What is the optimal means of preparing the endometrium in frozen–thawed embryo transfer cycles? A systematic review and meta-analysis

Abstract

BACKGROUND Frozen-thawed embryo transfer (FET) enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred at a later date. In recent years the number of FET cycles performed has increased due to transferring fewer embryos per transfer and improved laboratory techniques. Currently, there is little consensus on the most effective method of endometrium preparation prior to FET. METHODS Using both MEDLINE and EMBASE database a systematic review and meta-analysis of literature was performed. Case-series, case-control studies and articles in languages other than English, Dutch or Spanish were excluded. Those studies comparing clinical and ongoing pregnancy rates as well as live birth rates in (i) true natural cycle FET (NC-FET) versus modified NC-FET, (ii) NC-FET versus artificial cycle FET (AC-FET), (iii) AC-FET versus artificial with GnRH agonist cycle FET and (iv) NC-FET versus artificial with GnRH agonist cycle FET were included. Forest plots were constructed and relative risks or odds ratios were calculated. RESULTS A total of 43 publications were selected for critical appraisal and 20 articles were included in the final review. For all comparisons, no differences in the clinical pregnancy rate, ongoing pregnancy rate or live birth rate could be found. Based on information provided in the articles no conclusions could be drawn with regard to cancellation rates. CONCLUSIONS Based on the current literature it is not possible to identify one method of endometrium preparation in FET as being more effective than another. Therefore, all of the current methods of endometrial preparation appear to be equally successful in terms of ongoing pregnancy rate. However, in some comparisons predominantly retrospective studies were included leaving these comparisons subject to selection and publication bias. Also patients' preferences as well as cost-efficiency were not addressed in any of the included studies. Therefore, prospective randomized studies addressing these issues are needed.

The state of “freeze-for-all” in human ARTs

“…A systematic review and meta-analysis published in 2013 compared clinical and ongoing pregnancy rates, as well as live birth rates, in (a) true natural cycle FET (NC-FET), (b) modified NC-FET with hCG, (c) artificial cycle FET (AC-FET), and (d) AC-FET supplemented with GnRH agonists. The study revealed no significant advantage of any specific approach to prepare the endometrium for FET in terms of clinical pregnancy rates or live birth rates [75]. The results were in line with the previous systematic review published in 2008 [76].…”

Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles

“…In a recent review and meta-analysis, no single endometrial preparation method for FET was found to be superior, with all methods being equally effective in terms of ongoing pregnancy [16]. The connecting protocol, therefore, needs to maintain the existing cost-effectivity and predictability of treatment without compromising reproductive outcome.…”

“…On the 14th day of estrogen therapy a transvaginal ultrasound scan (TVUS) was performed to measure endometrial thickness. An endometrial thickness of >7 mm was considered most optimal [16,22]. On the day of scan, serum progesterone was also measured, with FET cycles cancelled if the serum progesterone concentration was above an arbitrary chosen threshold (2 ng/mL).…”

“…Based on these concerns, it was decided to continue the use of artificial cycle (AC) FET for all cycles, even though natural cycle (NC) FET could be considered to be simpler it would, however, decrease predictability-even in the regularly cycling patient-and increase patient clinic interaction. Importantly, in a recent meta-analysis, Groenewoud et al [16] found that all types of FET protocols (i.e., NC, modified-NC, AC, and modified-AC) were equally successful in terms of ongoing pregnancy.…”

Optimal parameters for determining the LH surge in natural cyclefrozen-thawed embryo transfers

“…Additionally, FET after cryopreservation of all embryos has been widely used either to perform preimplantation genetic screening (PGS) or to minimize the risk of developing ovarian hyperstimulation syndrome (OHSS) [2]. FET can be accomplished with various endometrial preparation protocols including programmed cycles involving the use of exogenous estrogen and progesterone, or using the patient's natural cycle and associated endogenous hormones [3]. NC-FET is considered by many clinicians the preferred method for women with regular ovulatory menstrual cycles because it does not require long-term exogenous hormonal replacement [4].…”