Effectiveness the perfusion of Endometrial and Subendometrial and Endometrial volume on the endometrial receptivity of FET Cycles

Objective: this study was effects of endometrial and subendometrial blood perfusion and endometrial volume on endometrial receptivity in frozen embryo transfer (FET) cycles. Materials and methods: This prospective observational cohort study, that on infertile women who referred for FET to Shariati Hospital and Omid Infertility Clinic in Tehran (Iran) .112 patients selected among eligible women with good quality embryos. After homogenization, participants underwent endometrial preparation for hormone replacement therapy (HRT) according to a similar routine protocol. On the day of the FET, they underwent a thorough ultrasound examination for possible effective parameters. Subsequently, one to two good quality blastocysts were transferred, and the pregnancy outcomes were monitored. Results: In vitro fertilization (IVF) was performed on 112 patients with a mean age of 33.93±4.93 years. Although, serum β-HCG level was used to confirm pregnancy. Accordingly, out of 112 participating patients, 50 (44.6%) became pregnant after IVF. Based on the results of this study, the endometrial blood flow was significantly different between the two groups of pregnant and non-pregnant women, so that a higher pregnancy rate was observed in participants with multi-focal and spare endometrial blood flows (P<0.05). Additionally, a significant relationship between endometrial blood flow and pregnancy outcome so that there was more ongoing pregnancy rates in those with multi-focal and spare endometrial blood flows (P<0.05). But the endometrial variables of volume, length, width, thickness and pattern were not significantly different between the two groups of pregnant and non-pregnant women. Moreover, contextual parameters had no significant relationship with pregnancy outcome (P>0.05). Endometrial measurement indices were also ineffective on pregnancy outcomes and no significant difference was there between the groups (P>0.05). Conclusion: Collectively, the endometrial blood flow can play an effective role in improving pregnancy event and its stability after IVF, but the endometrial volume was unable to predict pregnancy event and its stability after IVF.

O-031 Importance of blood flow to human implantation

text The success of embryo implantation depends on a plethora of factors, with embryo quality and endometrial receptivity belonging to the most important ones. The receptive phenotype of endometrium develops in reaction to appropriate estrogen stimulation in the proliferative phase and embryo-synchronized maturation warranted by the action of progesterone. Uterine blood supply, myometrial contractions and the activity of local immune cells also belong to important factors affecting the outcome of both natural and assisted reproduction. Endometrial perfusion was shown to be an independent receptivity parameter, showing a direct association with pregnancy outcomes. Historically, the use of Doppler parameters of uterine vessels was studied as a reflection of blood flow to the endometrium. Although some authors showed a correlation between blood flow in uterine arteries and success rates in IVF cycles, it might not reflect the actual endometrial flow as most of the blood volume goes through myometrium, not endometrium. Currently, using available ultrasound tools – 2D/3D Power Doppler with VOCAL (Virtual Organ Computer-Aided Analysis) software enables clinicians to evaluate parameters of endometrial perfusion in a matter of minutes. In this method, ultrasound system can calculate indices reflecting endometrial blood flow - vascularity index (VI), endometrial flow index (FI), and endometrial vascularity flow index (VFI) which are based on the total and relative amounts of Power Doppler signal (corresponding to the blood flow) within the volume of interest. Endometrial blood flow parameters can be altered in implantation limiting conditions such as endometriosis or chronic intrauterine inflammation. It was also shown to be influenced by implantation-related hormones such as oxytocin. Oxytocin receptor antagonists were shown to decrease uterine contractions in non-pregnant uteri of women being prepared for embryo transfer procedure. This class of medications has been extensively studied as potential candidates for medications promoting embryo implantation in IVF-ET treatments. In several studies, it was shown that mixed oxytocin/vasopressin V1A receptor antagonist atosiban, which is currently registered in Europe for the tocolysis in preterm labour, had the potential of improving implantation rates. Interestingly, this effect was confirmed also in women without pronounced contractions. Additionally, it has been demonstrated that oxytocin antagonism enhances endometrial decidualization and influences other parameters necessary for the acquisition of the endometrial receptivity phenotype. Considering that atosiban and other oxytocin antagonists relax uterine blood vessels and increase endometrial blood flow, it was hypothesized that improvement in endometrial perfusion could be an additional mechanism for observed support of embryo implantation. A similar finding was confirmed in our study on nolasiban – a non-peptide, orally active, oxytocin receptor-specific antagonist. In the 1st phase study on volunteers undergoing estrogen/progesterone endometrial preparation reflecting the synchronization for embryo transfer, it was confirmed that application of nolasiban decreased uterine contractions and improved FI and VFI parameters of endometrial perfusion. Such an effect lasted for more than 24 hours after dosing. The study results suggested that oxytocin antagonism could have an effect on endometrial perfusion, and its potential clinical significance requires further investigation. In a longer perspective, once confirmed it would mean that, apart from the possibility of observation of endometrial blood flow, we could have a tool for improving it, which would hopefully lead to improved outcomes of assisted reproduction treatments.

Alterations of Uterine Blood Flow During the Follicular Phase in Patients With Recurrent Implantation Failure: A Doppler Ultrasonographic Study

Objectives: The dynamics of blood flow in the endometrium plays a crucial role during the implantation process. This study aimed to assess the uterine perfusion during the follicular phase in patients with a history of recurrent implantation failure (RIF) and healthy fertile women using the transvaginal ultrasound color Doppler method. Materials and Methods: To this end, 50 patients with RIF and 50 age-matched healthy fertile women were recruited in this case-control study. The transvaginal color Doppler ultrasonography was used to evaluate the pulsatility index (PI) and resistance index (RI) of the uterine, arcuate, and sub-endometrial arteries during the follicular phase in both groups. Results: The RI and PI of both right and left uterine arteries were higher in the RIF group compared to the fertile women (P<0.05). Our results showed that the PI and RI of sub-endometrial blood flow and the RI of arcuate arteries were substantially higher in the group with a history of RIF in comparison with the control group. However, the PI of arcuate arteries was not significantly different between the groups. Conclusions: Adequate uterine perfusion and sub-endometrial blood flow are necessary to achieve successful implantation and pregnancy since our results demonstrated the higher resistance of uterine and sub-endometrial arteries in patients with a history of RIF. Thus, the assessments of uterine perfusion indices during the follicular phase could be used as a non-invasive method in the evaluation of patients with RIF.

Effect of nitric oxide donors on uterine and sub-endometrial blood flow in patients with unexplained infertility: a randomized controlled trial

Background: Impaired sub-endometrial perfusion might reduce endometrial receptivity and possibly contribute to unexplained infertility. A favorable effect on sub-endometrial blood flow has been demonstrated with nitric oxide.Methods: This randomized controlled trial evaluated the effect of nitroglycerine on uterine and sub-endometrial blood flow in women with unexplained infertility. Sixty women were randomized into 2 equal groups. The study group received 5mg nitroglycerine patch daily from day 2 of the cycle till the evaluation day and the control group received no treatment. Independent of the study arms, 30 parous women were included as the fertile group. Six to eight days after detecting luteinizing hormone surge, women were assessed for endometrial thickness, uterine artery blood flow with color Doppler and sub-endometrial blood flow with three-dimensional power Doppler.Results: Compared to fertile women, cases with unexplained infertility (control group) had a significantly thinner endometrium, higher uterine artery Doppler indices and lower sub-endometrial blood flow. Women who received nitroglycerin showed a significant improvement in sub-endometrial blood flow while uterine artery blood flow did not show a significant difference; however, the values were also comparable to fertile women. In addition, no effect on endometrial thickness was found with nitroglycerin treatment. Nitroglycerin treatment side effects were headache, blurring of vision and hypotension. These adverse effects were not significant compared to controls.Conclusions: In women with unexplained infertility, nitroglycerin significantly improved the sub-endometrial blood flow but did not affect the endometrial thickness.