P-259 Luteal phase in dual stimulation. Do we have the same outcomes in morphokinetics, laboratory, clinical and genetic parameters?
Authors: Boyano Rodríguez B , Herrero Grassa L , Aparicio González M , Cascales Romero L , Bravo Martín R , García Roa A , Arias Jiménez L  G , Ortiz Salcedo J  A , Ten Morro J , Bernabeu García A , Bernabeu Pérez R  F 
Published: July 2024

Abstract

Study question
Do luteal phase (LF) embryos have the same outcomes in laboratory and morphokinetics parameters and clinical and genetic rates that follicular phase (FF) embryos?

Summary answer
Laboratory outcomes, ploidy and clinical rates result similar between two phases. In morphokinetic analysis we obtained significant differences in the duration of visible pronuclei.

What is known already
Dual stimulation (DS) protocols are being proposed as a useful strategy in patients with poor prognosis, particularly in cases of low response or low ovarian reserve. Nevertheless, there is still a lack of solid evidence for their use. In this context, it is interesting to analyse if the embryos from the LF achieve the same results as those from the FF. Our previous studies have shown comparable data, although they included vitrified oocytes. To avoid the impact of vitrification, we only review those cycles with fresh oocytes. A morphokinetic analysis is also added to compare their development.

Study design, size, duration
This multicentre retrospective evaluated 81 cycles of DS and PGT-A in patients with some poor prognostic feature (Antimüllerian hormone &lt;1ng/ml, antral follicle count &lt;6, poor response, &gt;39 years) with 161 pick-ups between January 2022-August 2023 (81 in FF and 80 in LF). A total of 398 embryos were biopsied (195 from FF and 203 from LF) and 59 frozen embryo transfers were performed (33 in FF and 26 in FL) between January 2022-December 2023.

Participants/materials, setting, methods
We compared several parameters between the two groups including gamete age, oocyte number, MII number, fertilization rate, blastocyst quality, biopsy rates, and genetic results. Additionally, clinical outcomes after embryo cryotransfer were also studied. We compared classical morphokinetic parameters as well. We performed this preliminary analysis on 226 embryos (99 FF, 127 LF) in two ways: comparing FF and LF embryos as two groups and comparing by patient within the same cycle in a paired analysis.

Main results and the role of chance
The average age of the patients was 40.5 (±2.3). No significant differences were found in terms of oocytes retrieved per patient (8.7 ±4.9 vs 9.2±5.9), maturity (7.2 ±4 vs 7.7±4.3) or number of embryo biopsied (6.54 ±3.9 vs 6.9±4.4). After genetic analysis, euploidy rate was found to be lower in LF compared to FF although not statistically significant (23.6% and 28.6%). Aneuploidy (67.4% vs 71.4%) and mosaicism rates (22.3% vs 19.1%) were also comparable between the two groups. In the same way, we did not find any statistically significant differences in the day of transfer, quality of the embryo transfer, neither pregnancy rates (54.5% vs 50%) nor life birth rate (54.5% vs 38.5%). In the preliminary morphokinetic analysis we only obtained significant differences in the time in which pronuclei were visible, being greater in the FF (16±3h vs 15±3h, p = 0.005/p=0.004 after adjusting for confounding variables). In addition, it appears that the pronuclei of the FF embryos tend to take longer to disappear. Also, these FF embryos complete the third cell cycle in a slower way than LF embryos, although none of these comparisons are statistically significant (p = 0.065 and p = 0.068). In the paired analysis we didn’t find any statistically significant difference.

Limitations, reasons for caution
This study is limited by its retrospective nature. Validation by a prospective study is recommended. Regarding morphokinetics, it is necessary to increase the number of embryos analysed to increase the statistical power of the study.

Wider implications of the findings
It is interesting to analyse LF embryos’ morphokinetics since there are few studies in this regard. Moreover, it is still unclear whether the oocytes obtained from the LF cycles are the result of the second stimulation or a persist effect of the first one, which could somehow affect embryo development.

Trial registration number
Not applicable