Personalized FET in RIF Patients With Displaced Dating

A Randomized Clinical Trial of Endometrial Histological Dating for Personalized Frozen-thawed Embryo Transfer (pFET) in Patients With Repeated Implantation Failure (RIF) in Natural Cycle

The endometrium becomes receptive as a result of a series of timed hormonal events during the menstrual cycle. The exposure of the endometrium to progesterone after ovulation initiates morphological and functional alterations that result in the change from a pre-receptive to a receptive endometrium. The morphological changes observed on histology for each specific day after ovulation were described by Noyes and his colleagues in 1950. An endometrial biopsy that shows a difference of more than 2 days between the histologic dating and actual day after ovulation is considered to be "out of phase" However, the clinical application of the Noyes criterion is relatively limited. We have verified the Noyes criterion in natural cycle in previous study which conducting endometrial biopsies respectively on day 3, 5, 7, 9 and 11 of post-ovulation (PO+3/5/7/9/11)(unpublished data). The clinical value of the endometrial histological dating in RIF patients in natural cycle is still to be answered. In this study, we tried to investigate the clinical effects of pFET in unexplained RIF patients according to the use of classic histologic endometrial dating to estimate the timing of the window of implantation and to adjust embryo transfer time in natural cycle.

Subjects in this group will be treated with personalized frozen-thawed embryo transfer. The blastocysts were delayed or advanced transferred after ovulation depending on the endometrium dating in RIF group

Subjects in this group will be treated with routine frozen-thawed embryo transfer.The blastocysts were transferred 5 days after ovulation regardless of endometrium dating in control group.

The blastocysts were delayed or advanced transferred after ovulation depending on the endometrium dating in RIF group

The blastocysts were transferred 5 days after ovulation regardless of endometrium dating in control group.

Ongoing pregnancy was defined as at least one intrauterine gestational sac with cardiac action by ultrasound performed 6 weeks after ET.

Inclusion Criteria: RIF patients (RIF is defined as the absence of a gestational sac on ultrasound at 5 or more weeks after 3 embryo transfers with high quality embryos or after the transfer of ≥10 embryos in multiple transfers); Out of phase dating patients; FET in natural cycle; Single blastocysts embryo transfer; Exclusion Criteria: 1. uterine abnormalities (double uterus, bicornuate uterus, unicornuate uterus and uterine mediastinum), intrauterine adhesions, endometriosis,adenomyosis, hydrosalpinx, and uterine fibroids (submucosal fibroids, non-mucosal fibroids> 4 cm and/or endometrial pressure);