Current methods of ER assessment based on morphology, molecular biology, proteomics, and gene chips are generally invasive, time-consuming, and require assessment 1 menstrual cycle in advance, which does not allow for timely pregnancy guidance for transplantation cycles. Noninvasive methods and indicators for endometrial receptivity assessment have become a pressing need in assisted reproductive medicine. Ultrasound assessment has the advantage of being clinically noninvasive, easy and timely, and highly operable, and is considered to have a potential role in the assessment of ER[15]. With the development of ultrasound technology, especially the use of 3D ultrasound and Doppler has provided a simple, noninvasive and reproducible method for clinical assessment of endometrial tolerability. More and more ultrasound indices are being used to visualize the endometrium and to try to find indices with predictive value for ER, and many different studies have emerged. Previous studies have mostly focused on the effect of ER on pregnancy outcome for IVF-ET or IUI and have not excluded the effect of embryo on pregnancy outcome. The present study focuses on the assessment of ER before transfer in patients undergoing PGD/PGS transfer, excluding the effect of embryonic factors on pregnancy outcome and focusing on the effect of ER on pregnancy outcome. Our study is more focused and innovative compared to other studies.
Endometrial thickness (EMT) is one of the commonly used indicators for ultrasound evaluation of endometrial receptivity, but its predictive value for embryo transfer success has been inconsistently stated in previous studies. Some authors suggest that clinical pregnancy rates in IVF-ET are positively correlated with EMT, and that as endometrial thickness increases, patients have higher pregnancy and implantation rates, lower spontaneous abortion rates, and higher live birth rates. Numerous studies have shown that an excessively thin uterus does not facilitate embryo implantation, leading to difficulties in conception. Patients with an EMT ≤7 mm or <8 mm on HCG trigger day have a decreased clinical pregnancy rate, a spontaneous abortion rate of more than 50%, and a significantly lower live birth rate[18, 19]. Some studies have also found no correlation between endometrial thickness and pregnancy rates. For example, weissman et al. found a decrease in both pregnancy and implantation rates after the endometrium exceeded 14 mm [20, 21]. It has also been studied that there is no correlation between EMT and pregnancy rate[22], but suggests that the minimum value of EMT required for pregnancy is 6.9 mm[23]. It is controversial whether EMT alone can be used as a predictor of pregnancy outcome[24]. In our study it was concluded that EMT correlated with pregnancy, with patients in the pregnant group having higher EMT than in the non-pregnant group. The inclusion of EMT in the multifactorial regression analysis resulted in an OR=4.815, 95% CI: 1.381 to 16.788, and the inclusion of ROC analysis showed an area under the curve of 0.812 (95% CI: 0.756 to 0.869), demonstrating that EMT can be used as an independent factor to predict pregnancy outcome in PGD/PGS transplantation cycles.
A good endometrial blood supply is necessary for embryo implantation, and ultrasound detection of endometrial blood flow can directly reflect the microenvironment of the embryo implantation site and has an important predictive value for endometrial receptivity. It has been suggested that endometrial blood flow abundance is strongly associated with successful pregnancy during ovulation-assisted cycles[25], and the clinical pregnancy rate was significantly higher in the group with detectable blood flow in both the endometrium and subendometrium on HCG day than in the group with no detectable blood flow[26, 27]. In this study, we found that the pregnancy rate of patients gradually increased with the increase of endometrial blood flow abundance. The number of endometrial blood flow branches was higher in the pregnant group than in the non-pregnant group, and after including this index in the multifactorial regression analysis and ROC analysis, the results showed that the number of endometrial blood flow branches had some predictive value as an independent factor for PGD/PGS pregnancy outcome. The proportion of type II+III blood flow was higher in the pregnancy group than in the non-pregnancy group. The area under the curve was found to be 0.567 ( 95% CI: 0.498-0.637) when endometrial blood flow typing was included in ROC analysis, respectively, which can be used to predict clinical pregnancy outcome in PGD/PGS embryo transfer, but its use alone has low accuracy in predicting clinical pregnancy rate. However, the endometrial 3D ultrasound blood flow parameters VI, FI, VFI, PI, RI, and S/D were not statistically significant; these parameters probe the overall vascularity and density of blood flow in the endometrium, and based on the presence of endometrial disruption in the selected cases in patients with lesions such as uterine adhesions, uterine polyps, and submucosal myomas, where patients still had pregnancy, it can be speculated that embryo implantation may be influenced by the blood supply to the endometrium at the local implantation site. It can be assumed that embryo implantation may be more influenced by the blood supply to the endometrium at the local implantation site rather than the overall blood supply to the endometrium. Because this study is a pre-PGD/PGS transfer ultrasound endometrial receptivity data, compared to IVF/ICSI transfer there are higher requirements in terms of endometrial receptivity in terms of blood flow, the transfer was cancelled when endometrial blood flow typing did not reach type II or III, and the number of endometrial blood flow branches was too low, and the endometrium was readjusted and then prepared for transfer again, resulting in some bias in the data. The effect of ultrasound flow parameters on pregnancy outcome in PGD/PGS transplantation needs to be further investigated by collecting more samples.
Pregnancy outcome in IVF-ET patients can be affected by a combination of multiple components and factors, including age, basal endocrine levels, etc. FSH is a gonadotropin, and insufficient FSH secretion during the follicular phase results in delayed development of the endometrium during the luteal phase, which is detrimental to embryo implantation. In this study, basal FSH results were lower in the pregnancy group than in the non-pregnancy group, and after considering this factor as an influential factor in pregnancy outcome in PGD/PGS patients, basal FSH was included in the multifactorial regression analysis and ROC analysis, and the results showed that basal FSH did not independently predict pregnancy outcome in PGD/PGS. In contrast to the results of previous studies, basal FSH was considered to affect ovarian reserve function, although to some extent, but mostly related to indirect effects[28]. One study found that the correlation between FSH/LH ratio and ovarian reserve function was more pronounced compared to FSH alone[29]. It has also been shown that basal FSH has little predictive value for ovarian responsiveness and continued pregnancy in IVF cycles, and is only significant in some patients with higher basal FSH (15 mIU/mL) [30].
In current studies using ultrasound for ER assessment, it is basically assumed that the timing of the graft window is fixed for different menstrual cycles of the patient, but this is not the case, and the timing of the graft window varies in different menstrual cycles. Therefore, finding a method of ER assessment based on individualization may be the direction of ER assessment studies. The study reports that an endometrial receptivity array (ERA) has been developed to predict ER and to personalize the optimal date for embryo transfer. The study is looking for a fast, accurate and less invasive clinical tool for personalized embryo transfer guidance[29, 31]. Hashimoto et al. [32]found the importance of using ERA to find individualized implantation windows by performing ERA testing in 50 patients with repeated transfer failures.
In conclusion, endometrial thickness, endometrial blood flow branch count, endometrial blood flow typing, and basal FSH have different degrees of influence on pregnancy outcome in PGD/PGS patients, and endometrial thickness can be used as an independent factor to influence pregnancy outcome. In FET cycles, ultrasound may play a unique role in real-time localization of embryo implantation and endometrial blood flow detection, and combining the advantages of ultrasound, ERA, and modern molecular techniques will allow for more accurate assessment of ER and improved pregnancy rates in FET.