The Role of hCG Triggering Progesterone Levels: A Real-World Retrospective Cohort Study of More Than 8000 IVF/ICSI Cycles

Raffaella De Cesare,Paolo Emanuele Levi-Setti,Paola Persico,Valentina Canevisio,Emanuela Morenghi,Annamaria Baggiani,Federico Cirillo,Maria Teresa Sandri,Camilla Ronchetti

doi:10.3389/fendo.2020.547684

Raffaella De Cesare, Paolo Emanuele Levi-Setti + Show 7 more

Open Access

https://doi.org/10.3389/fendo.2020.547684

Copy DOI

Abstract

Objective: To assess the association between serum ovulation trigger progesterone (P) levels and the outcome of in vitro fertilization cycles.Design Setting: Real world single-center retrospective cohort study.Patient Intervention(s): All fresh cleavage and blastocyst-stage embryo transfers (ETs) performed from January 2012 to December 2016.Main outcome Measure(s): The impact of premature high serum P levels cycles in terms of clinical pregnancy rates (CPRs) and live birth rates (LBRs).Results: 8,034 ETs were performed: 7,597 cleavage-stage transfers and 437 blastocyst transfers. Serum P levels demonstrated to be inversely related to CPR (OR 0.72, p < 0.001) and LBR (OR 0.73, p < 0.001). The progressive decrease of LBR and CPR started when P levels were >1 ng/ml in a good prognosis cleavage ET subgroup, whereas in patients with worse prognosis only for P ≥ 1.75 ng/ml. In the blastocyst ET subgroup, the negative effect of P elevation was reported only if P was >1.75 ng/ml. CPR (OR 0.71 (0.62–0.80), p < 0.001) and LBR (OR 0.73 (0.63–0.84), p < 0.001) in thawed cycles resulted statistically significantly higher than in fresh cycles in the cleavage-stage subgroup. In the blastocyst group, no significant difference resulted between thawed and fresh cycles, independently of P levels [CPR OR 0. 37 (0.49–1.09), p = 0.123; LBR OR 0.71 (0.46–1.10), p = 0.126].Conclusion: High P levels decrease CPR as well as LBR in both cleavage and blastocyst ET. In the cleavage group, for P levels below 1.75 ng/ml, our data suggest the possibility to wait until day 5 for ET, and if P level is ≥1.75 ng/ml, it should be considered to freeze all embryos and postpone the ET.Clinical Trial Registration: ClinicalTrials.gov, ID: NCT04253470

Highlights

The association between serum progesterone (P) levels, measured on the day of ovulation trigger, and the outcome of in vitro fertilization (IVF) cycles, has been one of the major controversies in the field of ovarian stimulation endocrinology [1, 2]
Some authors report that a premature increase of P during ovarian stimulation could be caused by a loss of activity of luteinizing hormone (LH) and human chorionic gonadotropins [12, 13]
The use of recombinant LH or follicular stimulating hormone (FSH), HMG, the type of protocol, the choice of rescue cycles with agonist triggering, or the pre-treatment taking of oral contraceptive pills as other variables were considered in a preliminary univariate assay, but results were not confirmed in the consequent multivariate analysis in which no difference was depicted among the different groups

Summary

Introduction

The association between serum progesterone (P) levels, measured on the day of ovulation trigger, and the outcome of in vitro fertilization (IVF) cycles, has been one of the major controversies in the field of ovarian stimulation endocrinology [1, 2]. Since 1991, many studies have emphasized that a premature and excessive P increase just before the induction of ovulation might negatively affect the outcome of the IVF cycle [3,4,5,6]. The high doses of exogenous follicular stimulating hormone (FSH) used in ovarian stimulation cycles could cause the rise of P levels toward the end of the follicular phase. Some authors report that a premature increase of P during ovarian stimulation could be caused by a loss of activity of LH and human chorionic gonadotropins (hCGs) [12, 13]

Methods

Results

Discussion

Conclusion