P-609 Progesterone monitoring in fresh and frozen in assisted reproductive technique (ART) cycles - a Systematic review and Meta-analysis.
Authors: Lim Y C , Hamdan M , Maheshwari A , Cheong Y 
Published: June 2023

Abstract

Study question
What is the impact of serum progesterone monitoring in fresh and frozen ART cycles on live birth rates (LBR)?

Summary answer
There is no evidence of benefit that monitoring progesterone impacts LBR in fresh and FET cycles.

What is known already
Elevated progesterone (EP) during the follicular phase is postulated to cause detrimental effects on pregnancy outcomes by prematurely advancing the endometrium and affecting endometrial receptivity. In the luteal phase, optimisation of the supplementation of progesterone is in question. However, there has not been a consensus on the timing of monitoring or a threshold level to define an optimal progesterone level that leads to improved pregnancy outcomes.

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 63 studies (N = 57,586 women) for the meta-analysis. EP at baseline did not reveal any difference in LBR (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.39 to 1.49; I2 = 0%; 2 studies, 309 women; very low-quality evidence); EP on the day of trigger is associated with a reduction in LBR and CPR in various threshold, (LBR: P &gt; 1.0ng/ml, P &gt; 1.1ng/ml, P &gt; 2.0ng/ml, CPR: P &gt; 1.0ng/ml, P &gt; 1.1ng/ml, P &gt; 1.5ng/ml, P &gt; 2.0ng/ml) in studies which examined both D3 and D5 embryos. In studies including only D5 embryos, there was no difference in pregnancy outcomes between EP and NEP groups; LBR (P &gt; 1.5ng/ml, OR 0.96, 95% CI 0.81 to 1.14; I2 = 55%; 3 studies, 5,174 women; very low-quality evidence); CPR (P &gt; 1.5ng/ml, OR 0.90, 95% CI 0.78 to 1.04; I2 = 50%; 6 studies, 5,705 women; very low-quality evidence). We were unable to meaningfully meta-analyse studies examining EP at oocyte retrieval or during luteal phase in fresh cycle and EP at day before ovulation or during luteal phase in FET cycle.

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

Wider implications of the findings
There is no evidence that EP at baseline and at the time of ovulation trigger with D5 embryos impacts LBR. There is insufficient evidence that progesterone monitoring during day of oocyte retrieval, luteal phase in both fresh and frozen cycles impact LBR.

Trial registration number
PROSPERO (registration ID CRD42022382423)