29(8):1698-705.

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(1):106-11.

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 (11):2554-60.

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(8):1859-65.

Harbottle S, Hughes C, Cutting R, Roberts S, Brison D, Association of clinical embryologists & the (ACE) British fertility society (BFS). Elective single embryo transfer: an update to UK best practice guidelines. Hum Fertil (Camb). 2015;18(3):165-83.