Exploring the Optimal Endometrial Preparation Protocol for Frozen-Thawed Embryo Transfer

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Background

In recent years, with the significant improvement of ovarian stimulation regimens, embryo cryopreservation and thawing techniques, the frozen-thawed embryo transfer (FET) procedure has gained more popularity in assisted reproductive technology (ART) than fresh embryo transfer. In general, the success of FET depends on the quality of embryo, receptivity of uterine, and synchronization between embryo and endometrium. Therefore, it is of particular importance to determine the optimal timing to perform FET, known as the "window of implantation".

Currently, two types of endometrial preparation protocols are widely used in clinical practice. With oestradiol and progesterone supplemented exogenously, the artificial cycle (AC) is the most commonly used protocol in the world, since it enables IVF centers flexibility to regulate embryo transfers. Another protocol named natural cycle (NC) has become increasingly popular, where a physiological cycle is monitored. It can be "modified" by using human chorionic gonadotropin (hCG) to trigger ovulation and/or progesterone to support the luteal phase. In contrast, other protocols, such as those involving gonadotrophins, letrozole, or GnRH agonists, are less common. Performing FET in a spontaneous cycle is beneficial as it mimics the natural process and eliminates side effects associated with medication. Besides, it is significantly more affordable than hormone therapy in ACs. However, NC-FET may have disadvantages, such as the unpredictable timing of embryo transfers. In ACs, administration of exogenous oestradiol and progesterone may be beneficial, as it facilitates easy management and flexibility in the timing of the FET and minimizes cancellation rates. Despite all the talk, there is no consensus regarding using one protocol over another. Noteworthy, previous retrospective studies have found that AC-FET is associated with an increased risk of pregnancy loss and complications for both mother and fetus, yet prospective clinical trials are still needed to confirm these findings.

This Research Topic aims to find the optimal endometrial preparation protocol as well as the window of implantation in different populations.
We welcome submissions of all acceptable article types, particularly Original Research, Reviews, and Systematic Reviews, regarding the following sub-topics, including but limited to:
• Efficacy and safety of artificial cycles in patients with regular ovulation;
• In artificial cycles, the impact of unexpected dominant follicle development on pregnancy outcomes;
• Duration of estrogen exposure during artificial cycles and reproductive outcomes;
• Whether different methods of uterine withdrawal bleeding affect pregnancy outcomes before endometrial preparation in women with oligomenorrhea or amenorrhea;
• Stimulation cycles versus artificial cycles in patients with irregular ovulation including polycystic ovary syndrome (PCOS);
• Women with endometriosis, adenomyosis or recurrent implantation failure: clinical utility of GnRH-a hyperregulation coupled with artificial cycles;
• Clinical outcomes of natural cycle FETs with unintended nondominant follicles and unruptured luteinized follicles;
• Whether or not the natural cycle or modified natural cycle requires sufficient luteal phase support.

Keywords: window of implantation, frozen-thawed embryo transfer, artificial cycle, natural cycle, modified natural cycle

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