Article
Should we continue to measure endometrial thickness in modern-day medicine? The effect on live birth rates and birth weight

https://doi.org/10.1016/j.rbmo.2017.12.016Get rights and content

Abstract

The evaluation of endometrial thickness (EMT) is still part of standard cycle monitoring during IVF, despite the lack of robust evidence of any value of this measurement to predict little revalidation in contemporary medical practice; other tools, however, such as endocrine profile monitoring, have become increasingly popular. The aim of this study was to reassess whether EMT affects the outcome of a fresh embryo transfer in modern-day medicine, using a retrospective, single-centre cohort of 3350 IVF cycles (2827 women) carried out between 2010 and 2014. In the multivariate regression analysis, EMT was non-linearly associated with live birth, with live birth rates being the lowest with an EMT less than 7.0 mm (21.6%; P < 0.001) and then between 7.0 mm and 9.0 mm (30.2%; P = 0.008). An EMT less than 7.0 mm was also associated with a decrease in neonatal birthweight z-scores (−0.40; 95% CI −0.69 to −0.12). In conclusion, these results reaffirm the use of EMT as a potential prognostic tool for live birth rates and neonatal birthweight in contemporary IVF, namely when considered together with other ovarian stimulation monitoring methods, such as the late-follicular endocrine profile.

Introduction

Over the years, much has been published on potential sonographic markers for endometrial receptivity. Although it remains a controversial issue, endometrial thickness (EMT) is the most widely used prognostic factor for endometrial receptivity during assisted reproductive techniques (Kasius et al., 2014).

Several mechanisms are responsible for modifications caused to the morphology and histology of the endometrium before embryo implantation. Specifically, previous studies have shown that endometrial proliferation is dependent on reproductive age, hormonal levels of oestradiol and the expression of endometrial receptors (Paulson, 2011, Zhang et al, 2005).

Debate on the predictive value measuring EMT before administering HCG for ovulation triggering in assisted reproduction techniques is ongoing. Some investigators have shown a linear correlation between pregnancy rates and EMT (Al-Ghamdi et al, 2008, Chen et al, 2010, Richter et al, 2007, Rinaldi et al, 1996); however, others have posited that pregnancy rates may even decline above a thickness of 14 mm (Weissman et al., 1999), after which miscarriage rates may increase. Moreover, in a retrospective study (Lamanna et al., 2008) including 606 women undergoing a long-agonist protocol, the investigators reported a parabolic trend in pregnancy rate across EMT categories (with lower pregnancy rate in EMT extremes below 8 mm and above 14 mm, respectively). In 2014, a meta-analysis of 22 studies concluded that the measurement of EMT was a valuable predictor for clinical pregnancy, with lower clinical pregnancy rates below the frequently mentioned cut-off of 7 mm, which progressively increased until 10 mm of EMT (Kasius et al., 2014). On the basis of these results, one could conclude that a thick endometrium may not necessarily predict pregnancy but, conversely, a thin endometrium may be associated with lower pregnancy rates, possibly owing to a thinner functional layer that exposes the embryo to the higher oxygen concentrations of the blood from the spiral arteries during implantation (Casper, 2011).

Adequate endometrial development seems to be of paramount importance for placentation, given that previous studies have shown an association between abnormal glandular or vascular development and defective-placentation disorders, including placental abruption, low birth weight (LBW), fetal growth restriction, pregnancy-related hypertensive disorders and pregnancy loss (Palatnik et al, 2016, Pelinck et al, 2010a, Pelinck et al, 2010b; Rombauts et al, 2014, Toal et al, 2007). Most of the previously mentioned studies relate EMT to pregnancy rate with no mention of the potential effect on neonatal morbidity (Holden et al, 2017, Ma et al, 2017, Yuan et al, 2016), despite the common knowledge that assisted reproduction techniques are associated with preterm birth and LBW (Declercq et al, 2015, Jackson et al, 2004, Poikkeus et al, 2007, Schieve et al, 2002). The contributing factors of LBW after assisted reproduction techniques are immense, with little agreement on the main underlying causes. Multiple studies have pointed to either certain relevant baseline characteristics of the population seeking assisted reproduction techniques or specificities in the stimulation protocols and laboratory procedures (Bower, Hansen, 2005, Doyle et al, 1992, Helmerhorst et al, 2004, Jackson et al, 2004, Ludwig et al, 2006, Putterman et al, 2003, Schieve et al, 2002, Wang et al, 2005). Specifically, subfertility itself is a risk factor for LBW (Axmon, Hagmar, 2005, Basso, Baird, 2003, Bergh et al, 1999, Draper et al, 1999, Pandian et al, 2001), with conflicting results on whether specific causes of infertility pose a higher risk than others (Doyle et al, 1992, Wang et al, 2005). Some evidence also suggests a detrimental effect of the hyperestrogenic milieu on neonatal outcomes, given that neonates resulting from minimal-stimulation IVF may have higher birth weights compared with conventional IVF newborns (Pelinck et al, 2010a, Pelinck et al, 2010b). Furthermore, others have associated EMT less than 10 mm with an increased risk of adverse perinatal outcomes, including preterm delivery, LBW and fetal demise (Chung et al., 2006), an association which may be explained by a reduced selective capacity of thinner endometria (Oron et al., 2016).

Monitoring of both the endometrial and ovarian responses to ovarian stimulation with transvaginal ultrasound has become an important predictor of the success of assisted reproduction techniques (McWilliams and Frattarelli, 2007). Also, many agree that a concomitant hormonal assessment may also be beneficial in predicting assisted reproduction technique outcome (Hardiman et al, 1990, Loumaye et al, 1997, Rizk, Smitz, 1992), although it is not universally applied (Murad, 1998, Vandekerckhove et al, 2014) because supraphysiologic hormone levels during ovarian stimulation seem to be the underlying mechanism causing a so-called ‘endometrium-embryo asynchrony’ (Al-Azemi et al, 2012, Kyrou et al, 2009, Roque et al, 2013, Shapiro et al, 2011). More specifically, it has been reported that abnormal serum progesterone levels may be associated with lower ongoing pregnancy rate and live birth rates (Bosch et al, 2010, Kolibianakis et al, 2002, Santos-Ribeiro et al, 2014).

The main aim of this study was to estimate the predictive value of EMT in live birth and the neonatal outcomes of fresh embryo transfers in contemporary medicine, accounting specifically for the endocrine profile of the patient during the late-follicular phase.

Section snippets

Study design

This retrospective, single-centre, cohort study included assisted reproduction technique treatment cycles carried out at the Universitair Ziekenhuis, Brussels, between January 2010 and December 2014. Only cycles in which patients underwent a gonadotrophin-releasing hormone (GnRH) antagonist down-regulated stimulation protocol followed by a fresh embryo transfer were included. To minimize confounding derived from women with a baseline poor prognosis, we excluded cycles in women aged 40 years or

Patient baseline demographics and general characteristics of the treatment cycle

A total of 3350 cycles (carried out in 2827 women) were included in the analysis. The baseline demographics and main cycle characteristics according to EMT are presented in Table 1 and Table 2. The distribution of the following characteristics before oocyte retrieval varied significantly among the many EMT categories: BMI (P < 0.001), total dose of exogenous gonadotrophins (P = 0.003), duration of ovarian stimulation (P = 0.017) and late-follicular oestradiol (P = 0.001). Conversely, the number

Discussion

Despite significant advancements in the fields of ultrasonography (Singh et al, 2011, Wang et al, 2010, Zhang et al, 2016), immunology (Seshadri and Sunkara, 2014) and molecular diagnostics (Koot et al, 2016, Ruiz-Alonso et al, 2013), the potential benefit of these novel approaches are yet to be confirmed, leaving most physicians with only the measurement of EMT during ovarian stimulation to aid in the decision of whether or not to carry out a fresh embryo transfer. The main aim of the present

Samuel Santos-Ribeiro obtained his medical degree in 2007 from Nova Medical School (Lisbon), concluding his training in Obstetrics and Gynaecology at Hospital Santa Maria (Lisbon) in 2015. In 2013, he also initiated a research programme at Universitair Ziekenhuis Brussel (Brussels) with his PhD thesis focusing primarily on the optimization of endometrial receptivity.

Key message

This study reaffirms the usefulness of endometrial thickness as a potential prognostic tool for live

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    • Association between endometrial thickness and birth weight in fresh IVF/ICSI embryo transfers: a retrospective cohort study of 9273 singleton births

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      Citation Excerpt :

      Most previously published studies have focused on the analysis of pregnancy outcomes related to endometrial thickness (EMT), but only limited studies further explored the association between EMT and neonatal outcomes, and that their findings were inconsistent. Ribeiro et al. (2018), Zhang et al. (2019) and Guo et al. (2020) reported that a lower EMT was associated with an increased risk of small for gestational age (SGA) and a lower birth weight or birth weight z-score, but Oron et al. (2018) found no statistically significant association. In addition, most previously pubilshed studies treated EMT as a categorical variable, which impeded them from establishing a clear dose-response relationship between EMT and birth weight.

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    Samuel Santos-Ribeiro obtained his medical degree in 2007 from Nova Medical School (Lisbon), concluding his training in Obstetrics and Gynaecology at Hospital Santa Maria (Lisbon) in 2015. In 2013, he also initiated a research programme at Universitair Ziekenhuis Brussel (Brussels) with his PhD thesis focusing primarily on the optimization of endometrial receptivity.

    Key message

    This study reaffirms the usefulness of endometrial thickness as a potential prognostic tool for live birth rates and neonatal birthweight in contemporary IVF, particularly when considered together with other ovarian stimulation monitoring methods, such as the late-follicular endocrine profile.

    1

    The first two authors should be regarded as joint first authors.

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