P-369 An innovative approach for FET that does not rely on the luteinizing hormone surge or human chorionic gonadotropin: a natural cycle with luteal support
Authors: Dudenko Lozenko D , Pau E , Teruel J , Fortuño S , Caroppo N , Crespo J 
Published: June 2023

Study question

Can progestin supplementation in natural cycle, without reliance on LH surge or hCG ovulation triggering, effectively prepare the endometrium for a frozen embryo transfer (FET)?

Summary answer

High pregnancy rates can be achieved in natural cycle using luteal support as the main method for endometrial synchronization, without relying on the LH surge

What is known already

In recent years, frozen-thawed embryo transfer has become widely adopted and plays a significant role in assisted reproductive technology. To date, the evidence suggests that natural cycles result in higher pregnancy rates and fewer obstetric complications compared to hormonal replacement therapy, however, the most effective method for preparing the endometrium has not yet been determined.

For transfer in the natural cycle specifically, conflicting results have been reported in terms of the outcome following spontaneous or triggered ovulation. No research is available that supports a natural cycle FET without monitoring the endogenous LH surge or using hCG trigger.

Study design, size, duration

This is a prospective analysis of 508 natural FET cycles between March 2019 and December 2022, including patients receiving embryos with own oocytes (339) and donated oocytes (169).

Participants/materials, setting, methods

All patients underwent ultrasound monitoring and serum hormone levels determination of estrogen and progesterone in 3 moments of the cycle (the day of the start of luteal support, 1 week before B-HCG and the day of B-HCG). Upon ultrasound confirmation of the endometrium's optimal thickness and appearance and the presence of the pre-ovulatory follicle, patients began progesterone supplementation and the day for FET was scheduled.

Main results and the role of chance

A clinical pregnancy rate of 65.48% was reported with a miscarriage rate of 9.09%.

A higher rate of miscarriage (22.22%) was found to be associated with an endometrial thickness of less than 7mm at the time of progesterone initiation. The size of the dominant follicle did not affect pregnancy outcome, but a higher pregnancy rate was observed when the follicle measured 15 mm or larger (CPR of 66.83% in cycles with a follicle ≥15mm versus CPR of 60.22% in cycles with a follicle &lt;15mm). Estrogen levels decline in the second measurement but increase again on the day of a positive beta test.

This protocol requires less monitoring compared to true and modified natural cycles and is convenient to coordinate with oocyte recipients. A thin endometrial lining, measured below 7mm, increases the risk of a clinical miscarriage. A lack of increase in estrogen levels on the day of B-hCG is an unfavorable sign for a positive outcome.

Limitations, reasons for caution

Our analysis of data has a prospective design, although it may be limited by unmeasured factors such as the number, stage, and chromosomal testing of transferred embryos.

Wider implications of the findings

Supplementary luteal support does not affect the natural progression of the endometrium towards receptiveness and results in a key intervention for controlling the start, length and functionality of the window of implantation. A natural cycle, with progesterone supplementation but without monitoring the LH surge, results in high pregnancy rates.

Trial registration number

Not applicable