P-648 How often does elevated progesterone occur? A systematic review
Authors: Lim Y  C , Hamdan M , Cheong Y 
Published: July 2024

Abstract

Study question
What is the incidence of elevated serum progesterone level during the follicular phase in fresh and frozen ART cycles?

Summary answer
The incidence of elevated progesterone levels varies widely during the follicular phase in both fresh and frozen ART cycles.

What is known already
Progesterone monitoring is often performed for the optimization of ART cycle. Elevated progesterone (EP) noted during ovarian stimulation can lead to cycle cancellation and the implementation of a freeze all strategy as EP is associated with lower pregnancy rates. The introduction of GnRH analogues did not seem to prevent EP. In frozen embryo transfer (FET) cycles, EP can be present even without gonadotropin commencement. Various thresholds have been used to define EP and the incidence of EP reported in the literature varies.

Study design, size, duration
A systematic search of the following electronic databases: EMBASE, MEDLINE, CINAHL and PubMed identified non-randomised comparative cohort studies between the year 2000 to 2022. The following keywords progesterone, assisted reproductive technique and pregnancy outcomes and their respective variants were used. Study selection was performed following initial screen of the titles and abstracts. The full manuscripts were examined for compliance with the inclusion criteria and studies eligible for inclusion in the review were selected.

Participants/materials, setting, methods
PICOS study protocol was used. We included studies reporting per woman data of women undergoing fresh IVF/ICSI cycles (with controlled ovarian stimulation) and FET cycles (natural or medicated), with extractable data on pregnancy outcomes and using serum progesterone monitoring. We excluded interventional studies and studies involving oocyte or gamete donation. Comparisons were made between the population with EP versus non-elevated progesterone in fresh and FET cycles.

Main results and the role of chance
We included 52 studies (N = 53,517 women) for the systematic review. In fresh COS cycles, the incidence of EP at baseline varied from 13.3% to 30% (30% in P &gt; 0.65ng/ml; 13.3% - 23.2% in P &gt; 1.5ng/ml). At ovulation trigger, the incidence of EP ranged from 3.1% to 65%. (33% - 52.2% in P &gt; 0.9ng/ml; 20% - 65% in P &gt; 1.0ng/ml; 13.9% - 31.2% in P &gt; 1.1ng/ml; 17.2% - 54.7% in P &gt; 1.2ng/ml; 21.5% - 32.7% in P &gt; 1.3ng/ml; 4.6% - 44.2% in P &gt; 1.5ng/ml; 7% - 20.1% in P &gt; 1.7ng/ml; 11.9% in P &gt; 1.9ng/ml and 3.1% - 33.6% in P &gt; 2.0ng/ml). The incidence of EP at egg collection ranged from 27.3% to 55.4%. (55.4% in P &gt; 2.0ng/ml; 39.4% in P &gt; 11.7ng/ml and 27.3% in P &gt; 12ng/ml). In frozen cycles, the incidence of elevated progesterone was 68.7% at ovulation trigger in modified natural cycle FET (NC-FET). The incidence of EP before ovulation in NC-FET was 24.4% (P &gt; 1.0ng/ml) and 26.4% (P &gt; 1.57ng/ml).

Limitations, reasons for caution
Observational studies were included in this systematic review with wide variation of progesterone thresholds and timing that increases the clinical heterogeneity. The incidence of EP varies widely among the included studies. The immunoassays used for progesterone measurement were not standardised with questionable accuracy at low levels.

Wider implications of the findings
The incidence of EP varies significantly amongst the studies. We observed similar wide variation of EP incidence at low and high progesterone threshold level. The accuracy of immunoassays on progesterone concentrations &lt;2.5ng/ml has been questioned and the non-standardized timing of progesterone measurement challenges the reliability of the measured progesterone result.

Trial registration number
not applicable