O-112 Outcomes of random-start ovarian stimulation protocols as a possible evidence of the theory of antral follicles continuous recruitment
Authors: Martirosyan Y , Nazarenko T , Birukova A , Dmitrieva I 
Published: August 2021

Abstract

Study question
We tried to validate the possibility and efficiency of ovarian stimulation (OS) started on any day of the menstrual cycle, based on a theory of continuous recruitment of antral follicles.

Summary answer
Formation of a pool of follicles with higher sensitivity to gonadotropic stimulation occurs several times during the menstrual cycle (MC).

What is known already
According to classical concepts and fundamental positions formulated in the middle of the last century, follicular recruitment occurs only once during the menstrual cycle - in the early follicular phase. Nowadays there is increasing evidence to suggest that there are multiple (two or three) antral follicular waves of recruitment during the MC. Also some researchers state that the process of follicle recruitment is continuous.

Study design, size, duration
This prospective clinical study was conducted at the V.I. Kulakov NMRC for OG&Pof Russia. The study included female cancer patients seeking retrieval and cryopreservation of oocytes and/or embryos before cancer treatment. 240 patients were selected for the study. The patients were divided into 5 groups depending on the cycle day on the moment when ovarian stimulation was initiated. All patients signed an informed consent form approved by the Ethics Committee.

Participants/materials, setting, methods
The 1st group consisted of patients who started standart OS from 1 to 5 days of the cycle (n = 65); the 2nd - from 6 to 10 (n = 36), the 3rd - from 11 to 15 (n = 45), the 4th - from 16 to 22 (n = 44), the 5th - from 23 to 28 (n = 50). In the late follicular and luteal phase we performed OS without a pituitary modulator. The comparative analysis included features of oo-, embryogenesis and steroidogenesis.

Main results and the role of chance
The mean age, BMI and AMH were not different among groups. There were no LH rise or OHSS signs noticed in any groups, despite that OS in late follicular and luteal phase of the MC was performed with no GnRH antagonist addition.There was no statistically significant difference in the duration of stimulation, starting doses, total dose of FSH and HMG. The largest number of oocyte cumulus complexes was obtained in the 5th group (11 (9–21) vs 7 (3,5–15,5) in the 1st group, p = 0,030). The greatest number of mature oocytes was obtained in the 4th and 1st groups. In the 2nd group the largest number of immature oocytes was obtained (37 (9.1%)). A smaller number of mature oocytes (165 (61.8%) vs 492 (72.9%) and 314 (77.5%), p = 0.001) was obtained in group 2 (compared with the 1st and the 4th groups), when stimulation was started in the presence of a dominant follicle . These periods coincided with higher estradiol and lower FSH serum levels. Based on our data the optimal moment for effective OS initiation starts with the decrease in serum estradiol which is approximately 48 hours before the menstrual bleeding.

Limitations, reasons for caution
The presented results could be applied mainly to young patients with high and normal ovarian reserve, who were in the main study group. In patients with low ovarian reserve, short menstrual cycle and early ovulation an issue of favorable time points for the initiation of OS should be resolved individually.

Wider implications of the findings
The data collected during our research could possibly contribute to future personification of OS protocols. Tailoring the ovarian stimulation protocols to the needs of the patients could decrease time needed for completing the protocol without affecting oocyte yield or their maturity.

Trial registration number
none