Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome

Abstract

Study question: What is the independent contribution of endometrial thickness (EMT) on day of embryo transfer to achieving an ongoing pregnancy and live birth after IVF treatment?

Summary answer: EMT is a poor predictor of IVF success and has only little independent prognostic value.

What is known already: In a number of previous studies, pregnancy rates have been found to be lower in patients with thin endometrium.

Study design size duaration: This is a retrospective analysis of data from two large, randomized phase III studies (conducted in Europe and the USA) comparing s.c. progesterone with vaginal progesterone for luteal phase support. The studies were very similar in design, patient population and outcome, and the study data were combined and analysed on an individual patient level.

Participants/materials setting method: Subjects were infertile patients with an indication for IVF/ICSI, aged between 18 and 42 years, BMI <30 kg/m², <3 prior ART cycles and ≥ 3 oocytes after controlled ovarian stimulation with GnRH-agonist or GnRH-antagonist. EMT was assessed on day of embryo transfer (n = 1401). The association of EMT and ongoing pregnancy rate was determined by comparison of outcomes by quantiles of EMT. The predictive capacity of EMT for ongoing pregnancy achievement was assessed at each millimeter cut-off. Finally, a regression model was built to determine the contribution of EMT among other confounders, such as age and oocyte numbers, on the likelihood of ongoing pregnancy and live birth.

Main results and the role of chance: In univariate analysis, ongoing pregnancy rates correlate to EMT. In patients above a cut-off of ≥9 mm EMT, the chance of pregnancy was higher as compared to patients with an EMT of 3-8 mm (odds ratio (OR) = 1.69, 95% CI: 1.23-2.35, P = 0.001; sensitivity 88.89%, specificity 17.52%, positive predictive value 39.02%, negative predictive value 72.64% and likelihood ratio 1.08). In multivariate regression analysis, after controlling for trial, female age and oocyte numbers, EMT was a statistically significant predictor of live birth (OR = 1.05, 95% CI: 1.00-1.10; P = 0.0351). If EMT indeed is an independent factor affecting outcome, this finding implies that at a baseline live birth rate of 20% an increase of 2 mm in EMT should result in an increase of the live birth rate of ~1.6%.

Limitations reasons for caution: The independent contribution of EMT to live birth likelihood is small and may result from (undetermined) confounding. The EMT on day of embryo transfer is usually higher as compared to the EMT on day of triggering final oocyte maturation when it is conventionally assessed during routine cycle monitoring. Furthermore, endometrial lining pattern and/or subendometrial Doppler flow have not been assessed and, accordingly, the conclusions of this work are limited to only the thickness of the endometrium.

Wider implications of the findings: EMT can be ignored during cycle monitoring of the majority of IVF patients and only the extremes of EMT deserve further diagnostic work-up.

Study funding/competing interests: The study was supported by IBSA. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. S.T. and B.C. are employees of IBSA.

Trial registration number: NCT00827983 and NCT00828191 (clinicaltrials.gov).

Trial registration date: 23 January 2009 (NCT00827983 and NCT00828191).

Date of first patient’s enrolment: January 2009 (NCT00827983 and NCT00828191).

Keywords: IVF; IVF outcome; endometrial thickness; endometrium; pregnancy rates; thin endometrium.

Figure 1

Distribution of patients by endometrial thickness on the day of embryo transfer. Mean (±SD) and median endometrial thickness were 11.08 (±2.40) and 10.90, respectively.

Figure 2

Ongoing pregnancy rates by percentiles of endometrial thickness. The error bars show the 95% CIs.

Figure 3

Odds ratios with 95% CIs for ongoing pregnancy achievement for different cut-offs of endometrial thickness. OR = odds ratio; EMT = endometrial thickness.