P-692 Intra-subject variability of mid-luteal progesterone levels in natural/modified natural frozen embryo transfer cycles (NC/MNC): can we predict the need for luteal phase support?
Authors: Agius M  P , Vanhie A , Lie Fong S 
Published: July 2024

Study question

Are progesterone levels different in a NC versus a MNC? What is the predictive value of progesterone for the level in a next cycle?

Summary answer

Progesterone levels were not different in the mid-luteal phase of natural or modified natural cycles and only moderately agree with progesterone in a subsequent cycle.

What is known already

Progesterone is essential for successful implantation and pregnancy. Classical studies have shown considerable variability in progesterone levels during the luteal phase. More recently, progesterone levels during the mid-luteal phase have regained interest, in order to improve chances of pregnancy in frozen embryo transfer cycles. Several studies have suggested that if progesterone on the day of embryo transfer are below a certain cut off level, progesterone production would not be sufficient and luteal support should be provided.

Study design, size, duration

This was a prospective observational study at a tertiary fertility centre in Belgium, performed between January 2022 until March 2023. Serum progesterone on the day of frozen embryo transfer was measured in all patients undergoing frozen embryo transfer in a natural (NC) or modified natural cycle (MNC). Patients were eligible for the current study if at least two progesterone levels in two frozen embryo transfer cycles were available.

Participants/materials, setting, methods

A linear mixed model was used to calculate systematic differences in progesterone levels between NC and MNC. The intra-subject agreement was quantified by means of the intra-class correlation coefficient (ICC) with 95% confidence interval. The ICC ranges between 0 and 1, with high values (&gt; 0.75) indicating a good to excellent level of agreement between measurements taken in the same subject. Progesterone levels were measured with COBAS Elecsys ECLIA progesteron assay by Roche Diagnostics.

Main results and the role of chance

All women were between 18 and 40 years of age. Forty patients with at least two frozen embryo transfers in NC and in MNC were included, i.e. 87 cycles. Their mean age was 32 (26-42) years, the mean BMI was 23.1 (16.9-34.5) kg/m2. Mean progesterone levels on the day of transfer were 13.0 ng/ml (11.0-15.0) in NC and 13.8 ng/ml (12.0-15.6) in MNC. These levels were not systematically different (P = 0.47). The intra-subject agreement showed an ICC of 0.66 in NC and 0.61 in MNC. Hence, our data indicate that progesterone levels in the mid-luteal phase of a NC are similar to those in a MNC. However, progesterone levels in one cycle only moderately agree with those in a next cycle.

Limitations, reasons for caution

Our data were obtained from women who had at least two frozen embryo transfer cycles and therefore may include progesterone levels different from those in good prognosis patients who got pregnant after a fresh embryo transfer or after a first frozen embryo.

Wider implications of the findings

Our data indicate that the moderate agreement of progesterone between cycles would imply assessment of progesterone in each cycle. In daily clinical practice, luteal phase support should be considered once a single progesterone measurement is below earlier described cut off levels predictive of ongoing pregnancy after frozen embryo transfer.

Trial registration number

not applicable