Skip to main content
Download PDF

Suitable endometrial thickness on embryo transfer day may reduce ectopic pregnancy rate and improve clinical pregnancy rate

BMC Pregnancy and Childbirth volume 23, Article number: 517 (2023) Cite this article

Abstract

Background

This retrospective study aimed to investigate the most suitable endometrial thickness (EMT) on the day of embryo transfer that could reduce ectopic pregnancy rate (EPR) and improve clinical pregnancy rate (CPR) in fresh embryo transfer patients with early follicular phase long-acting regimen.

Methods

A total of 11,738 IVF/ICSI cycles, comprising 4,489 non-clinical pregnancies, 7,121 intrauterine pregnancies, and 128 ectopic pregnancy cycles after fresh embryo transfer, recorded between September 2017 and December 2020. Clinical pregnancy (CP) and ectopic pregnancy (EP) were the primary outcomes. Multivariate logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for EP and CP. Patients were divided into three groups based on the EMT (6–10 mm, 11–15 mm, and 16–20 mm). CPR and EPR per millimeter of EMT were drawn into a line chart, and three groups were analyzed by Chi-square test.

Results

After controlling for potential confounders, EMT had a significant effect on CP (aOR = 1.07; 95% CI, 1.05–1.08; P = 0.00) and EP (aOR = 0.88; 95% CI, 0.82–0.94; P = 0.00). With the increase of EMT, CPR increased and EPR decreased. Pearson correlation coefficients were r = 0.708 (P = 0.00) and r =-0.558 (P = 0.03), respectively. Significant differenceswere detected in the CPRs and EPRs (all P = 0.00). The CPR in the 6–10 mm group (54.88%) was significantly lower than that in the 11–15 mm group (64.23%) and the 16–20 mm group (64.40%) (P = 0.00). The EPR in the 6–10 mm group (2.72%) was significantly higher than that in the other two groups (1.60% and 0.97%, P = 0.00). The difference in CPR and EPR between the 11–15 mm group and the 16–20 mm group was not statistically significant, which indicated that EMT ≥ 11 mm simultaneously reduced the EPR and increased the CPR.

Conclusions

EMT was inversely proportional to EPR and directly proportional to CPR in fresh embryo transfer cycles. The EMT ≥ 11 mm on the day of embryo transfer could simultaneously achieve lower EPR and higher CPR. Accordingly, more attention should be given to the EMT of women who underwent ART treatment.

Peer Review reports

Background

With the rapid development of assisted reproductive technology (ART), the clinical pregnancy rates (CPR) have substantially improved; however, the incidence of ectopic pregnancy (EP) is increasing. The ectopic pregnancy in IVF/ICSI cycle, which was reported to be 2.1%-8.6% [1, 2], is more frequent than 1–2% [3] observed in the natural pregnancy group, thus suggesting that ART independently increases the EP risk [4]. Furthermore, 95% of EP occurs in the fallopian tubes, resulting in the injury and removal of reproductive organs such as fallopian tubes. In some severe cases, it may even lead to early maternal death [5], thus causing a heavy psychological and economic burden. Multiple factors may be responsible for the high rate of EP during the IVF/ICSI, EP history, tubal factors, pelvic lesions, smoking, ART procedures, and similar [6,7,8,9].

Endometrial thickness (EMT) is a frequently monitored indicator in the IVF/ICSI process and an indirect indicator of endometrial receptivity. Several studies have focused on the EMT in terms of the relationship between the EMT and pregnancy outcome, placenta previa risk and birth weight, etc. Existing studies have shown that the EMT is positively correlated with the CPR in the IVF/ICSI [10,11,12,13]. On the contrary, some believe that the EMT is not associated with CPR [13, 14] and is a poor predictor of CPR [15, 16]. Yuan et al. [11] reported that the EMT was a statistically significant predictor of CP and EP. Rombauts et al. demonstrated that thin endometrium is an independent risk factor for EP, and patients with EMT < 9 mm have four times the EP risk of > 12 mm [17]. Another research also confirmed that EMT > 12 mm can reduce the risk of EP [18]. In contrast, a meta-analysis concluded that the EMT did not affect on the EP outcome [12].

The relationship between EMT, CP, and EP is controversial and inconclusive. In addition, there were no clear guidelines for recommendations on the EMT for reducing the EPR and increasing the CPR. Therefore, further discussion and research are needed. Our study focused on exploring the factor(s), which could simultaneously improve CPR and reduce EPR in fresh embryo transfer patients with early follicular phase long-acting regimens. First, we utilized a large sample size to define the risk factor(s) in EP and CP. Next, we identified EMT as the intrinsic factor that may be predictive in obtaining better pregnancy outcomes. Ultimately, we determined which EMT range can attain lower EPR and higher CPR.

Methods

Study design

This retrospective study was based on 14,879 IVF/ICSI fresh cycles recorded at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University between September 2017 and December 2020. Patients with early follicular phase long-acting regimens were included. The exclusion criteria were as follows: embryo transfer except on the D3 or D5; patients with uterine malformation or endometriosis; genetic factors infertility. After screening for exclusion criteria, 11,738 IVF/ICSI fresh cycles were included, comprising 4,489 non-clinical pregnancies, 7,121 intrauterine pregnancies, and 124 ectopic and 4 heterotopic pregnancies cycles (1.77%), as shown in the patients' selection flow chart (Fig. 1).

Fig. 1
figure 1

Patients’ selection flowchart

Full size image

This retrospective study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University. (reference number: 2022-KY-0340–002).

Definition of clinical outcomes

The primary outcome measures were clinical pregnancy (CP) and ectopic pregnancy (EP). Biochemical pregnancy referred to pregnancy confirmed only by positive detection of hCG in serum or urine [19], determined at 14 or 18 days after embryo transplantation in our center. The CP was defined as pregnancy confirmed by ultrasound showing one or more pregnancy sacs [19]. Patients with biochemical pregnancy were confirmed by b-ultrasound reexamination at 35 days after an embryo transfer in our center. CPs were divided into intrauterine (IUP) and ectopic (EP) pregnancies. The IUP referred to the presence of the sac inside the uterus, and EP referred to the presence of the sac outside the uterus. Heterotopic pregnancy referred to the presence of a pregnancy sac, both intrauterine and extrauterine, also classified as the EP. The CPR was defined as the number of clinical pregnancies per 100 embryo transfer cycles, while the EPR was defined as the number of EP cycles per 100 clinical pregnancy cycles after embryo transfer. The EMT was measured on the midsagittal plane of the uterine body on the day of embryo transfer to measure the maximum thickness of the endometrium-muscularum junction from one interface to the other.

The spontaneous cessation of an intrauterine pregnancy before the completion of 22 weeks of gestation was known as spontaneous abortion. Missed miscarriage was defined as spontaneous loss of a clinical pregnancy before 22 weeks of gestational age, in which the embryo(s) or fetus(es) was/were nonviable and was/were not spontaneously absorbed or expelled from the uterus. Induced abortion referred to intentional loss of an intrauterine pregnancy, through intervention by medical, surgical or unspecified means. Preterm birth was defined as a birth that occured after 22 weeks and before 37 consecutive weeks of gestation.

ART protocols and embryo assessment

Our patients were fresh embryo transfer patients with the early follicular phase long-acting regimen. Patients were injected with 3.75 mg of long-acting gonadotropin-releasing hormone agonist (GnRH-a, Diphereline, Ipsen, France) on day 2 of menstruation. Patients meeting reduced criteria were initiated with gonadotropin (Gn), usually recombinant follicle-stimulating hormone (r-FSH, Pouliquen, Merck Sharp & Dohme, USA) or human menopausal gonadotropins (HMG, Menopur, Hui Ling, Switzerland) to stimulate follicle growth within 30 to 40 days after injection. The down-regulated criteria were FSH < 5 mIU/mL, LH < 5 mIU/mL, E2 < 50 pg/ mL and EMT ≤ 5 mm. When ≥ 2 follicles reached a diameter of ≥ 18 mm or more than 2/3 of follicles reached ≥ 16 mm, ovulation was triggered by Aizer (250 µg, Merck Serono, Italy) or hCG (2,000 IU, Lizhu Medicine). Transvaginal ultrasound-guided oocyte retrieval was conducted approximately 37 h later. Depending on the patient's condition and embryo development, one or two D3/D5 embryo(s) were selected for transfer. Luteal support was initiated on the day of oocyte retrieval with daily transvaginal progesterone (Xenotong, Merck Serono, Switzerland) and oral progesterone (30 mg/d, Dupbaston, Abbott, Holland).

Day 3 embryos are graded employing Peter's criteria in our center based on the number, size, average degree, refractive index, and blastomere fragmentation [20]. Top-quality embryos were those classified as Grade I and II. On day 5, blastocysts were morphologically evaluated and scored utilizing Gardner's standard for blastocyst stage, inner cell mass (ICM) and trophectoderm (TE) [21]. The final choice to transfer fresh embryos was based on ultrasound results on the morning of day 3 or day 5.

Statistical analysis and analyzed variables

Based on previously published articles and clinical experience, the following factors were analyzed in the present study: female age; female body mass index (BMI); basal follicle-stimulating hormone (FSH); infertility factor types; EMT on the day of embryo transfer; fertilization method (IVF or ICSI); the developmental days of transplanted embryos (D3 or D5); the number of embryos transferred (1 or 2); cycle number (1 or ≥ 2); and laboratory indicators (egg count; MII rate; 2PN rate; high-quality embryo rate; blastocyst formation rate).

Data were analyzed by SPSS25.0 software. The quantitative data were recorded as mean ± standard deviation (SD). The continuous variables with normal distribution were compared using Student’s t-test, while those with non-normal distribution were compared using the Wilcoxon rank-sum test. Qualitative data were recorded as frequency and percentage (%), and frequencies were compared using the Chi-square test or Fisher's exact test. We included all possible variables and included baseline comparisons of laboratory data that have not been addressed by previous studies. Data were analyzed with the multivariate logistic regression to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for CP and EP to control potential confounders and analyze the risk factors of the CP and EP. The CPR and EPR per millimeter of EMT were drawn into a line chart, and three groups were analyzed by Chi-square test. P < 0.05 was considered statistically significant.

Results

Predictive factors associated with CP and EP

The basic characteristics of all patients and cycles are shown in Table 1. The outcome variables were CP (Table 1) and EP (Table 2) separately. There were significant differences in female age, fallopian tube factors, polycystic ovary syndrome (PCOS), ovarian dysfunction, endometrial thickness, embryo transfer stage, the number of transplanted embryos, cycle number, and all laboratory data between the non-CP group and CP group (all P < 0.05). In contrast, significant differences were only found in tubal factors, EMT, and fertilization method between IUP and EP groups (all P < 0.05). Patients with tubal factors, thinner endometrium, or using IVF had a higher risk of EP, while many factors had no significant effect on EP (P > 0.05), including age, BMI, basal FSH, ovarian dysfunction, male factors, embryo transfer stage (D3 or D5), embryo transfer number, cycle number, and laboratory data.

Table 1 Basic characteristics with CP
Full size table
Table 2 Basic characteristics with EP
Full size table

In order to investigate the influencing factors of CP and EP, the multivariate logistic regression analysis was performed. All variables with P < 0.1 in the univariate analysis were included in the multivariate regression analysis (Tables 3 and 4). The results confirmed that the older age led to lower clinical pregnancy rate (aOR = 0.92; 95% CI, 0.91–0.93; P = 0.00). Patients with PCOS increased the risk of clinical pregnancy by 51% (aOR = 1.51; 95% CI, 1.30–1.77; P = 0.00). The probability of CP was reduced by 40% in patients with ovarian dysfunction (aOR = 0.60; 95% CI, 0.46–0.80; P = 0.00). The D5 embryo transfer was associated with a 52% increase in CPR compared with D3 (aOR = 0.66; 95% CI, 0.56–0.78; P = 0.00). Compared with single embryo transfer, double embryo transfer increased the CPR by about 1.4 times (aOR = 2.38; 95% CI, 2.06–2.75; P = 0.00). A high rate of 2PN (aOR = 1.50; 95% CI, 1.14–1.99; P = 0.00), high quality embryo rate (aOR = 1.75; 95% CI, 1.45–2.11; P = 0.00), blastocyst formation rate (aOR = 1.62; 95% CI, 1.41–1.87; P = 0.00) all promoted CP. Tubal factors resulted as risk factors for EP, increasing the risk of EP by 49% (aOR = 1.49; 95% CI, 1.01–2.18; P = 0.04). After controlling for potential confounding factors, EMT had a significant effect on the CP (aOR = 1.07; 95% CI, 1.05–1.08; P = 0.00) and the EP (aOR = 0.88; 95% CI, 0.82–0.94; P = 0.00). It can be concluded that the thicker intima, the higher the probability of CP, and the lower EP risk.

Table 3 Multivariate logistic regression analysis with CP
Full size table
Table 4 Multivariate logistic regression analysis with EP
Full size table

The distribution of EMT

The distribution of EMT on the day of embryo transfer is shown in detail in Fig. 2. Mean (± SD) and median EMT were 12.34 (± 2.70) and 12.00, respectively. P1 = 6 mm, P10 = 9 mm, P25 = 11 mm, P50 = 12 mm, P75 = 14 mm, P90 = 16 mm, P99 = 20 mm. Also, 98% patients had EMT between 6–20 mm.

Fig. 2
figure 2

Distribution of patients by endometrial thickness on the day of embryo transfer

Full size image

CPR and EPR by per mm EMT and EMT groups

The line charts of CPR (Fig. 3A) and EPR (Fig. 3B) per mm of EMT within the range of 6–20 mm had followed certain rules. With the increase of EMT, CPR increased and EPR decreased. The Pearson’s coefficient showed a significant association (P < 0.05) of EMT with CPR (r = 0.708 (high correlation, P = 0.003) and EPR (r =-0.558, medium correlation, P = 0.031). The linear regression models were CPR = 0.019 × EMT + 0.327 (P = 0.003) and EPR = -0.007 × EMT + 0.12 (P = 0.031). The CPR gradually increased at 6–10 mm, while it reached a platform area at ≥ 11 mm and gradually stabilized at 60% -70%, but then slightly declined at 16–19 mm. The EPR gradually declined at 6–10 mm, while it was roughly stable at 1%-2% when EMT ≥ 11 mm, although some values were outside the range. Additionally, line charts of live birth rate and early miscarriage rate per mm remained stable at ≥ 11 mm as shown in Figure S1.

Fig. 3
figure 3

A CPR by per mm EMT. CPR, clinical pregnancy rate. B EPR by per mm EMT. EPR, ectopic pregnancy rate

Full size image

The comparison of CPR and EPR by EMT groups is described in Fig. 4. Significant differences were observed between CPR and EPR groups (P = 0.00). The CPR in the 6–10 mm group (54.88%) was significantly lower than that in the 11-15 mm group (64.23%) and the 16–20 mm group (64.40%) (P = 0.00), while EPR in the 6-10 mm group (2.72%) was significantly higher than that in the other two groups (1.60% and 0.97%, P = 0.00). Notably, the differences in CPR and EPR between the 11–15 mm group and the 16—20 mm group were not statistically significant, which indicated that EMT ≥ 11 mm simultaneously tended toward higher CPR and lower EPR.

Fig. 4
figure 4

Comparisons of CPR and EPR by EMT groups. *P < 0.01. NS = not significant. CPR, clinical pregnancy rate; EPR, ectopic pregnancy rate

Full size image

Discussion

In this large retrospective study, we analyzed 11,738 IVF/ICSI cycles aiming to identify the influencing factors of CPR and EPR in the IVF/ICSI so as to better define appropriate EMT on the day of embryo transfer to achieve better pregnancy outcomes. Our results confirmed that compared to EMT < 11 mm, the CPR was higher, and the EPR was lower when EMT ≥ 11 mm on the day of embryo transfer. In fact, after adjusting for all possible confounding factors, the impact of EMT on the day of ET persisted.

Our findings indicated that older age, thin endometrium, and ovarian dysfunction were the hindering factors for CP, while D5 embryo transfer, PCOS, double embryo transfer, high 2PN rate, high-quality embryo rate and blastocyst formation rate all promoted CP. Numerous studies have demonstrated that age is inversely correlated with CPR after IVF/ICSI [22]. The older the patients are, the worse the ovarian function, the worse the quality and quantity of oocytes and embryos, the thinner the endometrium, and the greater the obstacle to successful CP [14]. D5 embryo transfer has been identified as a definite CP promotion factor [23], corroborating that blastocyst formation rate is directly proportional to the CPR. Our results revealed that a high-quality embryo rate which represents the embryo quality was positively correlated with CPR, as shown by a previous study [24]. It was reported that the CPR and live birth rate of double embryo transfer was much higher than that of single embryo transfer [25]; nonetheless, opposite findings were also reported [26]. However, as double embryo transfer fortifies the risk of premature birth, low birth weight, cerebral palsy, and similar, elective single-embryo transfer (eSET) was advocated as the most effective mean to avoid multiple gestations in IVF cycles [27, 28].

The findings of this paper yield a puzzling result that PCOS could promote clinical pregnancy. Despite the fact that PCOS patients are at a greater risk of infertility due to ovulation abnormalities, they have an advantage in ovarian reserve [29]. The largest retrospective investigation on PCOS revealed that individuals aged 20–44 had considerably greater mean number of oocytes retrieved, clinical pregnancy and live-birth rates than the control group [30]. This has also been supported by previous investigations [31, 32]. Increased oocytes retrieved paves the way for more highly qualified embryos. The present study's results that PCOS encourages clinical pregnancy can also be explained by those aforementioned findings. Additionally, we compared PCOS patients with non-PCOS patients to confirm this and discovered that PCOS patients were younger in age (29.28 ± 3.78 vs 31.53 ± 4.90, P = 0.00), had higher number of oocytes retrieved (15.57 ± 5.73 vs 12.57 ± 5.70, P = 0.00), more high-quality embryos (6.96 ± 3.97 vs 5.46 ± 3.58, P = 0.00) and higher CPR (74.1% vs 60.4%, P = 0.00). These findings line up with the research mentioned above.

It was found that EMT and tubal infertility were independent risk factors for EP, while fertilization method, embryo development days (D3 or D5), and a number of transferred embryos had a futile effect on the EP. Several studies have concluded that D5 and D3 fresh embryo transfer made no difference in EP risk [18, 23]. BMI and PCOS were not significantly correlated with EP in the present study, which was consistent with previous studies [33, 34]. Tubal infertility, which was identified as an important risk factor for the EP during IVF-ET [35]. Due to controlled ovarian hyperstimulation (COH) during the IVF/ICSI, high estrogen status may influence uterine receptivity and tubal status leading to higher EP rates [36]. Moreover, the relatively higher E-cadherin expression, a kind of cell adhesion molecule mediating embryo implantation at the fallopian tube in the IVF/ICSI patients, is another possible reason [37].

Multiple studies have reported that thin endometrium is associated with lower CPR and higher EPR [10, 11, 17, 18, 38, 39], which is also consistent with our findings. The reasons why thin endometrium leads to higher EPR and lower CPR are complex and undetermined. One is the effect of oxygen tension, where implanted embryos are closer to the spiral arteries in the basal endometrium layer due to thin or absent uterine functional layer, which results in exposure to higher oxygen concentration that restrains their growth [40]. Furthermore, abnormal uterine peristalsis may increase the risk of the embryo being dislodged from its original transfer position, which may increase the likelihood of EP [41, 42].

It was found that the EMT ≥ 11 mm on the embryo transfer day could simultaneously achieve lower EPR and higher CPR in the present study, supported by a number of other observations. Fang et al. [39] demonstrated that EP risk was reduced by about 50% when EMT was > 10 mm. The cut-off value of EMT as a possible predictor of IUP was 10 mm(AUC = 0.69) [43]. Rombauts and colleagues [17] found that patients with an EMT > 12 mm had a threefold lower risk of developing EP compared with patients with an EMT < 9 mm. Similarly, patients with EMT > 12 mm had a lower EP risk [18]. In the present study, patients with a 4 mm EMT achieved CP, while there are previous reports of CP with an EMT of 4 mm and 4.8 mm [44]. Patients with thin endometrium could realize pregnancy, but the EP risk is relatively high. Nevertheless, there is still a high CPR when EMT < 11 mm. A large EMT (> 14 mm) had no adverse effect on the CPR, which is in line with previous studies [10]. Still, it was reported that the CPR significantly decreased when EMT > 14 mm [45], and patients with EMT > 12 mm had a fourfold higher risk of placenta previa than those with EMT < 9 mm [46]. Therefore, it is imperative that patients pursue an appropriate EMT, and the findings in the present study counsel that patients with an EMT of 11 mm or greater have a higher chance of CP and a lower risk of EP.

The timing of EMT measurements has been described variously in the literature of EMT and IVF-ET outcome studies, and the ideal moment of measurement representing endometrial receptivity remains contentious. Less research has chosen the ET day, while the majority of studies have picked the day of hCG or oocyte retrieval for endometrial assessment. An increasing ET day EMT has been exhibited in earlier research to favor pregnancy outcome in both fresh and FET cycles [47]. According to a recent meta-analysis, ET day EMT is a somewhat unreliable prospective indicator of pregnancy outcomes [15]. As opposed to oocyte retrieval day and ET day, Dechaud et al.'s research [48] observed that endometrial assessment on the day of the hCG injection was more pertinent to the clinical pregnancy outcome. Undeniably, the endometrium on the ET day is the one with which the transferred embryo came into direct contact. The EMT on the ET day of patients with fresh embryo transfer is routinely measured in our center. Few studies have explored the relationship between ET day endometrium and ectopic pregnancy, to which we added that the relationship between ET day EMT and EP is consistent with other studies.

Strengths and limitations

We believe that EMT on the ET day is when the endometrial environment is directly contacted by the transferred embryo, which can reduce the influence of confounding factors such as possible endometrial changes, thus making comparative analysis more reliable. Additionally, this study has strict standards of arrangement, a large sample size, and a wide range of EMT. All included patients were fresh embryo transfer patients with the early follicular phase long-acting regimen, which reinforced the statistical reliability. A single-center study reduced variability between centers. Unlike other studies, this study focused on the suitable EMT that simultaneously resulted in a lower EPR and a higher CPR.

One limitation of the present study is related to its observational nature that is associated with some inevitable shortcomings and does not take all the confounding factors such as race, transfer fluid volume, and transferring depth etc. [4] into account. Smoking is a well-known confounding factor that was not recorded in the data, but the number of patients who smoked was so small that it should not have affected the results. In addition, although there are uniform standards for single-center trained sonographers, there were some differences between individuals. Besides, there may be selection bias considering the population was from a single center. Consequently, future multi-center studies are needed to further confirm reported results.

Conclusion

EMT resulted inversely proportional to EPR and directly proportional to CPR in fresh embryo transfer cycles. The EMT ≥ 11 mm on the embryo transfer day could simultaneously achieve lower EPR and higher CPR. Future studies are needed to evaluate the predictive validity of EMT and to validate the applicability to other regimes of IVF/ICSI.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Santos-Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Human Reprod (Oxford, England). 2016;31(2):393–402.

    Google Scholar 

  2. Juneau C, Bates G. Reproductive outcomes after medical and surgical management of ectopic pregnancy. Clin Obstet Gynecol. 2012;55(2):455–60.

    Article  PubMed  Google Scholar 

  3. Hendriks E, Rosenberg R, Prine L. Ectopic Pregnancy: Diagnosis and Management. Am Fam Physician. 2020;101(10):599–606.

    PubMed  Google Scholar 

  4. Perkins KM, Boulet SL, Kissin DM, Jamieson DJ. Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001–2011. Obstet Gynecol. 2015;125(1):70–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brady P. New Evidence to Guide Ectopic Pregnancy Diagnosis and Management. Obstet Gynecol Surv. 2017;72(10):618–25.

    Article  PubMed  Google Scholar 

  6. ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol. 2018;131(3):e91–103.

    Article  Google Scholar 

  7. Londra L, Moreau C, Strobino D, Bhasin A, Zhao Y. Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization? Fertil steril. 2016;106(3):666–72.

    Article  CAS  PubMed  Google Scholar 

  8. Lin S, Li R, Zheng X, Chi H, Ren X, Yang R, et al. Influence of embryo culture medium on incidence of ectopic pregnancy in in vitro fertilization. Fertil steril. 2015;104(6):1442–5.

    Article  PubMed  Google Scholar 

  9. Schippert C, Soergel P, Staboulidou I, Bassler C, Gagalick S, Hillemanns P, et al. The risk of ectopic pregnancy following tubal reconstructive microsurgery and assisted reproductive technology procedures. Arch Gynecol Obstet. 2012;285(3):863–71.

    Article  PubMed  Google Scholar 

  10. Ma N, Chen L, Dai W, Bu Z, Hu L, Sun Y. Influence of endometrial thickness on treatment outcomes following in vitro fertilization/intracytoplasmic sperm injection. Reprod Biol Endocrinol: RB&E. 2017;15(1):5.

    Article  Google Scholar 

  11. Yuan X, Saravelos SH, Wang Q, Xu Y, Li TC, Zhou C. Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF-ICSI cycles. Reprod Biomed Online. 2016;33(2):197–205.

    Article  PubMed  Google Scholar 

  12. Gao G, Cui X, Li S, Ding P, Zhang S, Zhang Y. Endometrial thickness and IVF cycle outcomes: a meta-analysis. Reprod Biomed Online. 2020;40(1):124–33.

    Article  PubMed  Google Scholar 

  13. Zhao J, Zhang Q, Wang Y, Li Y. Endometrial pattern, thickness and growth in predicting pregnancy outcome following 3319 IVF cycle. Reprod Biomed Online. 2014;29(3):291–8.

    Article  PubMed  Google Scholar 

  14. Chen SL, Wu FR, Luo C, Chen X, Shi XY, Zheng HY, et al. Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study. Reproduct Biol Endocrinol. 2010;8:30.

    Article  Google Scholar 

  15. Griesinger G, Trevisan S, Cometti B. Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome. Human Reprod Open. 2018; 2018(1):hox031.

  16. Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(4):530–41.

    Article  PubMed  Google Scholar 

  17. Rombauts L, McMaster R, Motteram C, Fernando S. Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles. Hum Reprod. 2015;30(12):2846–52.

    CAS  PubMed  Google Scholar 

  18. Liu X, Qu P, Bai H, Shi W, Shi J. Endometrial thickness as a predictor of ectopic pregnancy in 1125 in vitro fertilization-embryo transfer cycles: a matched case-control study. Arch Gynecol Obstet. 2019;300(6):1797–803.

    Article  CAS  PubMed  Google Scholar 

  19. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Human reproduction (Oxford, England). 2017;32(9):1786–801.

    Article  PubMed  Google Scholar 

  20. Davis OK, Brinsden, P.R. A Textbook of In Vitro Fertilization and Assisted Reproduction. The Parthenon Publishing Group. 1999; New York.

  21. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Reprint of: Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertility and sterility. 2019; 112(4 Suppl1):e81-e4.

  22. Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, et al. Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update. 2013;19(1):26–36.

    Article  PubMed  Google Scholar 

  23. Fang C, Huang R, Wei LN, Jia L. Frozen-thawed day 5 blastocyst transfer is associated with a lower risk of ectopic pregnancy than day 3 transfer and fresh transfer. Fertil Steril. 2015;103(3):655-61.e3.

    Article  PubMed  Google Scholar 

  24. Laasch C, Puscheck E. Cumulative embryo score, not endometrial thickness, is best for pregnancy prediction in IVF. J Assist Reprod Genet. 2004;21(2):47–50.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pandian Z, Marjoribanks J, Ozturk O, Serour G, Bhattacharya S. Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev. 2013; 2013(7):Cd003416.

  26. Luke B, Brown MB, Wantman E, Stern JE, Baker VL, Widra E, et al. Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle. Am J Obstet Gynecol. 2015;212(5):676.e1-7.

    Article  PubMed  Google Scholar 

  27. Coetsier T, Dhont M. Avoiding multiple pregnancies in in-vitro fertilization: who’s afraid of single embryo transfer? Human Reprod (Oxford, England). 1998;13(1o):2663–4.

    Article  CAS  Google Scholar 

  28. Practice Committee of Society for Assisted Reproductive Technology. Practice Committee of American Society for Reproductive Medicine. Elective single-embryo transfer Fertility and sterility. 2012;97(4):835–42.

  29. Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K, et al. Formation and early development of follicles in the polycystic ovary. Lancet (London, England). 2003;362(9389):1017–21.

    Article  CAS  PubMed  Google Scholar 

  30. Kalra SK, Ratcliffe SJ, Dokras A. Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the Society for Assisted Reproductive Technology registry to assess the impact of reproductive aging on live-birth rate. Fertil Steril. 2013;100(1):208–13.

    Article  PubMed  Google Scholar 

  31. Tal R, Seifer DB, Khanimov M, Malter HE, Grazi RV, Leader B. Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes. Am J Obstet Gynecol. 2014;211(1):59.e1-8.

    Article  CAS  PubMed  Google Scholar 

  32. Mai Z, Liu M, Pan P, Li L, Huang J, Chen X, et al. Comparison of Cumulative Live Birth Rate Between Aged PCOS Women and Controls in IVF/ICSI Cycles. Front Endocrinol. 2021;12: 724333.

    Article  Google Scholar 

  33. Koning AM, Mutsaerts MA, Kuchenbecker WK, Broekmans FJ, Land JA, Mol BW, et al. Complications and outcome of assisted reproduction technologies in overweight and obese women. Human reproduction (Oxford, England). 2012;27(2):457–67.

    Article  CAS  PubMed  Google Scholar 

  34. Wang J, Wei Y, Diao F, Cui Y, Mao Y, Wang W, et al. The association between polycystic ovary syndrome and ectopic pregnancy after in vitro fertilization and embryo transfer. Am J Obstet Gynecol. 2013;209(2):139.e1-9.

    Article  PubMed  Google Scholar 

  35. Refaat B, Dalton E, Ledger WL. Ectopic pregnancy secondary to in vitro fertilisation-embryo transfer: pathogenic mechanisms and management strategies. Reprod Biol Endocrinol. 2015;13:30.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Coy P, García-Vázquez FA, Visconti PE, Avilés M. Roles of the oviduct in mammalian fertilization. Reproduction (Cambridge, England). 2012;144(6):649–60.

    Article  CAS  PubMed  Google Scholar 

  37. Revel A, Ophir I, Koler M, Achache H, Prus D. Changing etiology of tubal pregnancy following IVF. Human reproduction (Oxford, England). 2008;23(6):1372–6.

    Article  PubMed  Google Scholar 

  38. Liu H, Zhang J, Wang B, Kuang Y. Effect of endometrial thickness on ectopic pregnancy in frozen embryo transfer cycles: an analysis including 17,244 pregnancy cycles. Fertil Steril. 2020;113(1):131–9.

    Article  PubMed  Google Scholar 

  39. Fang T, Chen M, Yu W, Ma T, Su Z, Chan DYL, et al. The predictive value of endometrial thickness in 3117 fresh IVF/ICSI cycles for ectopic pregnancy. J Gynecol Obstetr Human Reprod. 2021;50(8): 102072.

    Article  Google Scholar 

  40. Casper RF. It’s time to pay attention to the endometrium. Fertil Steril. 2011;96(3):519–21.

    Article  PubMed  Google Scholar 

  41. Zhu L, Che HS, Xiao L, Li YP. Uterine peristalsis before embryo transfer affects the chance of clinical pregnancy in fresh and frozen-thawed embryo transfer cycles. Hum Reprod. 2014;29(6):1238–43.

    Article  CAS  PubMed  Google Scholar 

  42. Zhu L, Li Y, Xu A. Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women. Hum Reprod. 2012;27(9):2684–9.

    Article  CAS  PubMed  Google Scholar 

  43. Ellaithy M, Abdelaziz A, Hassan MF. Outcome prediction in pregnancies of unknown location using endometrial thickness measurement: is this of real clinical value? Eur J Obstet Gynecol Reprod Biol. 2013;168(1):68–74.

    Article  PubMed  Google Scholar 

  44. Zhao J, Zhang Q, Li Y. The effect of endometrial thickness and pattern measured by ultrasonography on pregnancy outcomes during IVF-ET cycles. Reprod Biol Endocrinol: RB&E. 2012;10:100.

    Article  Google Scholar 

  45. 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(1):147–9.

    Article  CAS  PubMed  Google Scholar 

  46. Rombauts L, Motteram C, Berkowitz E, Fernando S. Risk of placenta praevia is linked to endometrial thickness in a retrospective cohort study of 4537 singleton assisted reproduction technology births. Human Reprod (Oxford, England). 2014;29(12):2787–93.

    Article  CAS  Google Scholar 

  47. Kovacs P, Matyas S, Boda K, Kaali SG. The effect of endometrial thickness on IVF/ICSI outcome. Human Reprod (Oxford, England). 2003;18(11):2337–41.

    Article  CAS  Google Scholar 

  48. Dechaud H, Bessueille E, Bousquet PJ, Reyftmann L, Hamamah S, Hedon B. Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity to implantation. Reprod Biomed Online. 2008;16(3):368–75.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank to the Chinese Natural Science Funds Youth Funds for providing financial support.

Funding

This work was supported by the Chinese Natural Science Funds Youth Funds (81701505).

Author information

Author notes

  1. Shiming Wang and Lin Qi contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Reproductive Medical Center, Henan Province Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Erqi District, Zhengzhou, China

    Shiming Wang, Lin Qi, Yaping Liu, Hao Shi, Xiaoli Chen, Ningning Wang & Yingchun Su

Authors
  1. Shiming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hao Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoli Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ningning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yingchun Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Lin Qi developed the original concept of this study. Shiming Wang, Lin Qi and Yingchun Su participated in the study design. Shiming Wang, Yaping Liu, Xiaoli Chen, and Ningning Wang participated in data collection, Shiming Wang conducted data analysis and interpretation and the writing of the original version of the manuscript. Hao Shi guided the data analysis and gave guidance. All authors participated in the manuscript revision. All authors have contributed to critical discussion and reviewed the final version.

Corresponding author

Correspondence to Yingchun Su.

Ethics declarations

Ethics approval and consent to participate

We confirm that all methods were carried out in accordance with relevant guidelines and regulations in the Declaration of Helsinki. Written informed consent was obtained from all participants for data use prior to enrollment. This retrospective study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (reference number: 2022-KY-0340–002).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:

  Figure S1. LBR and EMR by per mm EMT. LBR, live birth rate; EMR, early miscarriage rate.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Qi, L., Liu, Y. et al. Suitable endometrial thickness on embryo transfer day may reduce ectopic pregnancy rate and improve clinical pregnancy rate. BMC Pregnancy Childbirth 23, 517 (2023). https://doi.org/10.1186/s12884-023-05837-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12884-023-05837-6

Keywords

BMC Pregnancy and Childbirth

ISSN: 1471-2393

Contact us