The relationship between endometrial thickness and successful embryo transfer remains a matter of controversy. Sofia Makieva describes results from a large registry study which found that, while live birth rates decrease with endometrial thickness, reasonable outcomes were obtained with even lower endometrial thickness measurements.
An endometrial thickness of <8 mm for fresh and <7 mm for frozen embryo transfer may reduce the chance of pregnancy, although pregnancy can still be achieved even with a very thin measurement of 4 mm. These are the main findings of a registry study which analysed 21,914 fresh and 18,942 frozen embryo transfers recorded in the Canadian ART Registry between January 2013 and December 2015 and is said to be the largest retrospective study so far assessing the extent to which a thin endometrium on the day of ovulation trigger may jeopardise the occurrence of pregnancy – a topic of great controversy.(1)
Securing a receptive endometrium is essential for successful ET. Routine practice employs high-resolution ultrasonography to assess endometrial responsiveness, commonly on the day of ovulation trigger, by measuring, among other parameters, the thickness of endometrial lining. Many studies have tried to establish a cut-off value, with results ranging between 6 mm and 10 mm. However, according to the Canadian investigators the heterogeneity in these studies - with different stimulation protocols, various monitoring techniques, and diverse statistics - has meant persistent ambiguity surrounding the usefulness of endometrial thickness (EMT) measurement in predicting IVF outcomes.
In 2014 Kasius and colleagues performed a meta-analysis of 22 studies hitherto measuring EMT at ovulation trigger.(2) In a univariate analysis of 10,724 fresh IVF cycles, EMT lacked predictive capacity, although a cut-off <7 mm, occurring in 2.4% of the cases, was associated with a lower clinical pregnancy rate but not live birth rate. As a result, the authors concluded that the use of EMT in counselling is not justified. The advice to ignore EMT during IVF monitoring was backed up earlier this year by Griesinger’s retrospective analysis of data derived from two clinical trials (addressing a different topic).(3) The EMT of 1401 women was recorded, notably, on the day of transfer and only 5% of these had EMT <7 mm. The study found a significantly higher chance of ongoing pregnancy with EMT ≥9 mm but the predictive value was clinically insignificant in multivariate analysis.
The Canadian ART Registry is a unique cohort which includes fresh and frozen-thaw ETs, highly strengthened by its large size allowing stratification of EMT data per millimeter and, consequently, the observation of a gradual response. Thus, results showed that every millimeter drop in EMT below 8 mm in fresh and below 7 mm in frozen transfers resulted in a significant decrease in pregnancy and live birth rates. The LBR in the EMT ≥8 mm group was 33.7% in the fresh and 28.4% in the frozen ETs. Acceptable LBRs were noted even in the ambivalent EMT 4-5.9 mm groups: 25% for fresh and 16.8% for frozen ETs, which comprised just 1% and 0.6% of the population respectively.
Based on these results and the additional finding that women of 40 years or older were unlikely to achieve an EMT ≥8 mm, the authors suggest that a persistently thin endometrium should not be discouraging. They do, however, warn that this message should be interpreted with caution as their cohort included only cycles proceeding to ET. The latter is not to be taken lightly, as a good prognosis bias introduced to the cohort may downplay the negative impact of a low EMT.
Evidence-based IVF practice is coming to terms with the idea that interventions to correct EMT may be irrational. However, the low numbers of transfers in the presence of EMT <7 mm limits the power of statistics and consolidation of evidence. The CARTR authors thus call for a prospective study in which transfers are performed even in the presence of low EMT; this, they suggest, may eventually reassure physicians and couples facing the dilemma of a thin endometrium. Who shall take such risk though?
1. Liu KE, Hartman M, Hartman A, et al. The impact of a thin endometrial lining on fresh and frozen–thaw IVF outcomes: an analysis of over 40,000 embryo transfer
s. Hum Reprod 2018; 33: 1883–1888.
2. Kasius A, Smit JG, Torrance HL, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis
. Hum Reprod Update 2014; 20: 530-541.
3. Griesinger G, Trevisan S, Cometti B. Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome
. HROpen 2018; 1 January 2018, hox031.