Impact of late-follicular phase elevated serum progesterone on cumulative live birth rates: is there a deleterious effect on embryo quality?

Hum Reprod. 2018 May 1;33(5):860-868. doi: 10.1093/humrep/dey031.

Abstract

Study question: Is elevated late-follicular phase progesterone (EP) associated with a deleterious impact on embryo quality (EQ) and cumulative live birth rates (LBRs)?

Summary answer: EP was associated with a decrease in embryo utilization and cumulative LBRs.

What is known already: Ovarian stimulation promotes the production of progesterone (P) which adversely affects IVF pregnancy outcomes. However, evidence regarding a potential association between EP an EQ is lacking.

Study design, size, duration: A retrospective analysis of all GnRH antagonist down-regulated ICSI cycles followed by a fresh embryo transfer (ET) between 2010 and 2015 was performed. The sample was stratified according to the following P levels on the day of ovulation triggering: ≤0.50, 0.51-1.49 and ≥1.50 ng/ml. The primary outcomes were embryo utilization rates (number of embryos transferred or cryopreserved) and cumulative LBR, defined as the occurrence of the first live-birth after either the fresh or one of the subsequent frozen ET.

Participants/materials, setting, methods: Overall, 3400 cycles were included in the analysis, using multivariable regression to account for potential confounding.

Main results and the role of chance: Female age and the number of oocytes retrieved increased significantly with increasing serum P values. Utilization rates decreased linearly as P increased for Day 3 embryos (72.3, 63.0 and 45.4%, respectively), while for Day 5 embryos only the EP group was associated with a significant decrease (48.8, 47.8 and 38.8%, respectively). EP was also associated with decreased fresh and cumulative LBRs.

Limitations reasons for caution: The main limitations of this study were its retrospective nature and the fact that it was restricted to GnRH antagonist cycles.

Wider implications of the findings: These results raise the question whether EP may also be associated with a decrease in cumulative pregnancy outcomes by increasing embryo wastage. Further studies may evaluate the potential benefit of additional measures besides the freeze-all strategy to avoid this issue, such as lowering the stimulation dose or applying a step-down protocol.

Study funding/competing interest(s): None.

MeSH terms

  • Adult
  • Age Factors
  • Birth Rate
  • Embryo Transfer / methods*
  • Embryonic Development / physiology*
  • Female
  • Follicular Phase / blood*
  • Humans
  • Live Birth
  • Oocyte Retrieval
  • Ovulation Induction
  • Pregnancy
  • Pregnancy Outcome
  • Progesterone / blood*
  • Retrospective Studies
  • Sperm Injections, Intracytoplasmic

Substances

  • Progesterone