Endometrial preparation protocols
In this study, different methods of endometrial preparation methods were non-selectively and consecutively recorded, and used exposure variables to observe the correlation with live birth rate and other clinical outcomes. The type of endometrial preparation was determined by the treating physician’s preference, based on patients’ characteristics. In general, women with regular ovulation were allocated to natural cycles (n=1676), while patients who were reluctant to frequently monitoring or living far from the hospital were allocated to artificial cycles (n=8057). The detailed protocols for NC and AC endometrial preparation were described as follows:
1) Natural cycles for FET
Follicle monitoring began on day 8-10 of the menstrual cycle. When the leading follicle reached a mean diameter of >17mm, serum luteinizing hormone (LH) was <20 IU/L, 10000 IU of human chorionic gonadotropin (hCG) was administered to trigger oocytes ovulation. Ovulation was confirmed by transvaginal ultrasound the day after hCG and the next day. When LH was >20 IU/L, transvaginal ultrasound was performed every day until ovulation.
Artificial cycles for FET
In women treated with AC, endometrial priming started on the fifth day of the menstrual cycle with estradiol valerate (Progynova; Bayer Schering Pharma AG, Berlin, Germany) orally administered at a dose of 6mg daily. After 10-12 days of endometrial preparation, transvaginal ultrasound and progesterone level were performed. In women with endometrial thickness >8mm and serum progesterone (P) level <1.5ng/ml, intramuscular progesterone at a dose of 60mg daily was administrated.
The timing of FET was based on the day of embryo freezing and the day of ovulation (i.e., 3 days after ovulation for cleavage stage embryos and 5 days after ovulation for blastocyst stage embryos). Triple-line endometrial pattern of endometrium was classified as pattern A (a triple-line pattern consisting of a central hyperechoic line surrounded by two hypoechoic layers), pattern B (an intermediate isoechogenic pattern with the same reflectivity as the surrounding myometrium and a poorly defined central echogenic line), and pattern C (homogenous, hyperechogenic endometrium)8.