The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony.

ABSTRACT:

Study question

Is there an association of progesterone (P₄) on the day of trigger with live birth in autologous ART transfer cycles on day 5 versus day 6?

Summary answer

P₄ had a greater negative effect on live birth in day 6 fresh transfers compared to day 5 fresh transfers.

What is known already

Premature P₄ elevation is associated with lower live birth rates in fresh autologous ART cycles, likely due to worsened endometrial-embryo asynchrony. Few studies have evaluated whether the effect of an elevated P₄ on the day of trigger is different on live birth rates with a day 5 compared to a day 6 embryo transfer.

Study design size, duration

This was a retrospective cohort study with autologous IVF cycles with fresh embryo transfers on day 5 and day 6 from 2011 to 2014. A total of 4120 day 5 and 230 day 6 fresh autologous embryo transfers were included. The primary outcome was live birth, defined as a live born baby at 24 weeks gestation or later.

Participants/materials, setting, methods

Patients from a large private ART practice were included. Analysis was performed with generalized estimating equations (GEE) modeling and receiver operating characteristic (ROC) curves.

Main results and the role of chance

Day 6 transfers were less likely to have good quality embryos (73% versus 83%, P < 0.001) but the cohorts had similar rates of blastocyst stage transfer (92% versus 91%, P = 0.92). Live birth was less likely in fresh day 6 versus day 5 embryo transfers (34% versus 46%, P = 0.01) even when controlling for embryo confounders. In adjusted GEE models, the effect of P₄ as a continuous variable on live birth was more pronounced on day 6 (P < 0.001). Similarly, the effect of P₄ > 1.5 ng/ml on day of trigger was more pronounced on day 6 than day 5 (P < 0.001). Day 6 live birth rates were 8% lower than day 5 when P₄ was in the normal range (P = 0.04), but became 17% lower when P₄ was > 1.5 ng/ml (P < 0.01). ROC curves for P₄ predicting live birth demonstrated a greater AUC in day 6 transfers (AUC 0.59, 95% CI 0.51-0.66) than day 5 (AUC 0.54, 95% CI 0.52-0.55). Interaction testing of P₄ × day of embryo transfer was highly significant (P < 0.001), further suggesting that the effect of P₄ was more pronounced on day 6 embryo transfer. In fresh oocyte retrieval cycles with elevated P₄, a subsequent 760 frozen-thaw transfers did not demonstrate a difference between embryos that were frozen after blastulation on day 5 versus 6.

Limitations reasons for caution

Limitations include the retrospective design and the inability to control for certain confounding variables, such as thaw survival rates between day 5 and day 6 blastocysts. Also, the data set lacks the known ploidy status of the embryos and the progesterone assay is not currently optimized to discriminate between patients with a P₄ of 1.5 versus 1.8 ng/ml.

Wider implications of the findings

This study suggests further endometrial-embryo asynchrony when a slow growing embryo is combined with an advanced endometrium, ultimately leading to decreased live births. This suggests that premature elevated P₄ may be a factor in the lower live birth rates in day 6 fresh embryo transfers. Further studies are needed to evaluate if a frozen embryo transfer cycle can ameliorate the effect of elevated P₄ on the day of trigger among these slower growing embryos that reach blastocyst staging on day 6.

Study funding/competing interests

No external funding was received for this study. There are no conflicts of interest to declare.

Trial registration number

Not applicable.

SUBMITTER: Healy MW 

PROVIDER: S-EPMC6260420 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature