Abstract

BackgroundEndometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day.MethodsThis prospective cohort study includes patients who underwent single euploid FET. All patients received HRT with oestradiol valerate (EV) and 100 mg of intramuscular (IM) progesterone (P). FET was scheduled 117–120 h after the first IM administration of 100 mg P. The serum P level was analyzed 1 h before the embryo transfer (ET). In all cycles, only embryos that were biopsied on day 5 were utilized for FET. Next generation sequencing (NGS) was used for comprehensive chromosomal analysis.ResultsOverall, the ongoing pregnancy rate (OPR) was 58.9% (99/168). Data were then categorized according to the presence (Group I; n = 99) or the absence (Group II; n = 69) of an ongoing pregnancy. No significant differences regarding, female age, body mass index (BMI), number of previous miscarriages, number of previous live birth, sperm concentration, number of oocytes retrieved, number of mature oocytes (MII), rate of fertilized oocytes with two pronuclei (2PN), trophectoderm score, inner cell mass (ICM) score, endometrial thickness (mm), oestrodiol (E2) and P levels prior to IM P administration were found between two groups. The P levels on the day of ET (ng/ml) were significantly higher in Group I (28 (5.6–76.4) vs 16.4 (7.4–60) p = 0.039). The P level on the day of ET was a predictor of a higher OPR (p < 0.001 OR: 1.033 95%CI [1.009–1.056]) after multivariate analysis. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.716 (0.637–0.795). The optimal cut-off value for prediction of the OPR was a P level of 20.6 ng/ml (71.7% sensitivity, 56.5% specificity).ConclusionsThe present study suggests a minimum threshold of the serum P value on the day of ET that needs to be reached in HRT cycles to optimize the clinical outcome. Individualization of the P dosage should be evaluated in further studies.

Highlights

  • The number of frozen-warmed embryo transfer (FET) procedure has been increasing worldwide in the last decade

  • The best endometrial preparation protocol is still the subject of an ongoing debate [1,2,3]; hormone replacement therapy (HRT) is a more popular regimen owing to the opportunity to schedule the day of embryo transfer and its reduced monitoring requirements [4]

  • The increasing number of frozen-warmed embryo transfers (FET) procedures raises the question of the serum P level that is required to optimize the pregnancy outcome because defining an optimal level may allow the individualization of FET in HRT

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Summary

Introduction

The number of frozen-warmed embryo transfer (FET) procedure has been increasing worldwide in the last decade. The best endometrial preparation protocol is still the subject of an ongoing debate [1,2,3]; hormone replacement therapy (HRT) is a more popular regimen owing to the opportunity to schedule the day of embryo transfer and its reduced monitoring requirements [4]. Endometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day

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