P-686 Optimal follicle size for triggering modified natural frozen embryo transfers
Authors: Maman E , Moran E , Luz A , Reuvenny S , Yitzhak N , Hourvitz R , Youngster M , Baum M , Hourvitz A 
Published: July 2024

Abstract

Study question
What is the optimal follicle size threshold for performing trigger in modified natural cycle frozen embryo transfers (mNC-FET) cycles

Summary answer
The optimal follicle size threshold for performing trigger is 16 or 17, depending on the clinic’s preference to risk too early or too late triggering

What is known already
Recent studies reported higher fetal and maternal obstetrical complication rates are observed in artificial cycles compared to natural cycle frozen embryo transfers (NC-FET), making the natural cycle (NC) the preferred method. The modified natural cycle (mNC) provides a partial solution to overcome the disadvantages of the NC, mostly its repeated visits and inability to conveniently schedule the transfer. In a recently published large RCT, pregnancy rates between NC and mNC were similar, but many patients allocated to the mNC group had an LH surge prior to the hCG injection.

Study design, size, duration
A retrospective study consisting of 5,862 NC-FET was performed between 2018 and 2023 in a large tertiary hospital.

Participants/materials, setting, methods
Statistical analysis was conducted to determine the optimal follicle size threshold for triggering, for each threshold between 12-20, under the following assumptions: Clinic is closed on Sundays, ultrasound is initially performed on day 8 of the cycle and every 2 days afterwards, trigger is performed if the follicle size is at or above the threshold, unless clinic is closed 2 days after the current test day in which case no trigger was given.

Main results and the role of chance
The analysis measured 2 main outcomes for each trigger size threshold:
The probability of triggering too early, defined as shifting the ovulation by 3 or more days.
The probability of spontaneous LH surge to occur before triggering, possibly leading to transfer cancelation due to clinic closure on the designated transfer day.
The traditional follicle size-based algorithm performed as follows:
[Follicle size threshold]: ] Early trigger probability], [Closed day transfer probability]
12: 71.9%, 0.1%
13: 61.7%, 0.1%
14: 49.0%, 0.2%
15: 33.9%, 0.6%
16: 21.3%, 1.3%
17: 12.9%, 2.8%
18: 7.3%, 4.5%
19: 3.4%, 6.7%
20: 2.2%, 8.6%
As can be seen from the results the optimal trigger threshold is either 16 or 17, depending on whether reducing transfers on days the clinic is closed has a higher importance than preventing a very early trigger day.

Limitations, reasons for caution
This was a retrospective study that performed statistical analysis to determine the probability of achieving each result based on the described logic. A prospective randomized clinical trial is warranted to validate the algorithm’s performance and consider variables that could not be accounted for, such as the patient’s endometrial width.

Wider implications of the findings
NC-FET protocols require the ability to adapt the transfer to clinics’ requirements. Given a traditional threshold-based methodology for triggering, a threshold of 16-17 is optimal depending on the risk preference of a clinic. Utilizing more advanced artificial intelligence algorithms based on ovulation prediction can significantly reduce both risk types.

Trial registration number
Not applicable