- Open Access
The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET) outcome
© Al-Ghamdi et al; licensee BioMed Central Ltd. 2008
- Received: 22 May 2008
- Accepted: 02 September 2008
- Published: 02 September 2008
To evaluate the relationship between endometrial thickness on day of human chorionic gonadotrophin administration (hCG) and pregnancy outcome in a large number of consecutive in vitro fertilization and embryo transfer (IVF-ET) cycles.
A retrospective cohort study including all patients who had IVF-ET from January 2003–December 2005 conducted at a tertiary center.
A total of 2464 cycles were analysed. Pregnancy rate (PR) was 35.8%. PR increased linearly (r = 0.864) from 29.4% among patients with a lining of less than or equal to 6 mm, to 44.4% among patients with a lining of greater than or equal to 17 mm. ROC showed that endometrial thickness is not a good predictor of PR, so a definite cut-off value could not be established (AUC = 0.55).
There is a positive linear relationship between the endometrial thickness measured on the day of hCG injection and PR, and is independent of other variables. Hence aiming for a thicker endometrium should be considered.
- Pregnancy Rate
- Embryo Transfer
- Assist Reproductive Technology
- Endometrial Thickness
- Endometrial Receptivity
Assisted reproductive technology (ART) has been commonly used in infertility treatment over the last two decades. The high cost and relatively low implantation and pregnancy rates (PRs) in in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment cycles has led to a need to evaluate the predictors of success in these patients. One of the important factors is the endometrial receptivity. Endometrial thickness has been utilized as an indirect indicator for endometrial receptivity and is measured in the midsaggital plane during transvaginal ultrasound, which is considered as both atraumatic and simple . The effect of endometrial thickness on pregnancy rates in ART patients has been evaluated by many authors [2–11], with controversial results. Some authors demonstrated a higher pregnancy rate at certain endometrial thickness [3, 4, 10–12], while others did not show a significant correlation between endometrial thickness and PRs in IVF/ICSI patients [5, 7, 8]. Other authors reported a threshold of <7 mm and/or >14 mm with a significant reduction in implantation rate and PR [2, 6].
With these controversies, no conclusive cut-off value of endometrial thickness has been established in order to help clinicians in counseling the couple about the outcome. The reason for such controversy could be probably due to a relatively low number of cycles for patients with both extremes of endometrial thicknessess.
The aim of this study is to determine if there is any effect of endometrial thickness measured on the day of administration of human Chorionic Gonadotrphin (hCG) on pregnancy rate while analyzing large number of cycles, and if so, to identify a cut off value at which pregnancy rate is too low, hence helping clinicians in counceling the couples.
All fresh cycles of IVF or ICSI conducted at King Faisal Specialist Hospital and Research Center IVF unit from January 2003 to December 2005 were identified from our electronic database and the charts were reviewed. The study was approved by the Ethics Committee of our hospital. All fresh IVF or ICSI treatment cycles that reached oocyte pick up and embryo transfer within the study period were included, women with known intrauterine anomalies were excluded from the study. Endometrial thickness was not used as a criteria for cancellation. 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.
Two protocols for pituitary down regulation were used, long or short protocol as previously described . The medication for stimulation used in all cases was human menopausal gonadotrophin (hMG, Menegon®, Ferring, Germany). When at least three follicles were ≥ 18 mm, hCG 10,000 units was administered. The endometrial thickness was measured by the same sonographer and documented in the chart. Oocyte retrieval was performed 36 hours later. Fertilization was achieved by IVF or ICSI according to the indication. Cleavage stage embryos were transferred on day 3. Maximum two embryos were transferred under transabdominal ultrasound guidance with a full bladder. The patients were started on IM progesterone injections (Gestone, Nordic Pharma, UK) on the same day of embryo transfer for luteal phase support and continued till pregnancy test on day 15. Clinical pregnancy was confirmed by ultrasound observation of fetal cardiac activity two weeks after positive hCG test.
The patients were divided into two groups; those who got pregnant (group A) and those who did not (group B). Both groups were compared for the various parameters including age, body mass index (BMI), diagnosis, number of oocyte retrieved, length of stimulation, dose of hMG, fertilization rate, number of cleaved embryos, number of transferred embryos.
Data were analyzed using SPSS version 14 software (Chicago, Ilin, USA). All tests were two tailed, and p < 0.05 was considered statistically significant. Continuous variables are presented as mean and SD and were tested by student's t-test. Comparisons of proportions were made by the chi-squared test. The effect of endometrial thickness on the pregnancy outcome was studied using multivariate analysis, where all other factors affecting the pregnancy outcome were controlled for. To determine the correlation between endometrial thickness, patient characteristics and treatment characteristics a stepwise logistic regression analysis was performed including (age of the patient, body mass index (BMI), endometrial thickness on day 3 of the cycle, duration of stimulation, dose of hMG needed, number of oocytes retrieved, number of cleaved embryos, and number of embryos transferred). The Receiver operating characteristic (ROC) analysis was used to evaluate an endometrial thickness that can predict pregnancy outcome.
mean ± SD
mean ± SD
Number of cycles (n)
30.27 ± 5.53
31.14 ± 5.38
BMI (weight kg/height m2)
28.44 ± 4.58
28.32 ± 4.42
Long protocol # (%)
Short protocol # (%)
Stimulation length (days)
10.92 ± 2.63
10.79 ± 2.46
Dose of hMG (ampoules)
37.67 ± 15.03
40.73 ± 16.54
Endometrial thickness cycle day 3 (mm)
3.23 ± 1.22
3.21 ± 1.22
Endometrial thickness hCG day (mm)
11.64 ± 2.13
11.26 ± 2.17
Number of medium sized follicles
8.08 ± 5.33
7.12 ± 5.31
Number of mature follicles
7.92 ± 3.51
7.62 ± 3.69
Number of oocytes retrieved
10.51 ± 5.43
9.86 ± 5.73
Number of fertilized oocytes
5.79 ± 3.23
4.97 ± 3.35
Number of embryos
5.3 ± 2.82
4.44 ± 2.81
Number of embryos transferred
1.88 ± 0.37
1.98 ± 0.26
Male factor 1763 (71.6%)
Tubal factor 338 (13.7%)
Unexplained 213 (8.6%)
Others 150 (6.1%)
Pregnancy rates at different endometrial thicknesses
Endometrial thickness on day of HCG
Group A (n)
Group B (n)
Pregnancy rates below and above 11 mm endometrial thickness
Endometrial thickness on day of HCG
Group A (n)
Group B (n)
< 11 mm
≥ 11 mm
This study is to our knowledge so far the largest in regards to sample size that addresses the effect of endometrial thickness on PR. The day of the stimulation cycle on which the endometrial thickness is measured to document adequate endometrial development has varied between authors. The most often used is the measurement taken on the day of hCG administration, but some authors have used the measurement that was taken on the day of oocyte retrieval or the day of embryo transfer in their studies, which makes it difficult to compare between studies. We have used the measurement taken on the day of hCG administration in our data. The change in endometrial thickness occurring during IVF stimulation has been evaluated by several authors [8, 13, 14]. Grant et al 2007, demonstrated a trend toward significance in the overall change in endometrial thickness between the baseline and that on hCG day . Our results are with agreement to those that reported a positive correlation [3, 4, 10–21]. Endometrial thickness measured on the day of hCG administration was higher in cycles where pregnancy was achieved (mean 11.6 vs. 11.3 mm, respectively, p < 0.0001), but the difference is not of clinical significance, because results fell within the range of measurement error. When using a multiple logistic regression analysis to control all other confounding variables, we found an independent effect of endometrial thickness on PR. The uniqueness of this study is that it demonstrated a steady and gradual increase in PR as endometrial thickness increases. Many previous studies reported significant differences in PRs above and below a threshold thickness of 8 – 10 mm, but didn't show a continuous relationship such as we found [3, 4, 11, 12, 19]. Although we found a clear positive correlation between endometrial thickness and PR, our PR was 29.4% among patients with ≤ 6 mm endometrial thickness in contrast to Gonen et al 1990 who reported poor PR with endometrial thickness < 6 mm . Furthermore, there were several reports of successful pregnancies resulting from cycles with endometrial thickness of ≤ 4 mm  indicating that a thin endometrium does not necessarily preclude the possibility of implantation. Hence cancellation of cycle based on a thin endometrium is unwarranted.
Some authors suggested a detrimental effect of endometrial thickness of ≥ 14 mm on PR . Our results on the contrary, suggest that PRs are highest for patients with the thickest lining, and are consistent with other recent studies finding no reduction in PRs with very thick endometrium [16, 23–25]. In fact there was a case report of a successful twin pregnancy after IVF with an endometrial thickness of 20 mm . Limitations of our study, it is retrospective in nature, but all patients received hMG for stimulation, hence eliminating the bias that can result from different stimulation medications and their different effects on endometrial proliferation. Similarily the number of embryos transferred was limited to two, unless there was only one embryo available for transfer, to control its effect on PR. The poor predictive value of the ROC analysis makes it difficult to accurately determine a cut-off value, never the less, adequate endometrial development is required for pregnancy to occur, and PR were found to be higher when the endometrium reached at least 11 mm thickness.
The results of the present study identified a positive linear correlation between endometrial thickness measured on hCG day and PR. Therefore, clinicians must pay close attention to endometrial development as well as to follicle growth. But again cancellation of embryo transfer based on a thin endometrial lining is unwarranted.
We would like to thank Dr Mohamed Gamal El Din Hassan (PhD) Scientist/Biostatistician from Biostatistics, Epidemiology and Scientific Computing (BESC), Research Center KFSHRC) for his help in the statistical analysis.
- Freidler S, Schenker JG, Herman A, Lewin A: The role of ultrasonography in the endometrial receptivity following assisted reproduction treatmens: a critical review. Hum Reprod Update. 1996, 2: 323-335. 10.1093/humupd/2.4.323.View ArticleGoogle Scholar
- Isaacs JD, Wells CS, Williams DB, Odem RR, Gast MJ, Strickler RC: Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone. Fertil Steril. 1996, 65: 262-266.PubMedGoogle Scholar
- Noyes N, Liu HC, Sultan K, Schattman G, Rosenwaks Z: Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization. Hum Reprod. 1995, 10: 919-922.PubMedGoogle Scholar
- Rinaldi L, Lisi F, Floccari A, Lisi R, Pepe G, Fishel S: Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. Hum Reprod. 1996, 11: 1538-1541.View ArticlePubMedGoogle Scholar
- Yuval Y, Lipitz S, Dor J, Achiron R: The relationships between endometrial thickness, and blood flow and pregnancy rates in in-vitro fertilization. Hum Reprod. 1999, 14: 1067-1071. 10.1093/humrep/14.4.1067.View ArticlePubMedGoogle Scholar
- 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, 71: 147-149. 10.1016/S0015-0282(98)00413-0.View ArticlePubMedGoogle Scholar
- De Geyter C, Schmitter M, De Geyter M, Nieschlag E, Holzgreve W, Schneider HP: Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women. Fertil Steril. 2000, 73: 106-113. 10.1016/S0015-0282(99)00484-7.View ArticlePubMedGoogle Scholar
- Bassil S: Changes in endometrial thickness, thickness, length and pattern in predicting pregnancy outcome during ovarian stimulation in in vitro fertilization. Ultrasound Obstet Gynecol. 2001, 18: 258-263. 10.1046/j.1469-0705.2001.00502.x.View ArticlePubMedGoogle Scholar
- Schild RL, Knobloch C, Dorn C, Fimmers R, Ven van der H, Hansmann M: Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow. Fertil Steril. 2001, 75: 361-366. 10.1016/S0015-0282(00)01695-2.View ArticlePubMedGoogle Scholar
- Kovacs P, Matyas S, Boda K, Kaali SG: The effect of endometrial thickness on IVF/ICSI outcome. Hum Reprod. 2003, 18: 2337-2341. 10.1093/humrep/deg461.View ArticlePubMedGoogle Scholar
- Check JH, Nowroozi K, Choe J, Dietterich C: Influence of endometrial thickness and echo patterns on pregnancy rates during in vitro fertilization. Fertil Steril. 1991, 56: 1173-1175.PubMedGoogle Scholar
- Dickey RP, Olar TT, Curole DN, Taylor SN, Rye PH: Endometrial pattern and thickness associated with pregnancy outcome after assisted reproduction technologies. Hum Reprod. 1992, 7: 418-421.PubMedGoogle Scholar
- Gonen Y, Casper RF, 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.PubMedGoogle Scholar
- Gonen Y, Casper RF: Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF). J In Vitro Fert Embryo Transfer. 1990, 7: 146-152. 10.1007/BF01135678.View ArticleGoogle Scholar
- McWilliams Grant, Frattarelli John: Changes in measured endometrial thickness predict in vitro fertilization success. Fertil Steril. 2007, 88: 74-81. 10.1016/j.fertnstert.2006.11.089.View ArticlePubMedGoogle Scholar
- Sher G, Herbert C, Maassarani G, Jacobs MH: Assessment of the late proliferative phase endometrium by ultrasonography in patients undergoing in-vitro fertilization and embryo transfer (IVF/ET). Hum Reprod. 1991, 6: 232-237.PubMedGoogle Scholar
- Glissant A, de Mouzon J, Frydman R: Ultrasound study of the endometrium during in vitro fertilization cycles. Fertil Steril. 1985, 44: 786-790.PubMedGoogle Scholar
- Zhang Xingpi, Chen Chi-Huang, Confino Edmond, Barnes Randall, Milad Magdy, Kazer Ralph: Increased endometrial thickness is associated with improved treatment outcome for selected patients undergoing in vitro fertilization – embryo transfer. Fertil Steril. 2005, 83: 336-340. 10.1016/j.fertnstert.2004.09.020.View ArticlePubMedGoogle Scholar
- Check JH, Nowroozi K, Choe J, Lurie D, Dietterich C: The effect of endometrial thickness and echo pattern on in-vitro fertilization outcome in donor oocyte-embryo transfer cycle. Fertil Steril. 1993, 59: 72-75.PubMedGoogle Scholar
- Wiser Amir, Baum Micha, Hourwitz Ariel, Lerner-Geva Liat, Dor Jehoshua, Shulman Adrian: Predicting factors for endometrial thickness during treatment with assisted reproductive technology. Fertil Steril. 2007, 87: 799-804. 10.1016/j.fertnstert.2006.11.002.View ArticleGoogle Scholar
- Richter Kevin, Bugge Kathleen, Bromer Jason, Levy Michael: Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril. 2007, 87: 53-59. 10.1016/j.fertnstert.2006.05.064.View ArticlePubMedGoogle Scholar
- Sundstrom P: Establishment of a successful pregnancy following in vitro fertilization with an endometrial thickness of no more than 4 mm. Hum Reprod. 1998, 13: 1550-1552. 10.1093/humrep/13.6.1550.View ArticlePubMedGoogle Scholar
- Yakin K, Akarsa C, Kahraman S: Cycle lumping or sampling – a witches' brew?. Fertil Steril. 2000, 73: 175-10.1016/S0015-0282(99)00430-6.View ArticlePubMedGoogle Scholar
- Dietterich C, Check JH, Choe JK, Nazari A, Lurie D: Increased endometrial thickness on the day of human chorionic gonadotropin (hCG) injection does not adversely effect pregnancy or implantation rates following in vitro fertilization-embryo transfer (IVF-ET). Fertil Steril. 2002, 77: 781-786. 10.1016/S0015-0282(01)03276-9.View ArticlePubMedGoogle Scholar
- Yoeli R, Ashkenazi J, Orvieto R, Shelef M, Kaplan B, Bar-Hava I: Significance of increased endometrial thickness in assisted reproduction technology treatments. J Assist Reprod Genet. 2004, 21: 285-289. 10.1023/B:JARG.0000043701.22835.56.PubMed CentralView ArticlePubMedGoogle Scholar
- Quintero RB, Sharara FI, Milki AA: Successful pregnancies in the setting of exaggerated endometrial thickness. Fertil Steril. 2004, 82: 215-217. 10.1016/j.fertnstert.2004.02.099.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.