What is the best preparation method for frozen embryo transfer?

This study compared three methods of preparing the uterine lining prior to frozen embryo transfer (FET). It found that modified natural cycles may have higher pregnancy rates than either fully natural cycles or artificial hormone replacement.

FET involves transferring an embryo which was frozen after in vitro fertilization (IVF). FET can increase the total pregnancy rate per IVF egg collection, and reduce the risk from transferring multiple embryos.

The lining of the uterus must be receptive to embryo implantation when the FET is done. In a natural menstrual cycle, the uterine lining develops under the influence of the hormone estrogen. After ovulation, the hormone progesterone causes the uterine lining to mature in preparation for implantation. Natural cycle (NC) uses ultrasound and/or hormone tests to time FET for the receptive phase after ovulation. Modified natural cycle (mod-NC) uses a hormone injection to trigger ovulation prior to FET. Artificial replacement (AR) uses estrogen and progesterone medications to grow and mature the uterine lining. At most fertility centers, NC and mod-NC are only offered to women with regular menstrual cycles.

It is not clear which preparation method leads to the best FET results.

This study used records of 2,895 FET cycles from a single fertility clinic. All cycles transferred a single embryo. 561 cycles used NC, 1,749 used mod-NC, and 585 used AR. For NC, ultrasound, and at-home tests of urinary luteinizing hormone (LH) were used to monitor the cycle. If the dominant ovarian follicle reached a mature size (16 – 20 mm) without an LH surge, then the patient was transferred to a mod-NC protocol and a trigger injection was given. Patients using AR were given estrogen (estradiol valerate; Progynova) from the start of menstrual bleeding until the uterine lining became at least 7 mm thick. Patients were then given progesterone (Prometrium).

Patients using AR were significantly more likely to have polycystic ovarian syndrome (PCOS) than those using mod-NC (23.93% vs. 6.75%). At the same time, patients using AR had higher ovarian reserve (anti-Mullerian hormone of 5.12 vs. 3.31 ng/mL)

Mod-NC cycles had the highest rate of pregnancies observable on ultrasound (43.05%). This was significantly higher than the rate for NC (32.62%). This rate was 37.26% in the AR group. AR had the highest rate of miscarriage (27.52% vs. 19.67% NC, 19.39% mod-NC). The live birth rate with mod-NC (33.56%) was significantly higher than the other two methods. NC (24.06%) and AR (25.81%) had similar birth rates.

This study found that patients using mod-NC had a higher pregnancy rate than those using NC or AR for FET.

Which treatment to use was determined by the patient’s medical history and whether she developed an LH surge soon after an ovarian follicle developed. The three groups of patients did not have the same characteristics, which may influence the results.