Key message
In fresh embryo transfer cycles, a linear correlation exists between the entire range of pre-trigger endometrial
Many investigations have focused on factors predicting assisted reproductive technology (ART) outcomes. The most important primary factor associated with successful IVF is maternal age, which is associated with embryo euploidy (Kasius et al., 2014; Zhang et al., 2018). Other factors are the quality and quantity of the embryos available for transfer and endometrial characteristics, such as endometrial pattern, subendometrial blood flow and endometrial thickness (EMT) (Zhao et al., 2012; Kasius et al., 2014; Bu and Sun, 2015; Bu et al., 2016; Oron et al., 2018; Zhang et al., 2018).
Endometrial thickness is the most commonly used and significant indicator of endometrial receptivity (Bu et al., 2016; Zhang et al., 2018). It is routinely assessed during ovarian stimulation and on the trigger day in IVF cycles, and serves as the routine clinical gauge of adequate endometrial development (Al-Ghamdi et al., 2008), mainly because it is amenable to convenient and non-invasive measurement. Studies of the association between pre-trigger EMT and ART outcome, however, have yielded equivocal results (Bassil, 2001; Schild et al., 2001; Kovacs et al., 2003; Al-Ghamdi et al., 2008; Zhao et al., 2012; Kasius et al., 2014; Bu et al., 2016; Griesinger et al., 2018; Holden et al., 2018; Zhang et al., 2018), largely owing to their relatively small sample size and weak control of confounding factors, such as age and ovarian response, which affect EMT and are proven predictors of ART outcome. Moreover, most published studies have investigated the relationship between EMT and pregnancy rates but not between live birth rates or pregnancy outcomes. Thin endometrium, usually defined as 6 mm or less, is accepted as a negative predictive factor for pregnancy rates and outcomes in ART. It has been associated with implantation failure, decreased pregnancy rates, advanced maternal age and poor ovarian response (Weissman et al., 1999; Kasius et al., 2014; Holden et al., 2018; Oron et al., 2018). The effect of normal endometrium (≥7 mm) and thick endometrium (>13–14 mm) on ART outcome, and specifically the effect of thick endometrium on implantation and pregnancy rates, remain unclear (Weissman et al., 1999; Al-Ghamdi et al., 2008; Zhao et al., 2012; Bu et al., 2016; Holden et al., 2018). Some studies have shown that a thick endometrium poses an increased risk for miscarriage (Weissman et al., 1999), whereas others have found that thicker endometrium (>11 mm) is associated with positive pregnancy rates and outcomes (Holden et al., 2018).
The aim of the present study was, therefore, to investigate the association between the entire range of measurements of pre-trigger EMT with live birth rate (LBR) in a large cohort of fresh IVF and embryo transfer cycles. The EMT measurements were divided into subgroups of 3 mm each, for more accurate EMT stratification and comparison of EMT values among patient age and ovarian-response subgroups, to isolate the effect of EMT thickness from the effect of these known confounders.
A retrospective cohort study was conducted at the Infertility and IVF Unit of a tertiary university-affiliated hospital between January 2009 and December 2017. All IVF cycles with fresh day-3 embryo transfers in women aged 42 years or younger were included. This is the largest group of fresh embryo transfers carried out in our unit during the above period, so, for the purpose of embryo type uniformity, only day-3 transfers were included. Cases of pre-implantation genetic testing,
A total of 5133 fresh embryo transfer cycles, carried out in 2343 female patients, met the inclusion criteria. The overall LBR was 20.92%. The EMT measured 6 mm or less in 312 cycles (6.08%), 7–9 mm in 2114 cycles (41.18%), 10–12 mm in 2031 cycles (39.57%), 13–15 mm in 562 cycles (10.95%) and 16 mm or in 114 cycles (2.22%). The corresponding LBRs in these five groups were as follows: 11.22% (35/312), 17.98% (380/2114), 23.44% (476/2031), 25.62% (144/562) and 34.21% (39/114) (P <0.001) (Figure 1
The association between EMT and LBR in fresh IVF cycles is still unclear. In this large single centre cohort study, we identified a linear correlation between the entire range of trigger day EMT thickness measurements and LBR after fresh day-3 embryo transfers. This association was persistent even after stratification for age and ovarian response. Several studies reported a positive association of EMT with IVF outcomes, especially pregnancy rate (Kovacs et al., 2003; Al-Ghamdi et al., 2008;
The authors wish to thank Ms Gloria Ginzach for English language, grammar and syntax editing.
Yoel Shufaro MD, PhD, is the head of the Beilinson Infertility and IVF unit, and Senior Lecturer at the Felsenstein Medical Research Center, Faculty of Medicine, Tel-Aviv University. His clinical research focuses on optimizing ART and its feto–maternal outcome. His current basic research is focused on the field of fertility preservation and restoration. Key message In fresh embryo transfer cycles, a linear correlation exists between the entire range of pre-trigger endometrial
This difference was not present in the subgroup analyses. Furthermore, mean values in all studies lie within the earlier reported optimal range at trigger day (Simeonov et al., 2020); hence, no signs of a negative effect of letrozole were found on the endometrium. It has been proposed that, by suppressing oestradiol levels during ovarian stimulation, letrozole possibly has a beneficial effect on the endometrial receptivity, but data supporting this are lacking at present.
This was probably reflected by the fact that only 12% of fresh and 14% of frozen ETs were performed with an EMT of <8 mm in the Canadian in vitro fertilization registry data, whereas 27% of our ETs were performed with an EMT of <8 mm, when a minimum EMT was not required for ET. Simeonov et al. (11) retrospectively analyzed the relationship of the EMT on the trigger day and the LBR in 5,133 IVF cycles. In their analysis, they reported a significant and linear relationship between the 2 with LBRs of 34.2%, 25.6%, 23.4%, 18%, and 11.2% for EMTs of ≥16 mm, 13–15 mm, 10–12 mm, 7–9 mm, and <6 mm, respectively.
Yoel Shufaro MD, PhD, is the head of the Beilinson Infertility and IVF unit, and Senior Lecturer at the Felsenstein Medical Research Center, Faculty of Medicine, Tel-Aviv University. His clinical research focuses on optimizing ART and its feto–maternal outcome. His current basic research is focused on the field of fertility preservation and restoration. Key message In fresh embryo transfer cycles, a linear correlation exists between the entire range of pre-trigger endometrial thickness measurements and live birth rate. The thicker the endometrium, the higher the live birth rate, even after correction for age and ovarian response.
Contributed equally and should be considered joint first authors.