P-607 Interindividual variation of progesterone elevation post LH rise: Implications for natural cycle frozen embryo transfers in the individualized medicine era.
Authors: Coughlan C 
Published: June 2023

Abstract

Study question
To what extent does the period between LH-rise and P4-rise vary in ovulatory natural menstrual cycles?

Summary answer
Three distinct ovulatory patterns were noted defined as the period between LH-rise and P4-rise and varied by up to two days.

What is known already
The key to success of FET in a NC is the accurate diagnosis of ovulation to determine the optimal timing of embryo transfer. The most common method used to determine time of ovulation in NC is the detection of luteinizing hormone (LH) surge. It is well recognized that the endocrine profile of menstrual cycles varies not only amongst women but also from cycle to cycle for any given female. Most hormone trajectories in individual women differ considerably from the mean hormonal curves and LH surges culminating in ovulation appear to be highly variable in timing, amplitude and duration.

Study design, size, duration
Retrospective, observational study including 102 women who underwent endocrine monitoring during a frozen embryo transfer in a natural cycle between 1st January 2017 and 31st August 2021 in a tertiary IVF centre.

Participants/materials, setting, methods
Ultrasound scans were performed to monitor follicular growth. Serial measurements of serum LH, FSH, estradiol and P4 were commenced once a dominant follicle measuring ≥ 14mm was identified and on three consecutive days until (including) the day of ovulation. The LH surge was considered to have begun when the concentration rose by 180% above the most recent serum value. Progesterone concentrations of 1.0ng/ml and above were regarded as confirmation of ovulation to schedule FET.

Main results and the role of chance
Patients’ characteristics presented as median and (range): age 35 years (23-43), BMI 25.24kg/m2 (17.32-38.21), AMH 2.07 ng/ml (0.06-8.12). Twenty-one (20.6%) women had the LH-rise 2 days prior to P4 -rise, 71 (69.6%) had on the day immediately preceding and 10 (9.8%) on the same day of P4-rise. If FET was scheduled based on LH-rise, 30.4% of the patients would have their FET scheduled on a different day than FET scheduled according to P4-rise. The period between LH-rise and P4-rise would be approximately one day longer in 20.6% of the participants and one day shorter in 9.8% than the anticipated 24 hour period. There was a significant difference in body mass index between those women who had LH-rise 2 days prior to P4-rise (BMI 26.91 kg/m2 (range 23.74-30.75) and the women who had LH-rise on the same day (BMI 22.39 kg/m2 (range 20.91-24.96) (p = 0.03). The AMH levels were also found to be significantly lower in those women who had LH rise 2 days prior to P4-rise ( AMH 1.59 ng/ml (range: 0.82-2.09) as compared to those who had LH-rise on the same day (AMH 2.67ng/ml (range: 1.83—6.63) (p = 0.04). LH may not serve as the best benchmark to schedule FET.

Limitations, reasons for caution
Frozen embryo transfers were scheduled according to serum progesterone levels therefore our study does not provide a direct answer to the question whether FET scheduled according to serum progesterone levels provides higher live birth rates than FET scheduled based on urinary or serum LH levels in a natural cycle.

Wider implications of the findings
Variation in the period between LH rise and progesterone rise in ovulatory cycles has implications for the choice of marker for the start of secretory transformation in frozen embryo transfer cycles. The study participants are representative of the relevant population of women undergoing frozen embryo transfer in a natural cycle.

Trial registration number
Not Applicable