Relationship between thickness and pattern of endometrium and pregnancy rate in in vitro fertilization-intracytoplasmic sperm injection cycles

© 2018 The Authors; Tabriz University of Medical Sciences This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Relationship between thickness and pattern of endometrium and pregnancy rate in in vitro fertilization-intracytoplasmic sperm injection cycles

Assisted reproductive treatments (ART) have been used for treatment of infertility.Despite technical advances, the implantation rate is still low.High procedure expenses with low implantation and pregnancy rate in in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) has emerged the need to identify the factors predicting the procedure success. 1,2mbryo quality and endometrial receptivity are two important factors of ART cycle success.Identifying the factors affecting the endometrial receptivity could improve the outcome. 3With proper hormonal and structural basis, endometrium will grow to appropriate thickness and would be suitable for embryo implantation. 4][7][8][9][10][11][12] Some studies have shown that suitable thickness for implantation is between 7-14 mm and the likelihood of pregnancy is decreased in values below and above this rate.][15][16] There is no definite endometrial thickness in which IVF-ICSI cycle would increase the pregnancy rate.In this study, we evaluated the correlation between endometrial pattern and thickness with pregnancy rate in IVF-ICSI cycles.All participants were treated with GnRH antagonist protocol.Patients received recombinant human follicle stimulating hormone Follitropin Alfa (Gonal-F) (150-225 IU, subcutaneously) and human menopausal gonadotropin (hMG) 75-150 IU from day 2-3 of menstruation.Serial trans-vaginal sonography was performed.When the mature follicle (≥ 13.0 mm) was detected, GnRH antagonist (Cetrotide) (0.25 mg/day, subcutaneously) was injected.Triggering was started with 10000 IU human chorionic gonadotropin (HCG) (Pregnyl, Organon, Netherland) when at least three follicles with a mean diameter of 18.0 mm was observed.36 hours after HCG injection, oocytes were punctured and embryo transfer was performed three days later.The pregnancy test (serum βHCG) was performed two weeks after embryo transfer.
Endometrial thickness was defined as the maximal distance between the echogenic interfaces of the myometrium and the endometrium and was measured in the midsagittal plane by two dimensional transvaginal ultrasound on the day of HCG administration.Endometrial pattern was classified as pattern A, pattern B, or pattern C as a triple-line pattern consisting of a central hyperechoic line surrounded by two hypoechoic layers, an intermediate isoechogenic pattern with the same reflectivity as the surrounding myometrium and a poorly defined central echogenic line, as homogenous, hyperechogenic endometrium, respectively.
All data were analyzed using SPSS (version 17, SPSS Inc., Chicago, IL, USA).Results are expressed as mean ± standard deviation (SD) or percentage.The chi-square and Fisher exact tests were used to compare categorical variables.Receiver operating curve (ROC) and area under curve (AUC) were used to define cut-off point and for endometrial thickness in predicting pregnancy rate, respectively.Sensitivity and specificity of endometrial thickness alone and in line with endometrial pattern was calculated.The P values of less than 0.050 were considered statistically significant.
A total of 150 women with 150 IVF-ICSI cycles were studied.The mean age of patients and the mean duration of infertility was 31.70 ± 6.58 and 6.12 ± 4.72 years, respectively.126 (84.0%) and 24 (16.0%) of subjects suffered from the primary and secondary infertility, respectively.Causes of infertility were combined, male factor, tubal factors, and unexplained with rates of 51.3%, 29.3%, 17.3%, and 2.0%, respectively.Mean endometrial thickness was 9.14 ± 1.60 (ranging 6-14 mm).Endometrial pattern was type A and type B among 106 (70.7%) and 44 (29.3%) of patients, respectively.40 (26.7%) of patients had positive pregnancy tests.Positive pregnancy test was significantly higher in type A endometrial pattern than type B with 33.0% and 11.3%, respectively (P = 0.006).In addition, cases with positive pregnancy test had significantly higher endometrial thickness compared to the negative ones with 10.75 ± 1.67 and 8.56 ± 1.11, respectively (P < 0.001).All pregnancy cases occurred in thicknesses between 9.0-14.0mm.
Figure 1 shows the ROC with the AUC of 0.876 (P < 0.001) which yields to a cut-off value of 9.5 mm.Dividing the patients into groups with endometrial thickness < 9.5 and ≥ 9.5, pregnancy rate was significantly higher in the second group as 53.4% and 9.8%, respectively (P < 0.001).With a cut-off of 9.5 mm, the sensitivity and specificity of endometrial thickness in predicting positive pregnancy was 77.5% and 75.5%, respectively.Sensitivity, specificity, positive and negative predictive values of different endometrial thickness and endometrial pattern were evaluated alone or in combination with the endometrial thickness (Table 1).The highest sensitivity was obtained for endometrial thickness > 7.0 mm, however with the lowest specificity.The highest specificity were noted for endometrial thickness > 9.5 mm alone or in line with type A endometrial pattern.
Achieving a proper endometrial thickness is important for successful infertility treatment.Proper endometrial thickness and pattern affects implantation rate and consequently increases the clinical pregnancy rate. 17,18n this study, the correlation between endometrial thickness and pattern with pregnancy rate was evaluated in IVF-ICSI cycles.The pregnancy rate was 26.7%, in addition, the most successful pregnancies had high endometrial thickness and type A (triple line) sonographic endometrial pattern.
There are conflicting results regarding the correlation between endometrial thickness and pregnancy rate and proper thickness for highest pregnancy rate has not been yet found.Weissman et al. 19 reported that the pregnancy rate was decreased in cases with endometrial thickness > 14 mm which also increases the abortion risk.Rashidi et al. 20 found no significant difference in endometrial thickness between pregnant and non-pregnant women.They indicated that pregnancy occurred mostly in endometrial thickness between 9-12 mm. 20In the present study, all pregnancies occurred in endometrial thickness of 9-14 mm.Unlike Rashidi et al. 20 , the study by Momeni et al. 2 in their metaanalysis reported that endometrial thickness was higher among the pregnant women.In recent studies, endometrial pattern was also considered as an indicator of implantation; however, there was no consensus on the proper endometrial pattern to achieve successful pregnancy. 21The classification of endometrial pattern varies in different studies.Similar to findings of the present study, Ma et al. 9 noted that thick endometrium and triple line endometrial pattern have significant role in pregnancy rate.Kuc et al. 22 also mentioned that triple line pattern (TLP) had significant effect on pregnancy only among the patients receiving long agonist therapy protocol.Other studies found no significant difference between different endometrial pattern and pregnancy rate. 20,23,24lthough previous studies have shown that thin endometrium accompanies with poor pregnancy outcomes, 12,[25][26][27] there is no accepted cut-off for endometrial thickness which could properly determine pregnancy incidence.Moreover, there are reports of pregnancy in endometrial thickness of < 6 mm and even below 4.0 mm. 16Noyes et al. 28 observed that clinical pregnancy rate in endometrial thickness < 8.0 mm was lower than cases with endometrial thickness ≥ 9 mm.Furthermore, Al-Ghamdi et al. 4 indicated that endometrial thickness > 11 mm was acceptable for better pregnancy outcome.Kehila et al. 29 also noted that endometrial thickness > 12 mm increases the chance of successful pregnancy.
In the present study, the endometrial thickness > 9.5 mm resulted in significantly higher rate of pregnancy even higher than when considering a thickness of > 7 mm.In addition, it was observed that the combination of endometrial thickness (> 9.5 mm) and pattern (triple line) led to even higher rate of pregnancy.Chen et al. 23 reported that combination of both endometrial thickness and pattern compared to each one separately could be a better predictor of outcome of patients in IVF-ICSI cycles.
Thickness and pattern of endometrium both could predict pregnancy incidence.Having TLP along with endometrium thickness > 9.5 mm, the possibility of pregnancy following IVF-ICSI increases.We recommend to measure endometrial thickness and pattern among all patients receiving IVF-ICSI cycles to define the possibility rate of successful pregnancy.Moreover, if evaluations showed hypoecho pattern along with endometrial thickness < 7 mm, it is better to have cryopreservation for further cycles.

Figure 1 .
Figure 1.Receiver operating characteristic (ROC) curve for the predictive value of endometrial thickness for positive pregnancy test

Table 1 .
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of different endometrial thicknesses and endometrial pattern alone or in combination with the endometrial thickness