The uterine endometrium shows multiple growth phases during menstrual cycle. By the end of previous menstruation, endometrial proliferation starts during follicular phase of menstrual cycle. The endometrium continues to grow and changes from proliferative phase to secretory phase during the luteal phase of menstrual cycle. The endometrium continues to grow until sudden drop in the hormone level occur leading to menstruation [11].
The main function of endometrium is to provide a time-limited support for embryo implantation. The uterine endometrium shows resistance for embryo implantation during most phases of menstrual cycle. Endometrium achieves special receptive properties during luteal phase of menstrual cycle and this period is called implantation window [12].
The blood flow impedance of uterine and spiral arteries is changed periodically during normal menstrual cycle. The lowest blood flow impedance occurs during the mid-luteal phase of menstrual cycle. The high uterine blood flow in this stage increases the endometrial receptivity and gives a good chance for embryo implantation to occur [13].
Many methods are used to evaluate the receptivity of the endometrium like endometrial biopsy and immune-histochemical analysis. Doppler ultrasonography is considered as simple non-invasive method that could be used to assess the blood flow impedance of uterine arteries and provides an indirect method to measure the receptivity of the endometrium [7].
In women with unexplained infertility, the perfusion of the endometrium in the pre-implantation stage is lower than normal despite of endometrial measurement or hormonal profile [14].
Many studies showed that in women with unexplained infertility the uterine and spiral arteries’ impedance was higher than that of the fertile females and the decrease of the perfusion of uterus may be a cause of the unexplained infertility [8, 11, 13].
Many studies evaluated the role of subendometrial blood flow impedance in the pathogenesis of unexplained infertility. In these studies, transvaginal uterine artery Doppler indices were measured in the mid-luteal phase of menstrual cycle (pre-implantation phase) in women diagnosed with unexplained infertility and compared the values with that of control fertile groups. The studies reported that in women with unexplained infertility, the pulsitility index (PI) and resistance index (RI) of uterine artery were increased significantly in women diagnosed with unexplained infertility more than fertile women [8, 13,14,15,16,17].
The most common Doppler indices used for assessment of uterine artery blood flow impedance are the resistance index (RI), the pulsatility index (PI), and the systolic/diastolic (S/D) ratio [18].
This study included two groups of women. Group 1 (study group) included 40 women diagnosed with unexplained infertility (Figs. 6, 7, 8, 9, and 10) and group 2 (control group) included 30 fertile women who visited the radiology clinic seeking for transvaginal ultrasound for any other gynecological cause (Figs. 4 and 5).
In this study, the mean age of the study group was 26.9 ± 3.8 years and the mean age of the control group was 28.5 ± 4.9 years with no significant difference between both groups (P = 0.194) as regards the age. These results were matched with Hashad et al.; they concluded that the mean age of women in the study group was 26 years while in the control group was 27 years [8]. El-Shourbagy et al. concluded that as regards the age there was no significant difference between fertile and infertile groups [3].
In this study, the resistance index (RI) mean value was 0.9 ± 0.06 SD in the study (infertile) group and was 0.6 ± 0.04 SD in the control (fertile) group with statistically significant difference between both study and control groups. These results were matched with Hashad et al. they concluded that the mean RI values in the infertile group and the fertile group were 0.69 and 0.61 respectively and that there was a significant difference between the fertile and infertile groups as regards the mean value of resistance index (RI) [8].
In the current study, the mean value of pulsatility index (PI) in the study (infertile) group was 2.9 ± 0.7 SD and was 1.5 ± 0.4 SD in the control (fertile) group with statistically significant difference between both groups. These results were matched with Hashad et al. [8] and Selda et al. [15]; they concluded that there was a significant difference between the fertile and infertile groups as regards the mean value of pulsatility index (PI). Hashad et al. found that the mean values of PI in the study and control groups were 1.3 and 1.16 respectively. Selda et al. found that the mean values of PI in the study and control groups were 0.8 and 0.7 respectively [15].
This study was in agreement with Chien et al.; they concluded that resistance index (RI) and pulsatility index (PI) of uterine artery were lower in conception menstrual cycles more than in non-conception cycles [19].
Studies of Devyatova et al. found that 35% of females who underwent in vitro fertilization (IVF) with mean pulsatility index (PI) of uterine artery more than 3 failed to conceive [9].
The study of Cacciatore et al. aimed to detect the role of uterine artery blood flow impedance in the outcome of in vitro fertilization embryo transfer (IVF-ET) by measuring uterine artery RI and PI values. Their results were in agreement with our results as they concluded that the uterine artery blood flow impedance was significantly lower in the conception group than in non-conception group. They also concluded that the endometrium was not receptive and implantation did not occur when resistance index (RI) and pulsatility index (PI) of uterine arteries are more than 0.72 and 1.6 respectively [20].
In this study, the mean uterine artery systolic/diastolic (S/D) ratio for the study (infertile) group was found to be 8.0 ± 3.4 SD and for the control (fertile) group was 2.7 ± 0.3 SD. The difference between the study and the control group as regards systolic/diastolic (S/D) ratio was statistically significant.
The study of Ari et al. was done by using 3D power Doppler ultrasound to assess the blood flow of endometrium in order to predict the pregnancy outcome after intrauterine insemination (IUI) [21]. Ari et al. concluded that the Doppler indices measured by 3D power Doppler like resistance index (RI), pulsatility index (PI), and systolic/diastolic (S/D) ratio were useful predictors for pregnancy after IUI [21].
Khan et al. reported that pregnancy did not occur in the case of absent or reversed uterine end diastolic blood flow [22].
In the current study, the mean endometrial thickness of the study group was 10.4 mm ± 2.4 SD and of the control group was 12.1 mm ± 1.8 SD. The difference between the study and the control group as regards endometrial thickness was statistically significant between both groups. This matched with the studies of Khan et al. [22], Noyes et al. [23], and Kovacs et al. [24] they reported that pregnancy rates were significantly higher in women with endometrial thickness more than 7 mm and no pregnancy was reported when endometrial thickness was lower than 7 mm.
In this study, the best cut-off value of resistance index (RI) for predicting increased uterine blood flow impedance was RI more than 0.67, with sensitivity of 100%, specificity of 96.7%, positive predictive value of 97.5%, negative predictive value of 100%, and diagnostic accuracy of 98.6%.
In the current study, the best cut-off value of pulsatility index (PI) for predicting increased uterine blood flow impedance was PI more than 1.95, with sensitivity of 95%, specificity of 86.7%, positive predictive value of 90.47%, negative predictive value of 92.86%, and diagnostic accuracy of 91.42%.
In this study, the best cut-off value of systolic/diastolic (S/D) ratio for predicting increased uterine blood flow impedance was S/D ratio more than 3, with sensitivity of 100%, specificity of 96.7%, positive predictive value of 97.56%, negative predictive value of 100%, and diagnostic accuracy of 98.57%.
The current study results were in agreement with Hashad et al.’s study; they reported that best cut-off value of resistance index (RI) and pulsatility index (PI) for predicting increased uterine blood flow impedance was more than 0.67 and 1.37 respectively with sensitivity of both RI and PI being 70% and 77.5 respectively, specificity of both RI and PI 75% and 85% respectively, positive predictive value of both RI and PI 85% and 87% respectively, negative predictive value of both RI and PI 60% and 66% respectively, and diagnostic accuracy of both RI and PI 69.7% and 85.3 respectively [8].
This study concluded that the mean values of uterine artery Doppler indices including the resistance index (RI), the pulsatility index (PI), and the systolic/diastolic (S/D) ratio were significantly higher in the study (infertile) group than the control (fertile) group with significant difference in the endometrial blood flow impedance and uterine perfusion in both study and control groups.
Uterine artery Doppler with measurement of Doppler indices including the resistance index (RI), the pulsatility index (PI), and the systolic/diastolic (S/D) ratio provides high sensitivity and specificity with high diagnostic accuracy for diagnosis of high uterine artery blood flow impedance in women diagnosed with unexplained infertility.
This study concluded that the uterine blood flow impedance was significantly higher in women that were diagnosed with unexplained infertility (study group) more than fertile women (control group), so high uterine blood flow impedance and low endometrial perfusion diagnosed by uterine artery Doppler may contribute in the etiology of unexplained infertility.
This study is recommended to include the uterine artery Doppler in the investigations of unexplained infertility.
This study is recommended to study a large numbers of female diagnosed with unexplained infertility and study the effect of drugs that increase uterine perfusion for treatment of unexplained infertility and increase the possibility of pregnancy.