P-618 Morning or evening start of exogenous progesterone five days before blastocyst transfer does not have an impact on ongoing pregnancy rates in artificial cycles.
Authors: Labarta E , Rodriguez-Varela C , Salvaleda M , Bosch E 
Published: June 2023

Abstract

Study question
Does morning or evening start of exogenous progesterone five days before a blastocyst transfer have an impact on pregnancy rates in artificial cycles?

Summary answer
Ongoing pregnancy rate is comparable when exogenous progesterone is started either in the morning or evening on the first day of progesterone exposure before ET.

What is known already
Luteal phase support (LPS) with exogenous progesterone (P) is mandatory in artificial cycles due to the absence of corpus luteum. The time of P exposure needed to optimize the outcome remain uncertain. Some endometrial receptivity tests claim for individualization of duration of LPS before ET to optimize the implantation potential of the embryo. As routine practice, 5 days of P exposure are needed for a blastocyst transfer in general population, but it is not clear yet if exogenous P has to be started in the morning or evening of the first day of P administration.

Study design, size, duration
Single-centre retrospective cohort study of 6493 artificial cycles for blastocyst transfer between December 2018 and July 2022. Endometrial preparation was performed with oestrogens and LPS with micronized vaginal progesterone (400 mg/12h MVP). LPS was given from five days before blastocyst transfer. Ongoing pregnancy rate (&gt;12w) was analysed according to the moment of starting progesterone (morning or evening) and hours of P exposure.
Cases in which LPS duration was different to 5 days were not included.

Participants/materials, setting, methods
Infertile patients undergoing ET in artificial cycles. Until March 2021, exogenous P was started in the evening of day 0 of P exposure (“evening start”); since April 2021, P was started in the morning of day 0 (“morning start”), before blastocyst ET. ET are performed between 12 and 18pm.
Serum P was measured at the time of ET (+2h). Routinely, patients with suboptimal P levels were added subcutaneous P (25mg/day) from the day of ET.

Main results and the role of chance
LPS was started in the evening in 3993 patients and in the morning in 2500 patients, all started five days before ET. Of note, there were no differences in these baseline/cycle characteristics: age, BMI, serum P in the proliferative phase, mid-luteal serum P, oocyte origin, EMT, number of embryos transferred. Patients with morning start had a significantly higher estradiol level (320.4 pg/mL vs 282.2pg/mL, p = 0.001).
Mean number of hours of P exposure until ET was 113.8 + 2.1h after evening start of MVP and 125.5 + 2.1h after morning start, p = 0.000. The minimum was 108.2 hours and maximum of 132.9 hours of P exposure.
Quartiles of P exposure (hours) before ET were: Q1:113.2h, Q2:115.8h, Q3:124.7h. No differences in OPR were observed according to these quartiles (&lt;Q1:47.4%; Q1-Q3:45.7%; &gt;Q3:47.1%, p = 0.46).
Likewise, evening or morning start of LPS did not exert any impact either in OPR (46.2% vs 46.8%, p = 0.65) or clinical miscarriage rate (17.2% vs 18.1%, p = 0.53). Binary logistic regression showed no differences in OPR (aOR (95%CI): 0.96 (0.85-1.09; p = 0.52) after adjusting for potential confounding variables.
Suboptimal mid-luteal P levels were observed in 23% (evening) vs 19.4% (morning start) of patients (p = 0.01). Having low P didńt impact on OPR (45.7%vs46.7%, p = 0.55) as rescue treatment was performed.

Limitations, reasons for caution
The limitation is the retrospective study design, although sample size is large enough to draw conclusions and control for potential confounding factors. Moreover, study period was different in both groups, although protocols and general results were comparable. If these results are similar in other ways of P administration, remains unknown.

Wider implications of the findings
These findings suggest that a difference of 12 hours in the initiation of exogenous P does not impact on the cycle outcome in artificial cycles as far as it is started 5 days before ET. Thus, LPS can be started either in the morning or evening without hampering the results.

Trial registration number
not applicable