The Outcome of Two Protocols Used to Prepare Endometrium for Frozen Embryo Transfer

Receptive endometrium and a good quality embryo at the blastocyst developmental stage are prerequisites for a successful implantation to occur. Blastocyst freezing techniques and survival have witnessed huge improvements in the last years. Trials to improve the outcome of frozen embryo transfer (FET) are not to be stopped. The transfer of a good quality blastocyst represents a vital part of the process. Optimization of endometrial receptivity and implantation is an everlasting challenge.

Hormone replacement therapy (HRT) is now proven to be successful for preparation of the endometrium to receive the vitrified warmed embryos. Most HRT protocols give estradiol (E2) first to reach a satisfactory endometrial thickness, then followed by progesterone to mimic the natural cycles. E2 is mostly given for 10 to 14 days and this duration might be prolonged to reach a satisfactory endometrial thickness without adversely affecting the outcome. Trans-vaginal ultrasound assessment of the endometrial thickness before the start of P supplementation has been traditionally used to predict FET cycle outcome. Clinical pregnancy rates (CPR) and live birth rates (LBR) were found to decrease for each millimetre of endometrial thickness below 7 mm. Endometrial thickness however of 9 mm was reported to be among major factors affecting LBR after FET in a large set of data.

Further, there is a recent concept that endometrial compaction (decreased thickness) between the end of estrogen phase and the day of ET has favorable impact on the outcome of FET. Different modalities were proposed to enhance endometrial compaction. One of these modalities was to decrease the dose of estrogen so as to change the estrogen- progesterone ratio as well as help in preventing further endometrial growth.

Aromatase inhibitor (AI) can be used to decrease estrogen before starting P supplementation. Additionally, there were also reports that their use had been associated with improved implantation. It appears interesting to combine the easy scheduled HRT protocol with aromatase inhibitor to maximize FET outcome.

This proposed protocol has not been tested before. In current study, HRT plus AI will be compared with HRT only. In both groups, daily intramuscular P will be given for luteal support as it was shown to give the highest ongoing pregnancy rate in FET cycles.

We did a secondary follow up analysis of some exploratory outcomes (not preregistered). These outcomes were analyzed after publication and they include Live birth rate, implantation rate, hypertensive disorders of pregnancy, large for gestation and congenital anomalies. The results of these outcomes are planned to be presented elsewhere. For openness and transparency, we felt the importance to report this follow up in the registry.

Inclusion criteria

Inclusion criteria:

• Women aged from18 - 37 years old undergoing FET using good quality blastocysts vitrified on day 5(3 BB and more) (according to Gardner and Schoolcraft 1999) (8).
• Participants having at least one good quality blastocyst (3BB and more) available for transfer after warming.
• Participants having trilaminar endometrium of 9 mm after E2 preparation.

Exclusion criteria

• Women younger than 18 or older than 37 years old.
• Women who have uterine abnormality or pathology.
• Women who will not meet the inclusion criteria.
• Women who will refuse to participate in in the study.