Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles

Capsule:
This retrospective analysis showed that premature progesterone rise (PPR) impaired in vitro fertilization outcomes in fresh embryo transfer, whereas no negative impact on frozen embryo transfer was observed, implying deleterious effects of PPR on endometrial receptivity.

Authors:
Rui Huang, M.D., Cong Fang, M.D., Shuyi Xu, Ph.D., Yanhong Yi, M.D., Xiaoyan Liang, M.D.

Volume 98, Issue 3, Pages 664-670.e2, September 2012

Abstract:

Objective:
To investigate the occurrence of premature progesterone rise (PPR) in GnRH agonist long or short protocol, address the relationship between circulating progesterone levels and live birth rates, and explore the possible mechanism through which PPR affects clinical outcomes and the possible factors related to the occurrence of PPR.

Design:
Retrospective analysis.

Setting:
Reproductive medicine center of a public hospital.

Patient(s):
2,566 patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment with GnRH agonist long or short protocol.

Intervention(s):
None.

Main Outcome Measure:
Live birth rates.

Result(s):
The corresponding incidence of PPR in long or short protocol was 22.86% (393/1719) or 27.63% (234/847) with the cutoff value 1.2 ng/ml or 2.0 ng/ml being used to define PPR, respectively. Live birth rates decreased under the condition of PPR (40.65% vs. 29.77% in long protocol, P=0.004; 30.18% vs. 23.50% in short protocol, P=0.083). Logistic regression analysis showed that serum progesterone level on the day of hCG administration was a strong predictor of live birth rate both in long and in short protocol. Live birth rates in frozen embryo transfer cycles had no significant difference between groups with or without PPR (29.31% vs. 25.35% in long protocol, P=0.213; 24.84% vs. 24.22% in short protocol, P=0.881). Multivariate regression analysis showed that exogenous gonadotropin dose, the duration of stimulation, estradiol (E2) and luteinizing hormone (LH) level on the day of hCG administration, the number of oocytes retrieved and basal FSH level were all involved in PPR.

Conclusion(s):
In GnRH agonist cycles, PPR negatively correlated with live birth rate in fresh embryo transfer cycles while no adverse impact on frozen embryo transfer was observed, implying that PPR may have deleterious effects on endometrial receptivity.

  • I agree with these findings and we definitely have taken progesterone into consideration for the past 3 decades

  • Micah Hill

    Thank you Dr. Huang and colleges for a very nice study which
    is very consistent with recent published data showing a non-linear decrease in
    pregnancy rates with rising progesterone levels on the day of hCG. This study furthered that knowledge by demonstrating
    similar declines in the short protocol.

    Question 1: The
    majority of such studies have been in cleavage stage transfers. You methods states “no more than 3 embryos transferred
    on day 3”, so is it correct to state all the patients received day 3 transfers
    in this study?

    Question 2: Previous studies and this current study show a
    strong positive correlation between total exogenous FSH dose and elevated
    progesterone levels. Further, the Bosch
    paper showed lower rates of elevated progesterone in patients receiving exogenous
    LH+FSH versus those receiving FSH alone.
    They hypothesized that LH activation of CYP 17 allows the progesterone
    to be converted to androgens, thus decreasing the rates of elevated
    progesterone. Do you have serum FSH
    values between the two protocols on the day of hCG and were those also higher
    in the short protocol patients? Do you
    hypothesize that the elevated progesterone in the short protocol patients was a
    result of premature luteinization?

    Thanks in advanced for your thoughts.

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