P-670 The impact of fixed day-one versus day-six progestin initiation on ovarian response following progestin primed ovarian stimulation
Authors: Ferreira de Castro L , Santos-Ribeiro S , Guzman P , Nunes S , Soares S , Neves A  R 
Published: July 2024

Abstract

Study question
Does ovarian response differ between a fixed stimulation day (SD) 1 and SD 6 progestin start in a progestin primed ovarian stimulation (PPOS) protocol?

Summary answer
Fixed SD 1 and SD 6 PPOS protocols showed no significant differences in terms of ovarian response to stimulation.

What is known already
Ovulation prior to oocyte retrieval is a potential concern during ovarian stimulation (OS). Progestins, when compared to GnRH analogues, also effectively prevent premature ovulation with the added convenience in terms of its oral administration and lower costs. For this purpose, progestins may be started immediately with OS (SD 1) or later in the cycle, usually around SD 6, when the risk for ovulation increases. While the latter approach may be associated with a lower follicle growth suppression, evidence regarding the impact of the two protocols on ovarian response is still lacking.

Study design, size, duration
We conducted a single center retrospective cohort study in a private fertility clinic, including 923 patients (584 in the SD1 group and 339 in the SD6 group) who underwent 1064 OS cycles (652 in the SD1 group and 412 in the SD6 group) using a PPOS protocol between January 2016 and May 2023. Among these, 394 (37.03%) were oocyte donation cycles, 341 (32.05%) were autologous IVF/ICSI cycles and 329 (30.92%) were autologous vitrification cycles.

Participants/materials, setting, methods
We included women under the age of 44 who performed an OS cycle following a PPOS protocol. LH peak suppression was performed with daily desogestrel 75µg started either on SD 1 or on SD 6. The number of oocytes retrieved, number of mature (MII) oocytes, follicle-to-oocyte index (FOI) and follicular output rate (FORT) were compared between the groups. Comparisons are presented as adjusted regression coefficients (β) and 95% confidence intervals (95%CI) following multivariable linear regression.

Main results and the role of chance
The majority of patients in the SD1 group were donors (59.66%), while in the SD6 group most patients were doing assisted reproductive techniques (ART) with autologous oocytes (98,78%). In the SD1 group, patients were older (38.93±3.81 vs. 37.93±4.00, p &lt; 0.001), had a higher antral follicle count (AFC) (20.79±8.66 vs. 14.12±9.96, p &lt; 0.001), underwent OS with a lower gonadotropin dose (2036.25±766.20IU vs. 2715.20±976.40IU, p &lt; 0.001) and triggered mostly with GnRHa (86.44% vs. 57.50%, p &lt; 0.001). Both groups presented a similar body mass index (BMI) (22.80±2.96 vs. 21.71±3.25kg/m2, p = 0.175). Bivariate analysis revealed a higher number of oocytes retrieved (19.40±12.02 vs. 10.10±8.19, p &lt; 0.001), number of MII oocytes (12.05±5.97 vs. 7.42±5.91, p &lt; 0.001), FORT (81.53±20.59% vs. 73.72±23.80%, p &lt; 0.001) and FOI (95.49±48.78% vs. 76.31±47.60%, p &lt; 0.001) in the SD1 group. No difference was found in the cancellation rates among the two groups (1.99% for SD1 vs. 3.16% for SD6, p = 0.322).
Following adjustment for age, BMI, AFC, ART treatment, type of trigger and total gonadotropin dose, no difference was found regarding the number of oocytes retrieved (β=-0.62; 95%CI -2.53 to 1.30), number of MII oocytes (β=-1.66; 95%CI -3.43 to 0.10), oocyte maturation rate (β = 2.30; 95%CI -4.60 to 9.20), FOI (β=-3.29; 95%CI -13.15 to 6.57) or FORT (β=-1.78; 95%CI -5.66 to 2.10).

Limitations, reasons for caution
Despite attempting to mitigate confounding effects through multivariable linear regression analysis, the retrospective nature of the study and limited sample size may still be insufficient to eliminate bias. Moreover, reproductive and perinatal outcomes were not reported.

Wider implications of the findings
Our study suggests that both the SD1 and SD6 PPOS protocols can be employed based on patients’ and clinicians’ preference, regardless of the type of ART treatment or patient’s ovarian reserve, without impact on ovarian response to stimulation.

Trial registration number
not applicable