Study question

Which is better for endometrial preparation method in frozen-thawed embryo transfer (FET) cycles, hormone replacement therapy (HRT) or ovulation induction with letrozole?

Summary answer

FET after ovulation induction with letrozole showed significantly higher ongoing pregnancy rates than FET after HRT in patients with polycystic ovary syndrome (PCOS)

What is known already

Frozen-thawed embryo could be transferred in natural cycle and HRT cycle. FET in natural cycle has several advantages like avoiding medication and painful injection. However, in case of patients with PCOS, embryos are usually transferred in HRT cycle due to menstrual irregularity. Letrozole gains popularity for ovulation induction in PCOS patients. It usually promotes single follicle development and exhibits no negative effect on endometrium. Therefore, it could be used for endometrial preparation of FET.

Study design, size, duration

This retrospective cohort study included 164 women with PCOS undergoing FET between Jan 2014 and Dec 2015.

Participants/materials, setting, methods

In letrozole group, patients were administered 5 mg letrozle per day from menstrual cycle day (MCD) 3. By ultrasound examination and monitoring of serum hormone levels, exact ovulation day was assessed. Cryopreserved day 3 embryos were transferred 3 days after ovulation.
In HRT group, patients were administered 6mg estradiol valerate from MCD 3. When endometrial thickness was above 8 mm, 50mg intramuscular progesterone was injected. Day 3 embryos were transferred 3 days after progesterone injection.

Main results and the role of chance

In each group, age, AMH level, number of transferred embryos and percentage of top quality embryos reflected no differences. Pregnancy rate of letrozole group showed increased tendency as compared with that of HRT group [55.6%(25/45) vs. 39.5%(47/119), P=0.094]. There was no significant difference between two groups in the spontaneous abortion rate [12.0%(3/25) vs. 29.7%(14/47), P=0.283].  Ongoing pregnancy rate was significantly higher in letrozole group [48.9%(22/45) vs. 27.7%(33/119), P=0.029].

Limitations, reasons for caution

This is a retrospective study. A prospective randomized study with large sample size would have minimized potential limitations.

Wider implications of the findings

FET after ovulation induction, patient-friendly endometrial preparation method without painful injection, showed significantly higher ongoing pregnancy rates than FET after HRT cycle. It suggests not only estrogen and progesterone but also another substance could affect implantation. Study about endometrium after HRT and ovulation induction could help better understanding about implantation.