In the past, study-related limitations have prevented systematic reviews and meta-analyses from determining which endometrial preparation methods for FET were most effective in terms of pregnancy success [[1], [2], [3]]. The effectiveness of the endometrial preparation method, including the luteal phase support (LPS) regimen and transfer timing protocol, is critical because embryo and endometrium contribute equally to pregnancy success [4,5].
The decision by clinicians and IVF centres to increase their use of FET was probably based primarily upon the increased pregnancy rates achieved with the use of the improved assisted reproductive technologies introduced in FET [[6], [7], [8]]. Published reports from the European IVF-monitoring Consortium, Centres for Disease Control and Prevention, and Australia and New Zealand Assisted Reproduction Database (2001–2020) showed that since 2012 the delivery rate per FET cycle has bypassed the delivery rate per fresh ET cycle in the USA and Australia and New Zealand [7]. The more physiological and modifiable nature of luteal phases (LP) has also supported the preferred use of FET, with LPs in fresh ET nearly always adversely affected by ovarian stimulation (OS) [4,9,10].
The primary categories of endometrial preparation methods used in FET include natural (N), artificial (A), and stimulated (S) methods, with the ovulatory status of patients, as well as the impacts on patients (i.e., inconvenience, cost, discomfort, side-effects, and treatment duration) and clinics (i.e., workload) determining the method used [11]. In survey studies conducted globally, a preference to use the physiologically compromised (i.e., absence of corpus lutea] AC method has been reported by most participants [8,11,12]. Moreover, while methodological and procedural advantages were the main reasons for the preferred use of the AC method, the preference was also driven by the complexities associated with the NC method (i.e., uncertainty in day-of-ovulation prediction and reduced flexibility and predictability in the planning and scheduling of transfer) [2,5,11].
In a more recent systematic review and network meta-analysis of endometrial preparation methods used in FET, the AC-FET method was ranked last, with this method having the lowest LB and highest pregnancy loss rates [13]. The evidence of increased pregnancy loss, therefore, raises the question of whether the AC method should be preferred, as the ramifications of pregnancy loss may outweigh its advantages [14,15]. The objective of the present study was to compare the efficacy of AC-FET with that of NC-FET in terms of ongoing pregnancy and pregnancy loss, with intensive method-specific LPS administered in the FET methods.
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