A systematic review and meta-analysis concluded that there is insufficient evidence to recommend one particular protocol for HRT with regard to pregnancy rates after frozen embryo transfer, and no comparison of estrogen dose or route of administration was included in the review[7]. It is worth highlighting that the authors did not find any literature discussing the effect of estrogen dose and route of administration for HRT on reproductive outcomes. In 2016, a retrospective cohort study concluded that there is no difference in live birth rates between a constant dose versus an increasing dose of estrogen in oocyte donation cycles with oral or transdermal supplementation[6]. In order to provide good evidence about pattern of estrogen supplementation in HRT-FET, a randomized controlled study is urgently needed.

The present randomized controlled study aims to compare between a constant estrogen dose protocol and a step-wise increasing estrogen dose protocol on the live birth rate of HRT-FET cycles.

The objective is to compare between a constant estrogen dose protocol and a step-wise increasing estrogen dose protocol on live birth rate of HRT-FET cycles.

This is a multicenter randomized controlled trial. Women undergoing HRT-FET will be recruited and randomized to use a constant estrogen dose protocol and a step-wise increasing estrogen dose protocol.

Participation in the study is totally voluntary. The subjects can withdraw from the study at any time and they will still receive standard medical care.

Women being scheduled for HRT-FET will be assessed for eligibility. Eligible women will be recruited in the study and each woman will only be included in the study once.

Informed written consent will be obtained prior to recruitment. The baseline characteristics will be collected. Transvaginal ultrasound will be done to measure the endometrial thickness on the day of progesterone supplementation. Embryo transfer will be performed 3 days or 5 days after progesterone use, depending on replacement of cleaving stage embryos or blastocysts respectively.

Inclusion Criteria:

• Women aged <42 years at the time of HRT-FET
• Replacing 1-2 early cleavage embryos or blastocysts after thawing.

Exclusion Criteria:

• Preimplantation genetic testing(PGT)
• Use of donor oocytes
• Hydrosalpinx shown on pelvic scanning and not surgically treated such as tubal ligation or resection
• Severe uterine adhesion
• The endometrial thickness cannot reach 8mm in previous fresh cycles or HRT -FET cycles

Until the completion of the study.