Abstract

BackgroundThe effect of progesterone elevation (PE) on the day of human chorionic gonadotropin (hCG) administration on the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles is a matter of ongoing debate. The replacement of cleavage-stage embryos with blastocyst-stage embryos for transfer was proposed to avoid the possible impairment of PE in fresh cycles. This study aimed to assess the association between PE on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates (CPRs) in IVF/ICSI cycles with embryos transferred at different developmental stages (cleavage and blastocyst). Moreover, a secondary aim was to determine the thresholds at which PE has a detrimental effect on CPRs.MethodsThis single-center retrospective cohort study included more than 10,000 patients undergoing day 3 cleavage-stage embryo transfer (ET) and 1146 patients undergoing day 5 blastocyst-stage embryo transfer (ET) using gonadotropin and GnRH agonist for controlled ovarian stimulation.ResultsSerum PE was inversely associated with CPRs in both cleavage- and blastocyst-stage ET cycles. In the day 3 ET cycles, CPRs (progesterone levels < 0.5 ng/ml, 49.2 %) significantly declined when the progesterone concentration reached 1.0 ng/ml (45.5 %) and decreased further when the progesterone concentration increased to 1.5 ng/ml (36.2 %). In the day 5 blastocyst-stage ET cycles, patients with serum progesterone levels ≥1.75 ng/ml had significantly lower CPRs (31.3 % VS. 41.4 %, p < 0.001) compared to patients with serum progesterone levels <1.75 ng/ml. The negative association of PE with CPRs was noted in both ET groups, even after adjusting for confounders. Furthermore, the developmental stage of the transferred embryos was not linked to the effect of PE on CPRs because the interaction between the developmental stage of the transferred embryos and PE was not significant.ConclusionsPE on the day of hCG administration is associated with decreased CPRs in GnRH agonist IVF/intracytoplasmic sperm injection (ICSI) cycles regardless of the developmental stage of the transferred embryos (cleavage versus blastocyst stage).

Highlights

  • The effect of progesterone elevation (PE) on the day of human chorionic gonadotropin administration on the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles is a matter of ongoing debate

  • Several relatively clear causes of infertility were present in the patients in the day 3 and day 5 embryo transfer (ET) groups, including tubal pathology (44.5 and 58.5 %, respectively), male factors (27.5 and 29.8 %, respectively), advanced age (≥35 years, 11.1 and 14.6 %, respectively), polycystic ovary syndrome (PCOS) (6.2 and 11.5 %, respectively), and endometriosis (3.5 and 3.3 %, respectively)

  • This study showed that PE on the day of human chorionic gonadotropin (hCG) administration decreased Clinical pregnancy rate (CPR) in both cleavage- and blastocyststage ET cycles using gonadotropin and gonadotropin-releasing hormone (GnRH) agonist for controlled ovarian stimulation

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Summary

Introduction

The effect of progesterone elevation (PE) on the day of human chorionic gonadotropin (hCG) administration on the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles is a matter of ongoing debate. This study aimed to assess the association between PE on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates (CPRs) in IVF/ICSI cycles with embryos transferred at different developmental stages (cleavage and blastocyst). A secondary aim was to determine the thresholds at which PE has a detrimental effect on CPRs. Despite the widespread use of gonadotropin-releasing hormone (GnRH) analogues for pituitary down-regulation, progesterone elevation (PE), which refers to an increase in serum progesterone concentrations, still occurs at different frequencies on the day of human chorionic gonadotropin (hCG) administration for final oocyte maturation in fresh in vitro fertilization (IVF) cycles [1]. The hypothesis regarding endometrial receptivity is seemingly more convincing because of the results of gene expression studies on the endometrium [16, 17] and studies showing that the live birth rates of women implanted with frozen-thawed embryos or donor oocytes from fresh cycles did not significantly differ between those with PE and those without PE [1, 18]

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