Abstract
Aim : Our aim was to investigate the role of endometrial thickness and pattern in the pregnancy rate during an in vitro fertilization‐embryo transfer (IVF‐ET) cycle.
Methods : Records of patients who underwent IVF‐ET at the Jichi Medical School Hospital during May 1995–December 1999 were evaluated retrospectively. Only cycles, in which endometrial thickness and pattern on the day of human chorionic gonadotrophin (HCG) administration were recorded, were analyzed in this study. Endometrial thickness was divided into three categories (A: < 10 mm, B: 10–14 mm, C: > 14 mm), and endometrial pattern was divided into two categories: triple line and non‐triple line. A total of 156 IVF‐ET cycles from 120 patients was evaluated.
Results : There were no significant differences for both the endometrial thickness and pattern in the pregnancy rate during the IVF‐ET cycle (P > 0.05). Among the study groups, the triple‐line endometrial pattern was found to be 58.7% in group A, 84.0% in group B and 70% in group C. We found that in the triple‐line endometrial pattern, there was a significant difference between group A and group B (P < 0.01). Triple‐line endometrial pattern appeared significantly in younger women (33 ± 5.4 years) than in non‐triple‐line endometrial pattern (36 ± 5.2 years; P = 0.047). The minimum and maximum endometrial thickness where pregnancy occurred was 6.5 mm (two pregnancies) and 19 mm (one pregnancy), respectively.
Conclusion : Endometrial thickness and pattern have no influence on the pregnancy rates in an IVF‐ET cycle, but patients with triple‐line endometrial pattern and group B endometrial thickness showed a better pregnancy outcome in the IVF‐ET treatment. (Reprod Med Biol 2002; 1: 17–21)
Keywords: endometrial pattern, endometrial thickness, in vitro fertilization, pregnancy rate
Introduction
ASSESSMENT OF THE endometrium with ultrasound has become a standard procedure during the diagnostic work‐up and treatment of infertility. Despite the widespread use of high‐resolution ultrasound equipment, the clinical significance of differences in endometrial thickness and pattern has remained controversial. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9
Endometrial thickness in the periovulatory period, as measured by transvaginal ultrasonography, has been correlated with clinical pregnancy rates in in vitro fertilization‐embryo transfer (IVF‐ET) cycles. 1 , 2 , 4 , 8 Thus, previous studies have indicated that retardation in the endometrial development has been linked to low conception rates as well as increased spontaneous abortion rates. 8 In contrast, increased endometrial thickness has recently been reported to have a detrimental effect on implantation rates, pregnancy rates and outcome in IVF‐ET. 2 In addition, abnormalities in the normal triple‐line endometrial pattern have been found in association with low pregnancy rates. Lower implantation rates and pregnancy rates in women who exhibit a homogenous pattern have been reported, although there have also been conflicting results. 1 , 4
In this study, our objective was to investigate whether endometrial thickness and pattern are associated with the pregnancy rates in IVF‐ET.
Materials and methods
THE RECORD OF patients who underwent IVF‐ET at the Jichi Medical School Hospital during May 1995–December 1999 was evaluated retrospectively. Only cycles in which endometrial thickness and endometrial pattern on the day of human chorionic gonadotrophin (HCG) administration were recorded, were analyzed.
All cycles included a stimulation of ovarian function and an induction of ovulation with gonadotrophins according to long and short protocols with gonadotrophin, a releasing hormone (GnRH) agonist. The assessments of endometrial thickness and pattern were performed by using transvaginal ultrasonography. Endometrial thickness was divided into three categories: A, endometrial thickness < 10 mm; B, endometrial thickness 10–14 mm; and C, endometrial thickness > 14 mm. The endometrial pattern was divided into two categories: triple line and non‐triple line.
The endometrial pattern was measured transvaginally in the central longitudinal axis from the echogenic interphase of the endometrium junction. The triple‐line pattern was defined by the appearances of triple hyperechoic lines (Fig. 1a); therefore, a non‐triple‐line pattern showed no triple hyperechoic lines (Fig. 1b) in the center of the uterine body. Endometrial thickness was measured at the site of maximum thickness from both sides of the midline.
Figure 1.
Transvaginal ultrasound image of the endometrial pattern. Triple‐line pattern was defined by the appearances of triple hyperechoic lines as illustrated in the plane through the central longitudinal axis of the uterine body (a), non‐triple‐line pattern showed no triple hyperechoic lines (b). The endometrial thickness was measured at the site of maximum thickness from both sides of the midline.
Pregnancy was considered as a case that showed a definite gestational sac, as indicated by the use of an ultrasound examination. Statistical analysis of the data was performed by using χ2 analysis and Student’s t‐test analysis using statview 4.5 (Abacus Concepts, Berkeley, CA, USA) for Macintosh, and P < 0.05 was considered to be significant.
Results
PATIENTS WITHOUT RECORDS of endometrial thickness and pattern at the HCG administration were excluded from the present study. A total of 156 IVF‐ET cycles from 120 patients was evaluated.
Patient characteristics in the pregnancy and non‐pregnancy group
There were no differences in the age of patients, duration of infertility, number of follicles, number of oocyte retrievals, and number of mature oocyte both in the pregnancy and the non‐pregnancy groups. The number of embryos transferred was significantly higher in the pregnancy group (P < 0.01; Table 1).
Table 1.
Characteristics of the study subject in the pregnancy and non‐pregnancy groups
| Pregnancy | Non‐pregnancy | P | |
|---|---|---|---|
| Age (years) | 33.4 ± 4.4 | 34.4 ± 5.8 | NS |
| No. cycles treated | 1.5 ± 0.8 | 1.4 ± 0.7 | NS |
| Duration of infertility (months) | 51.2 ± 41.1 | 61.3 ± 45.3 | NS |
| No. embryos transferred | 3.5 ± 1.5 | 2.8 ± 1.4 | < 0.01 |
| No. oocytes retrieved | 10.1 ± 5.2 | 8.4 ± 6.3 | NS |
| No. mature oocytes obtained | 6.9 ± 4.1 | 6.1 ± 4.9 | NS |
NS, not significant.
Pregnancy rates in correlation with the endometrial thickness and pattern
The pregnancy rate was 39/156 (25.0%) in all cycles, and in patients with a triple‐line endometrial pattern, the percentage of pregnancy rates was 18.5, 29.8 and 28.6% in groups A, B and C endometrial thickness, respectively. The pregnancy rate in patients with a non‐triple‐line endometrial pattern was 15.8, 25.0, and 0% in endothelial thickness groups A, B and C, respectively. There were no significant differences (P > 0.05) found in any of the groups (Table 2).
Table 2.
Pregnancy rates in correlation with endometrial thickness and pattern*
| Endometrial thickness | Endometrial pattern | ||
|---|---|---|---|
| Tripe line (%) | Non‐triple line (%) | Total (%) | |
| Group A (< 10 mm) | 5/27 (18.5) | 3/19 (15.8) | 8/46 (17.4) |
| Group B (10–14 mm) | 25/84 (29.8) | 4/16 (25.0) | 29/100 (29.0) |
| Group C (> 14 mm) | 2/7 (28.6) | 0/3 (0) | 2/10 (20.0) |
| Total (%) | 32/118 (27.1) | 7/38 (18.4) | 39/156 (25.0) |
There were no significant differences.
Treatment cycle distribution in the endometrial thickness and pattern
The triple‐line endometrial patterns were 58.7, 84.0 and 70.0% in groups A, B and C, respectively. A significant difference was found between groups A and B in the triple‐line endometrial pattern (P < 0.001; Table 3).
Table 3.
Treatment cycle distribution in the endometrial thickness and pattern
| Endometrial thickness | Endometrial pattern | |
|---|---|---|
| Triple line (%) | Non‐triple line (%) | |
| Group A (< 10 mm) | 27 (58.7)* | 19 (41.3) |
| Group B (10–14 mm) | 84 (84)* | 16 (16) |
| Group C (> 14 mm) | 7 (70) | 3 (30) |
P < 0.001.
Age distributions in endometrial thickness and pattern
In the triple‐line endometrial pattern, the age distributions were 32.4 ± 5.9, 34.5 ± 5.3 and 31.9 ± 4.5 years in endometrial thickness groups A, B and C, respectively. In the non‐triple‐line endometrial pattern, the age distributions were 37.8 ± 5.1, 33.0 ± 4.6 and 36.7 ± 4.0 years in groups A, B and C, respectively. A significant difference was found in the triple‐line pattern (33.4 ± 5.4 years) as compared with the non‐triple line pattern (36.7 ± 5.2 years; P < 0.05; Table 4).
Table 4.
Age distributions in endometrial thickness and pattern
| Endometrial thickness | Endometrial pattern | ||
|---|---|---|---|
| Triple line | Non‐triple line | Total | |
| Group A (< 10 mm) | 32.4 ± 5.9 | 37.8 ± 5.1 | 34.6 ± 6.2 |
| Group B (10–14 mm) | 34.5 ± 5.3 | 33.0 ± 4.6 | 34.2 ± 5.2 |
| Group C (> 14 mm) | 31.9 ± 4.5 | 36.7 ± 4.0 | 32.9 ± 4.9 |
| Total | 33.4 ± 5.4* | 36.7 ± 5.2* | – |
Results are presented as mean ± SD. *P < 0.05.
Two abortions occurred in patients aged > 39 years old. One of them showed an endometrial thickness of 8 mm and a non‐triple‐line endometrial pattern, and the other showed an endometrial thickness of 10 mm and a triple‐line endometrial pattern. The minimum value of endometrial thickness where pregnancy was established was 6.5 mm (in two pregnancies). No pregnancy occurred in the patient aged > 42 years.
Discussion
THE ULTRASONOGRAPHIC ASSESSMENT of uterine receptivity is a favorable choice because of its simplicity and because it is less traumatic on the reproductive tract. Endometrial thickness had been correlated with the pregnancy rate during an IVF‐ET treatment cycle. Pregnancy not only rarely occurred with thin endometrial thickness, but the chances of pregnancy also decreased with increased endometrial thickness. 2 , 4 , 7 , 10 , 11 Recently, a study on the endometrial echogenicity showed a poor IVF‐ET outcome in the hyperechogenic transformation of the endometrium. 12 However, our study showed that endometrial thickness was not correlated with pregnancy rates during IVF‐ET treatment. Endometrial thickness had been reported to have no accuracy predicting the outcome of an IVF‐ET treatment cycle. 1 , 8 , 13 , 14 Schild et al., in their 3‐D ultrasonographic study, also mentioned that a 3‐D volume estimation of endometrium, as well as an analysis of the endometrial thickness, had no predictive value on the pregnancy rate during an IVF‐ET treatment cycle. 15
In comparison with other groups, the triple‐line pattern appeared in the highest percentage when endometrial thickness was 10–14 mm (group B endometrial thickness). Our study supports the previous report by Yamashita et al., 10 in which thicker endometrial thickness and triple‐line endometrial pattern were found in the pregnant cycles. However, whether both variables had a correlation was not clearly explained.
The present study showed that the endometrial pattern was significantly influenced by age (Table 4). Triple‐line endometrial pattern was likely to appear in younger patients compared with the non‐triple‐line endometrial pattern. Similarly, Lass et al. reported in their histopathological study that a younger age was correlated with advanced staging in the endometrium. 16 Sauer et al. also investigated the effect of aging on the endometrial pattern, although they found that there was no age relation in the ultrasonographic appearance. 17
No pregnancies occurred when endometrial thickness was less than 6.5 mm. A similar study was reported by Carolyn et al., who also mentioned that no pregnancy occurred when the endometrial thickness was less than 6 mm. 6
The role of uterine receptivity is likely to be more important in cases where excellent embryos are replaced. 5 , 18 , 19 The probability of implantation is increased obviously in the presence of at least one good embryo. 5 Our present study showed that the pregnancy rate was greater with the increased number of embryos transferred. Terriou et al. also reported similar findings. 19 However, the transfer of more than four embryos in one treatment cycle was also related to decreasing the pregnancy rate, as a transfer of more than four embryos was usually performed in cases with multiple implantation failures. 19 Recently, Dean et al. 20 reported that in patients < 35 years of age who have three or more good‐quality embryos, a transfer of a maximal two good embryos has no difference in comparison with a transfer of more embryos in achieving high pregnancy rates; this resulted in a 10‐fold decrease of the multiple pregnancies.
The present study has some limitations that may influence our results. First, the number of cases was fewer, especially in patients with an endometrial thickness > 14 mm. Therefore, we could not make a reliable analysis of the group with thick endometrial thickness (group C). Increased endometrial thickness has been reported to reduce the pregnancy rate significantly, and cause a high risk of spontaneous abortions. 2 , 21 Second, we were unable to explain the influence of estradiol and progesterone in the endometrial structure because of a lack of data in our records. Estradiol has been reported to have an important role in endometrial thickness. 3 , 22 Barash et al. reported that a thin endometrial thickness was significantly related to a lower estradiol concentration. 22 Moreover, an ovarian stimulation protocol has also been reported to be able to support the growth of endometrium in order to achieve desired thickness. 22 , 23
In conclusion, endometrial thickness and pattern alone were not sufficient variables to predict the pregnancy rate during IVF‐ET treatment cycles. However, patients with a triple‐line endometrial pattern and an endometrial thickness of 10–14 mm showed a better pregnancy outcome when they received an IVF‐ET treatment cycle. Further advanced studies are needed to provide an answer to this contradictory opinion about the roles of endometrial thickness and endometrial pattern during IVF‐ET treatment cycles.
References
- 1. Sharara FI, Lim J, McClamrock HD. Endometrial pattern on the day of oocyte retrieval is more predictive of implantation success than the pattern or thickness on the day of HCG administration. J Assist Reprod Genet 1999; 1: 523–528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Weissman A, Gotlieb L, Casper RF. The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in an in vitro fertilization program. Fertil Steril 1999; 72: 147–149. [DOI] [PubMed] [Google Scholar]
- 3. Christian G, Matthias S, Maria G, Eberhard N, Wolfgang H, Schneider HPG. Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1186 infertile women. Fertil Steril 2000; 73: 106–113. [DOI] [PubMed] [Google Scholar]
- 4. Vera JA, Arguello B, Cristosto CA. Predictive value of endometrial pattern and thickness in the result of in vitro fertilization and embryo transfer. Rev Chil Obstet Ginecol 1995; 60: 195–198. [PubMed] [Google Scholar]
- 5. Commenges D, Tricaud A, Papaxanthos R, Dallay D, Horovitz J. Modelling of the probability of success of the stages of in‐vitro fertilization and embryo transfer: stimulation, fertilization and implantation. Hum Reprod 1998; 13: 78–83. [DOI] [PubMed] [Google Scholar]
- 6. Carolyn BC, Bustillo M, Soenksen DM, Britten S. Ultrasonographic predictors of implantation after assisted reproduction. Fertil Steril 1994; 62: 1004–1010. [DOI] [PubMed] [Google Scholar]
- 7. Gonen Y, Robert FC, Jacobson W, Blankier J. Endometrial thickness and growth during ovarian stimulation: a possible predictor of implantation in in vitro fertilization. Fertil Steril 1989; 52: 446–450. [DOI] [PubMed] [Google Scholar]
- 8. Csemiczky G, Wramsby H, Johannisson E, Landgren BM. Endometrial evaluation is not predictive for in vitro fertilization treatment. J Assist Reprod Genet 1999; 16: 113–116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Yang JH, Wu MY, Chen CD, Jiang MC, Ho HN, Yang YS. Association of endometrial blood flow as determined by a modified color Doppler technique with subsequent outcome of in‐vitro fertilization. Hum Reprod 1999; 14: 1606–1610. [DOI] [PubMed] [Google Scholar]
- 10. Yamashita M, Park K, Shiotani M et al. Relation between transvaginal ultrasonographic appearance of endometrium and pregnancy rates during in vitro fertilization. IX World Congress in-Vitro-Fertilization Alternated Assisted Reprod 1995; 3–7: 399–404. [Google Scholar]
- 11. Kwon HC, Ryn HS, Yang JI, Chang KH, Oh KS. The effectiveness of endometrial thickness for prediction of implantation in IVF‐ET. IX World Congress in-Vitro-Fertilization Alternated Assisted Reprod 1995; 3–7: 411–417. [Google Scholar]
- 12. Fanchin R, Righini C, Ayoubi JM, Olivennes F, Ziegler D, Frydman R. New look at endometrial echogenicity: objective computer‐assisted measurements predict endometrial receptivity in in vitro fertilization‐embryo transfer. Fertil Steril 2000; 74: 274–281. [DOI] [PubMed] [Google Scholar]
- 13. Salle B, Damon BV, Benchaib M, Desperes S, Gaucherand P, Rudigoz RC. Preliminary report of an ultrasonography and colour Doppler uterine score to predict uterine receptivity in an in‐vitro fertilization programme. Hum Reprod 1998; 13: 1663–1673. [DOI] [PubMed] [Google Scholar]
- 14. Lesny P, Killick SR, Tetlow RL, Manton DJ, Robinson J, Maguiness SD. Ultrasound evaluation of the uterine zonal anatomy during in‐vitro fertilization and embryo transfer. Hum Reprod 1999; 14: 1593–1598. [DOI] [PubMed] [Google Scholar]
- 15. Schild RL, Indefrei D, Eschweiler S, Van der Ven H, Fimmers R, Hansmann M. Three‐dimensional endometrial volume calculation and pregnancy rate in an in‐vitro fertilization programme. Hum Reprod 1999; 14: 1255–1258. [DOI] [PubMed] [Google Scholar]
- 16. Lass A, Peat D, Avery S, Brinsden P. Histological evaluation of endometrium on the day of oocyte retrieval after gonadotrophin‐releasing hormone agonist‐follicle stimulating hormone ovulation induction for in‐vitro fertilization. Hum Reprod 1998; 13: 3203–3205. [DOI] [PubMed] [Google Scholar]
- 17. Sauer MV, Miles RA, Dahmoush L, Paulson RJ, Press M, Moyer D. Evaluating the effect of age on endometrial responsiveness to hormone replacement therapy: a histologic ultrasonographic, and tissue receptor analysis. J Assist Reprod Genet 1993; 10: 47–52. [DOI] [PubMed] [Google Scholar]
- 18. Tan SL, Biljan MM. Clinical assessment of uterine receptivity In: Shoham Z, Howles CM, Jacobs HS. (eds), Female Infertility Therapy. London: Martin Dunitz Ltd, 1999;. 407–417. [Google Scholar]
- 19. Terriou P, Sapin C, Giorgetti C, Hans E, Spach JL, Roulier R. Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age. Fertil Steril 2001; 75: 525–531. [DOI] [PubMed] [Google Scholar]
- 20. Dean NL, Phillips SJ, Buckett WM, Biljan MM, Tan SL. Impact of reducing the number of embryos transferred from three to two in women under the age of 35 who produced three or more high‐quality embryos. Fertil Steril 2000; 74: 820–823. [DOI] [PubMed] [Google Scholar]
- 21. Chiang CH, Chang MY, Shiau CS, Hou HC, Hsieh TT, Soong YK. Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization‐embryo transfer. J Assist Reprod Genet 1999; 16: 369–372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Barash A, Weissman W, Manor M, Milman D, Ben‐Arie A, Shoham Z. Prospective evaluation of endometrial thickness as a predictor of pituitary down‐regulation after gonadotrophin‐releasing hormone analogue administration in an in vitro fertilization program. Fertil Steril 1998; 69: 496–499. [DOI] [PubMed] [Google Scholar]
- 23. Cacciatore B, Simberg N, Tiitinen A, Ylikorkala O. Evidence of interplay between plasma endothelin‐1 and 17 β‐estradiol in regulation of uterine blood flow and endometrial growth in infertile women. Fertil Steril 1997; 67: 883–888. [DOI] [PubMed] [Google Scholar]