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Source publication
Purpose
To investigate the association between endometrial compaction and pregnancy rates in unstimulated natural cycle frozen embryo transfers.
Design
A single-center prospective cohort study. Endometrial thickness by transvaginal ultrasound and blood progesterone levels on the day of ovulation and the day of embryo transfer were evaluated in pat...
Citations
... Youngster and his colleagues showed that the ratio of clinical and ongoing pregnancy was higher in the compacted group, which was consistent with the present study (12). Also, Ju et al. showed that the percentage of clinical pregnancy was higher in the compacted group In this study, clinical pregnancy evaluation was done in patients undergoing frozen-thaw embryo transfer (FET) cycle (13). ...
... Youngster and his colleagues showed that the clinical and chemical pregnancy rate was higher in the compacted group with 10 and 15% compared to 5%. Further investigations showed that an increase of more than 10% compaction does not have much effect on the clinical and chemical pregnancy rate (12). Their results were not consistent with the present study. ...
Background
Today, the thickness of the endometrium as a key factor plays an important role in pregnancy outcomes of infertile patients. Based on this, it has been shown that endometrial compaction affect fertility success in patients. In this study, the impact of endometrial compaction on pregnancy outcomes has been evaluated.
Material and methods
This prospective cohort study included 250 patients undergoing embryo transfer, who referred to the infertility center of Shariati Hospital in Tehran between 2021–2022. They were examined from the point of view of the relationship between endometrial thickness changes and fertility rate in FET and Fresh cycles. After preparing the endometrium, its thickness was evaluated by ultrasound.
Result
The results showed that the percentage of chemical and clinical pregnancy in the compact group was higher compared to the non-compact one, which was statistically significant (p < 0.05). The rate of pregnancy in four groups of 5, 10, 15, and %20 compaction was 77(30.4%), 49(19.4%), 28(11.1%), and 14(5.5%), respectively.
Conclusion
Finally, endometrial compaction can be associated with an increase in chemical and clinical pregnancy rate in infertile patients. In addition, secondary thickness has predictive value for clinical pregnancy.
... Following removal of duplicates and screening of titles and/or abstracts, 25 articles were considered eligible for full-text review. Ultimately, 17 studies were included in the systematic review and meta-analysis (Bu et al., 2019;Haas et al., 2019;Huang et al., 2020Huang et al., , 2021Ye et al., 2020;Zilberberg et al., 2020;Jin et al., 2021a,b;Kaye et al., 2021;Riestenberg et al., 2021;Yaprak et al., 2021;Gursu et al., 2022;Lam et al., 2022;Li et al., 2022;Olgan et al., 2022;Shah et al., 2022;Youngster et al., 2022). The process of study selection is detailed in Fig. 1. ...
... Thirteen cohorts were retrospective, and four were prospective, with the number of ET cycles varying between 71 and 4465. Thirteen studies focused on patients undergoing frozen embryo transfer (FET) (Bu et al., 2019;Haas et al., 2019;Huang et al., 2020;Ye et al., 2020;Zilberberg et al., 2020;Jin et al., 2021a,b;Kaye et al., 2021;Riestenberg et al., 2021;Yaprak et al., 2021;Olgan et al., 2022;Shah et al., 2022;Youngster et al., 2022), of which five included only euploid FET (Zilberberg et al., 2020;Jin et al., 2021a,b;Riestenberg et al., 2021;Shah et al., 2022). The other four studies focused on patients undergoing fresh ET (Huang et al., 2021;Gursu et al., 2022;Lam et al., 2022;Li et al., 2022), of which one included only oocyte donation (OD) cycles (Gursu et al., 2022). ...
... The other four studies focused on patients undergoing fresh ET (Huang et al., 2021;Gursu et al., 2022;Lam et al., 2022;Li et al., 2022), of which one included only oocyte donation (OD) cycles (Gursu et al., 2022). In FET and OD cohorts, eight used artificial cycles for endometrial preparation (Haas et al., 2019;Zilberberg et al., 2020;Jin et al., 2021a;Kaye et al., 2021;Riestenberg et al., 2021;Yaprak et al., 2021;Gursu et al., 2022;Olgan et al., 2022), three used natural cycles (Huang et al., 2020;Jin et al., 2021b;Youngster et al., 2022), and three used both (Bu et al., 2019;Ye et al., 2020;Shah et al., 2022). Among the cohorts using natural cycles, three used true natural cycles (Bu et al., 2019;Jin et al., 2021b;Youngster et al., 2022), while the other three used hCGtriggered modified natural cycles with or without letrozole (Huang et al., 2020;Ye et al., 2020;Shah et al., 2022). ...
STUDY QUESTION
Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes?
SUMMARY ANSWER
Endometrial compaction from the late-proliferative to secretory phase is not associated with live birth rate (LBR) and other pregnancy outcomes.
WHAT IS KNOWN ALREADY
Endometrial compaction has been suggested to be indicative of endometrial responsiveness to progesterone, and its association with ET outcome has been investigated but is controversial.
STUDY DESIGN, SIZE, DURATION
A systematic review with meta-analysis was carried out. PubMed, EMBASE, and Web of Science were searched to identify relevant studies from inception to 18 November 2022. The reference lists of included studies were also manually screened for any additional publications.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Cohort studies comparing ET pregnancy outcomes between patients with and without endometrial compaction were included. A review of the studies for inclusion, data extraction, and quality assessment was performed by two independent reviewers. The effect size was synthesized as odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity and publication bias were assessed by the I2 statistic and Egger’s test, respectively. The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate (MR), ongoing pregnancy rate (OPR), and ectopic pregnancy rate (EPR).
MAIN RESULTS AND THE ROLE OF CHANCE
Seventeen cohort studies involving 18 973 ET cycles fulfilled the eligibility criteria. The pooled results revealed that there were no significant differences between endometrial compaction and non-compaction groups in LBR (crude OR (cOR) = 0.95, 95% CI 0.87–1.04; I2 = 0%; adjusted OR (aOR) = 1.02, 95% CI 0.87–1.19, I2 = 79%), BPR (cOR = 0.93, 95% CI 0.81–1.06; I2 = 0%; aOR = 0.88, 95% CI 0.75–1.03, I2 = 0%), CPR (cOR = 0.98, 95% CI 0.81–1.18; I2 = 70%; aOR = 0.86, 95% CI 0.72–1.02, I2 = 13%), MR (cOR = 1.09, 95% CI 0.90–1.32; I2 = 0%; aOR = 0.91, 95% CI 0.64–1.31; I2 = 0%), and EPR (cOR = 0.70, 95% CI 0.31–1.61; I2 = 61%). The OPR was marginally higher in crude analysis (cOR = 1.48, 95% CI 1.01–2.16; I2 = 81%) among women with compacted endometrium, but was not evident in adjusted results (aOR = 1.36, 95% CI 0.86–2.14; I2 = 84%). Consistently, the pooled estimate of LBR remained comparable in further subgroup and sensitivity analyses according to the degree of compaction (0%, 5%, 10%, 15%, or 20%), type of ET (fresh, frozen, or euploid only), and endometrial preparation protocol (natural or artificial). No publication bias was observed based on Egger’s test.
LIMITATIONS, REASONS FOR CAUTION
Although the number of included studies is sufficient, data on certain measures, such as EPR, are limited. The inherent bias and residual confounding were also inevitable owing to the observational study design. Furthermore, inconsistent definitions of pregnancy outcomes may affect the accuracy of our pooled analysis.
WIDER IMPLICATIONS OF THE FINDINGS
Given the lack of prognostic value, assessing endometrial compaction or repeated EMT measurement on the day of ET may not be necessary or warranted.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by Natural Science Foundation of Jiangxi Province (20224BAB216025), National Natural Science Foundation of China (82260315), and Central Funds Guiding the Local Science and Technology Development (20221ZDG020071). The authors have no conflicts of interest to declare.
REGISTRATION NUMBER
CRD42022384539 (PROSPERO).
... Since multiple pregnancies are one of the major risk factors for miscarriage and premature birth, we do not have to transfer all the fresh embryos using this method, and the rest can be frozen for the future (4)(5)(6). Another reason for freezing is the insufficiency of the uterine endometrium in the ultrasound performed before the transfer of a new fetus (7). ...
Background: In vitro fertilization has advanced in many ways, and new techniques are challenging. Blastocyst transfer is an alternative method for embryo transfer (ET) to improve in vitro fertilization outcomes. Objective: The present study was performed to determine the effect of pregnancies resulting from ET in the blastocyst stage compared to the cleavage stage in frozen cycles to select a better method of assisted reproduction. Materials and Methods: This cross-sectional study was conducted on 194 women who referred to the Yazd Reproductive Sciences Institute, Yazd, Iran, between April 2019 and December 2020. They had a frozen ET as either cleavage or blastocyst (n = 97/each group). The study compared the pregnancy and fetal outcomes in the 2 groups of ET at the cleavage and blastocyst stages. Results: The results showed that the blastocyst stage group had higher levels of anti-Mullerian hormone, ovule number, 2 pronuclear number, and embryo number than the cleavage stage group. The frequency of chemical pregnancies was 52.6% and 36.1% in blastocyst and cleavage group respectively (p = 0.02). Also, the frequency of clinical pregnancies was 41.2% and 22.7% in blastocyst and cleavage group respectively (p < 0.001). No statistically significant difference was observed between 2 groups in abortion, preterm delivery, multiple births, preterm premature rupture of membranes, gestational diabetes and preeclampsia, ectopic pregnancy, neonatal hospitalization in Neonatal Intensive Care Unit, and fetal abnormalities (p > 0.05). Conclusion: The results showed that transmission in the blastocyst stage compared to the cleavage stage is associated with an increase in chemical and clinical pregnancy, while other pregnancy outcomes are the same in both groups. Key words: Blastocyst, Ovum cleavage stage, Embryo transfer.
... It has also been reported that increased progesterone concentrations increase the number and thickness of endometrial glands, leading to a higher pregnancy rate [24]. Another study showed that endometrial tissue cause "compaction" in thickness before and after decidualization occurs and this is expected to be a marker for predicting pregnancy rate; however, there are some negative reports regarding the prediction of pregnancy rate due to the change, and no conclusion has been reached as to whether or not, it is effective [25][26]. In this study, 3D endometrial tissues were cultured in four progesterone concentration groups and observed for desmoplasia. ...
Infertility in women is associated with various uterine and ovarian disorders. Treatment strategies for infertility can range from medications to embryo implantation through assisted reproductive technology (ART). ART has enabled considerable progress; however, there is currently no treatment to replace the endometrium itself. Decidualization requires a complex interaction between endometrial tissue and estrogen and progesterone. We aimed to create a three-dimensional endometrial-like tissue model using in-vitro cell sheet engineering with rat endometrium, and culture cells at different progesterone concentrations to mimic local concentrations. Histological and morphological changes revealed that development of the endometrial-like tissue was not proportional to progesterone concentrations in terms of thickness, number of endometrial glands, or area fraction of intimal glands. These results suggest that decidualization may not be commensurate with the local endometrial progesterone concentration. Notably, the number of endometrial glands increased in the high concentration group and compaction occurred, indicating that the endometrial conditions in the high concentration group may be most conducive to increase pregnancy rates. These findings suggest that there may be an “optimal progesterone concentration” for decidualization, application of which may lead to new strategies for improving pregnancy rates in women with infertility.
... Approximately half of women present reduced endometrial thickness around embryonic implantation relative to that measured in the estrogenic phase, a phenomenon known as endometrial compaction. In recent years, several studies have tried to determine if this event is a factor in reproductive outcomes (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Some authors have found no differences associated with endometrial compaction in Frozen embryo transfer (FET) during a replacement cycle with estroprogesterone therapy (22)(23)(24), whereas others have observed a positive association between compaction and pregnancy rates (25)(26)(27). ...
... Subsequently, a prospective investigation (30) analyzed euploid embryo transfers in replacement, stimulated, and natural cycles, finding no differences in endometrial compaction. Two studies have recently been carried out during natural cycles (31,32). In one (31), endometrial expansion was associated with a slight increase in clinical pregnancy, which was not reflected in changes in live births. ...
... In one (31), endometrial expansion was associated with a slight increase in clinical pregnancy, which was not reflected in changes in live births. However, a later study (32) reported that endometrial compaction was associated with a better pregnancy rate. ...
Introduction
Embryo implantation is a complex and poorly understood process. Most studies to date have focused on the analysis of the endometrium at the end of the estrogenic phase, while the available data on its importance after secretory transformation are limited and inconsistent. Current evidence does not allow for a conclusive interpretation of the changes observed in the pre-implantation endometrium, whether in the natural or replacement cycle, and their relevance in the development of a pregnancy or the implications for clinical practice.
Methods
Multicenter prospective observational cohort study. Based on our sample size calculation, the study group will consist of 206 women (exposed or “compaction” group: 103 women with a decrease of ≥ 5% in endometrial thickness between the estrogenic phase and the day of embryo transfer; non-exposed “non-compaction” group: 103 women with similar or greater endometrial thickness between these time points). The main objective of this study is to compare the ongoing pregnancy rates in natural cycles for euploid embryo transfer in patients who present endometrial compaction at the time of transfer versus those who with a stable or greater endometrial thickness with respect to the estrogenic phase. The estimated duration of the study is 30 months. Inclusion criteria are: 18 to 50 years of age, with primary or secondary infertility, subjected to endometrial preparation in a modified natural cycle for transfer of a genetically euploid blastocyst, from their own oocyte or oocyte donation, with a normal uterine cavity. Exclusion criteria are: uterine or endometrial disease (e.g., multiple myomatosis, severe adenomyosis, Asherman syndrome, refractory endometrium), conditions that prevent correct ultrasound assessment (tilted uterus), or a history of recurrent implantation failure or repeated miscarriages.
Discussion
The findings from this study will provide valuable insights into the potential influence of the “endometrial compaction” phenomenon on reproductive outcomes during natural cycle endometrial preparation. By examining this aspect, we aim to contribute to a better understanding of the factors that may impact successful outcomes in fertility treatments.
... Recently, a more dynamic approach to EMT has drawn interest, namely endometrial compaction (EC). EC is defined as the difference in EMT from the end of the follicular phase to the day of embryo transfer (ET) in fresh or natural frozen-thawed embryo transfer (FET) cycles [8,9]. For FET cycles prepared with artificial cycle protocol, EMT measurements are performed on the day before progesterone commencement and ET day [8]. ...
... The same significant relationship was observed for cut-off values of 10% and 15% as well [10]. Following those promising results, several studies on the predictive value of EC for live birth rates (LBR) or OPR presented conflicting results [8,9,[12][13][14][15]. At present, the predictive value of EC for LBR and OPR remains uncertain. ...
... A summary of the included studies is presented in Table 1. Of the studies included in the systematic review and meta-analysis, twelve were retrospective [10, 12-15, 17, 21-26] and four were prospective [8,9,27,28] in design. Notably, the study period of two studies performed in the same center had overlap for the period of two years [12,26]. ...
Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART.
MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy.
Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02; 10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24; 12 studies].
The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings.
PROSPERO CRD42023410389
... Two studies by the same group [139,140], who retrospectively analyzed embryo transfer images taken by abdominal ultrasonography (AUS) in HRT cycles, observed higher ongoing pregnancy rates in FET cycles that reported endometrial compaction of ≥ 5% compared with cycles in which the endometrium neither compacted nor expanded. This was supported by Youngster, M., et al. [141] in a retrospective observational study. However, several recent studies, including HRT cycles alone [142,143] or in combination with modified natural cycle (mNC) [144][145][146], failed to link endometrial compaction of ≥ 5% with pregnancy rates or live birth rates (LBRs). ...
Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a ‘back to nature’ approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled.
... These changes cause the luteal phase endometrium to appear hyperechoic and homogenous, which causes endometrial compaction. 17 We postulate that progesterone receptor resistance or deficiency in the endometrium would result in women with no change or an increase in endometrial thickness (ET) reflecting an insufficient progesterone impact. ...
... After ovulation, the progesterone level rises, endometrial proliferation stops, but the growth of glands and vessels continues (9). Follow-up natural cycle studies have shown that the endometrium, which reaches its peak before ovulation, plateaus or thins during the luteal phase (10). This compression/thinning of the endometrial thickness is described as endometrial compaction (EC) (11). ...
OBJECTIVE: Compression/thinning of the endometrial thickness with the effect of progesterone during the luteal phase of the menstrual cycle is defined as endometrial compaction. This study aimed to show the effect of changes in endometrial thickness in the luteal phase of intrauterine insemination cycles on pregnancy outcomes. STUDY DESIGN: Fifty-eight patients who were planned for intrauterine insemination were included in this prospective cohort study. The effect of the change between the patients' endometrial measurements on the day of trigger and the 7th day after intrauterine insemination on pregnancy outcomes were compared. Patients were divided into 3 groups according to endometrial thickness change. Those with an endometrial thickness change of less than 5% were called the no change group (n=18). The groups with endometrial thickness decreasing more than 5% (n=9) and increasing (n=31) formed the other two groups. In addition, the effect of luteal phase support on endometrial compaction was investigated. RESULTS: The highest pregnancy rate (55.6%) was observed in the group with more than 5% endometrial thinning. It was found to be 16.7% in the group without change and 19.4% in the group with an increased endometrial thickness (p=0.045). endometrial compaction and pregnancy rates were higher in the group given oral dydrogesterone for luteal support compared to those using vaginal micronized progesterone. CONCLUSION: Endometrial compaction increases clinical pregnancy in intrauterine insemination cycles. Further studies are necessary to confirm the results of this study.
Objective: There is no clear evidence of clinical significance of endometrial compaction, which can be measured by a reduction in endometrial thickness (EMT) during the follicular-luteal transition before the day of embryo transfer. In this study, we aim to determine whether endometrial compaction has an effect on in vitro fertilization (IVF) success.
Method (s): We searched PubMed, Cochrane, Embase, and Web of Science electronic databases for studies published in English up to March 2023. Heterogeneity between studies was assessed using the I2 statistic. The random effects model and fixed effects model was used to pool the risk ratio (RR) with a corresponding 95% confidence interval (CI). A subgroup analysis was performed based on different methods of ultrasonic measurement and different endometrial compaction rates (ECR). Stata 17.0 software was used for meta-analysis. Pregnancy outcomes, which included clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and spontaneous abortion rate, were evaluated.
Result (s): In this study, 18 cohort studies were included, involving 16,164 embryo transfer cycles. Pooled results indicated that there was no significant difference between the endometrial compaction group and the non-compaction group in terms of clinical pregnancy rate (RR [95% CI]=0.98 [0.90,1.08]; I2=69.76%), ongoing pregnancy rate (RR [95% CI]=1.18 [0.95,1.47]; I2 =78.77%), live birth rate (RR [95% CI]= 0.97 [0.92,1.02]; I2=0.00%) or spontaneous abortion rate (RR [95% CI]= 1.07[0.97,1.26]; I2=0.00%). According to the subgroup analysis of ultrasonic measurement methods, in the transvaginal ultrasound (TVUS) combined with abdominal ultrasonography (AUS) cycles of the endometrial compaction group, the rate of ongoing pregnancy (RR [95% CI] = 1.69 [1.26, 2.26]; I2 = 29.27%) and live birth (RR [95% CI] = 1.27 [1.00,1.61]; I2=62.28%) was significantly higher than that of the non-compaction group. Additionally, subgroup analysis based on ECR revealed a significantly higher rate of ongoing pregnancy when ECR ≥ 15% (RR [95% CI] = 1.99 [1.61, 2.47]; I2=0.00%).
Conclusion (s): Endometrial compaction has no adverse effect on clinical pregnancy rate, ongoing pregnancy rate, live birth rate, or spontaneous abortion rate. A possible explanation for the contradictory findings of previous studies lies in the method by which the EMT is measured.
Registration Number: CRD42023430511
