Assessment of progesterone levels on the day of pregnancy test determination: A novel concept toward individualized luteal phase support

Abstract

Research question: The main objective of the study is to define the optimal trade-off progesterone (P4) values on the day of embryo transfer (ET), to identify low P4-human chorionic gonadotropin (hCG), and to establish whether P4 supplementation started on the hCG day can increase the success rate of the frozen embryo transfer (FET) cycle.

Design: A single-center, cohort, retrospective study with 664 hormone replacement therapy (HRT)-FET cycles analyzed female patients who received vaginal 600 mg/day of P4 starting from 6 days before the FET, had normal P4 values on the day before ET, and whose P4 on the day of the pregnancy test was assessed.

Results: Of the 664 cycles, 69.6% of cycles showed P4 ≥ 10.6 ng/ml, while 30.4% showed P4 < 10.6 ng/ml on the day of the hCG. Of the 411 chemical pregnancies detected, 71.8% had P4-hCG ≥ 10.6 ng/ml (group A), while 28.2% had P4-hCG < 10.6 ng/ml. Of the cycles with P4-hCG < 10.6 ng/ml, 64.7% (group B) were supplemented with a higher dose of vaginal P4 (1,000 mg/day), while 35.3% (group C) were maintained on the same dose of vaginal micronized P4. The live birth rate was 71.9%, 96%, and 7.3% for groups A, B, and C, respectively.

Conclusion: The likelihood to detect P4-hCG < 10.6 ng/ml decreased as the level of serum P4 the day before ET increased. The live birth rate (LBR) was shown to be significantly lower when P4 was low and not supplemented.

Keywords: artificially prepared endometrium; hCG and progesterone assessment; individualization of luteal phase; live birth rate; luteal phase support; progesterone supplementation.

Figure 1

Flow chart of the study population and results. In red are the cycles excluded from the primary outcome. In gold is the supplementation on the day of hCG assessment. Positive hCG was considered when ≥ 10 IU. hCG, human chorionic gonadotropin.

Figure 2

Probability of having progesterone levels < 10.6 on day of pregnancy test according to pre-transfer progesterone levels. ROC curve. Classification of low P on the day of hCG. Considering the P4 value on the day before ET. As a result of this ROC curve, a cutoff point of 13.57 ng/ml was selected with specific sensitivity and specificity values. Therefore, 44.5% of the cycles with progesterone ≤ 1 3.57 ng/ml, despite being “high”, have a low progesterone value on the day of hCG. ROC, receiver operating characteristic; hCG, human chorionic gonadotropin; P4, progesterone; ET, embryo transfer.

Figure 3

Percentage of miscarriage and live birth per positive hCG (≥10 IU). Note that groups A and C do not reach 100% because group A has three VIG (>12 weeks) and 1 still birth (malformation) and group C has two VIG (>12 weeks). VIG, voluntary interruption of gestation; hCG, human chorionic gonadotropin. Miscarriage p < 0.0001; live birth p < 0.0001.

Figure 4

Miscarriage/pregnancy in the different groups of patients (per progesterone).