Two-Dimensional and Three-Dimensional Doppler in Reproductive Medicine

Fig. 3.1

Right (a) and left (b) uterine blood flow measured by 2D Doppler ultrasound

Flow velocity waveforms are obtained from the ascending main branch of the uterine artery on the right and left side of the cervix in a longitudinal plane before it enters the uterus. The ‘gate’ of the Doppler is positioned when the vessel with good colour signals is identified on the screen. The PI and RI of the uterine arteries were calculated electronically when three similar, consecutive waveforms of good quality were obtained.

Good uterine blood flow as shown by low PI or RI is correlated with successful IVF outcomes [12, 13]. Steer et al. [12] classified PI measured on the day of ET as low, medium and high in the ranges of 0–1.99, 2.00–2.99 and ≥3.00, respectively, and reported a 35 % implantation failure when PI was >3.0. Using a PI upper limit of 3.0 [12] or 3.3 [13], the uterine Doppler flow indices have a high negative predictive value and sensitivity (in the ranges of 88–100 % and 96–100 %, respectively) and a relatively higher range of positive predictive value and specificity (44–56 % and 13–35 %, respectively) when compared with endometrial thickness and pattern [5].

Uterine artery Doppler study may not reflect the actual blood flow to the endometrium as the major compartment of the uterus is the myometrium and there is collateral circulation between uterine and ovarian vessels. I have shown 2D Doppler study of uterine vessels is a poor reflection of subendometrial blood flow by 3D power Doppler in both stimulated and natural cycles as endometrial and subendometrial 3D Doppler flow indices were similar among patients with averaged uterine PI <2.0, 2.0–2.99 and ≥3.0. [14].

Endometrial and Subendometrial Blood Flow by 2D Doppler

Endometrial and subendometrial blood flow examined by colour (Table 3.1) and power Doppler (Table 3.2) was correlated with implantation or pregnancy rates during IVF treatment. 2D Doppler flow indices of spiral arteries such as PI and PSV are not predictive of pregnancy [8, 19, 22], although Battaglia et al. [16] and Kupesic et al. [23] found significantly lower spiral artery PI in pregnant cycles than nonpregnant cycles.

Table 3.1

Summary of studies of endometrial blood flow by 2D colour Doppler

Study	IVF cycles	USS parameters	USS day	Results
Popovic-Todorovic et al. [15]	96 cycles using a long protocol	Spiral PI and PSV	hCG	No difference in subendometrial PI and PSV between pregnant and nonpregnant cycles
Popovic-Todorovic et al. [15]	96 cycles using a long protocol	Presence of endometrial and subendometrial flow	hCG	Absent subendometrial flow associated with no pregnancy
Battaglia et al. [16]	60 cycles	Uterine and spiral PI	OR	Uterine and spiral PI lower in pregnant than nonpregnant cycles
Battaglia et al. [16]	60 cycles	Presence of endometrial blood flow	OR	Absent subendometrial flow associated with no pregnancy
Chien et al. [17]	623 cycles using ultrashort and ultralong protocols	Uterine and spiral PI and RI	ET	Significantly lower implantation and pregnancy rates in patients without endometrial/subendometrial flow
Chien et al. [17]	623 cycles using ultrashort and ultralong protocols	Presence of endometrial and subendometrial (<10 mm) blood flow	ET	Presence of subendometrial flow 5.9 times to become pregnant than those with absent flow

USS ultrasound, PI pulsatility index, PSV peak systolic velocity, OR oocyte retrieval, ET embryo transfer

Table 3.2

Summary of studies of endometrial blood flow by 2D power Doppler

Study	IVF cycles	USS parameter	USS day	Results
Yang et al. [18]	95 cycles using long and short protocols	Intraendometrial power Doppler area (EDPA) <5 mm²; ≥5 mm²	OR	Higher EDPA in pregnant cycles
Yang et al. [18]	Endometrium ≥10 mm	Intraendometrial power Doppler area (EDPA) <5 mm²; ≥5 mm²	OR	Lower implantation and pregnancy rates when EDPA <5 mm²
Yuval et al. [19]	156 cycles using a long protocol	PI and RI	OR and ET	No difference in any USS parameters between pregnant and nonpregnant cycles
Contart et al. [20]	185 cycles using a long protocol	Fundal region along transverse plan; grades I, II, III and IV according to visualisation of power Doppler in the quadrants	hCG	Implantation and pregnancy rates similar in all grades of endometrial vascularity
Schild et al. [8]	135 cycles using a long protocol; first cycle only	PI and PSV of vessels in endometrium and subendometrial area (<5 mm)	OR	No difference in spiral artery PI and PSV between pregnant and nonpregnant cycles
Schild et al. [8]	135 cycles using a long protocol; first cycle only		OR	Non-detectable spiral blood flow was not associated with a lower implantation rate
Maugey-Laulon et al. [21]	144 cycles using a long protocol	Presence of endometrial and subendometrial blood flow	ET	Absent endometrial and subendometrial flow associated with a lower pregnancy rate

USS ultrasound, PI pulsatility index, PSV peak systolic velocity, OR oocyte retrieval, ET embryo transfer

Yang et al. [18] used a computer software to measure the area and intensity of colour signals present in the endometrium in a longitudinal axis, i.e. intraendometrial power Doppler area (EDPA). Significantly higher EDPA was found in pregnant cycles than nonpregnant cycles (8.8 mm² vs. 5.8 mm² respectively). Patients with EDPA <5 mm² had significantly lower pregnancy rate (23.5 % vs. 47.5 %; P = 0.021) and implantation rate (8.1 % vs. 20.2 %; P = 0.003) than those with ≥5 mm². Contart et al. [20] graded endometrial blood flow by the visualisation of power Doppler in the quadrants in the fundal region of the transverse plane but could not demonstrate any predictive value of such grading system.

Presence of endometrial and subendometrial blood flow can be identified easily in 2D Doppler ultrasound. Absent endometrial and subendometrial blood flow has been shown to be associated with no pregnancy [16, 22] or a significantly lower pregnancy rate [17, 21].

Endometrial and Subendometrial Blood Flow by 3D Doppler

3D power Doppler ultrasound with the aid of the VOCAL® (Virtual Organ Computer-Aided Analysis) imaging program for the 3D power Doppler histogram can be used to measure the endometrial volume and indices of blood flow within the endometrium (Fig. 3.2). Vascularisation index (VI), which measures the ratio of the number of colour voxels to the number of all the voxels, is thought to represent the presence of blood vessels (vascularity) in the endometrium, and this was expressed as a percentage (%) of the endometrial volume. Flow index (FI), the mean power Doppler signal intensity inside the endometrium, is thought to express the average intensity of flow. Vascularisation flow index (VFI) is a combination of vascularity and flow intensity [24].

Fig. 3.2

Endometrial volume (a) and blood flow (b) measured by 3D Doppler ultrasound

The subendometrium can be examined through the application of ‘shell imaging’ which allows the user to generate a variable contour that parallels the originally defined surface contour. The VI, FI and VFI of the subendometrial region are obtained accordingly (Fig. 3.3). The intra-observer reliability and interobserver reliability of endometrial and subendometrial blood flow by 3D power Doppler have been confirmed to be high with all measurements obtaining an intra-class correlation of above 0.9 [25, 26].

Fig. 3.3

Subendometrial volume (a) and blood flow (b) measured by 3D Doppler ultrasound

Studies addressing the role of endometrial and subendometrial blood flow measured by 3D Doppler in IVF treatment are summarised in Table 3.3. Schild et al. [27] measured the subendometrial blood flow after pituitary downregulation but prior to ovarian stimulation and showed that subendometrial VI, FI and VFI were significantly lower in pregnant cycles than nonpregnant ones. Logistic regression analysis found that the subendometrial FI was the strongest predictive factor for the pregnancy outcome among other 3D Doppler flow indices.

Table 3.3

Summary of studies of endometrial and subendometrial blood flow by 3D power Doppler ultrasound

Study	IVF cycles	Inclusion/exclusion criteria	USS day	Results
Schild et al. [27]	75 cycles using a long protocol	Inclusion criteria	Before stimulation	Subendometrial VI, FI and VFI lower in pregnant than nonpregnant cycles
Schild et al. [27]	ET 2 days after TUGOR	Downregulation confirmed (endometrium <5 mm, no ovarian cyst of >2.5 cm, serum oestradiol <60 pg/mL)	Before stimulation	Subendometrial FI is the strongest predictive factor for IVF in logistic regression analysis
Kupesic et al. [23]	89 cycles using a long protocol	Inclusion criteria	ET (hCG +7)	Higher subendometrial FI in pregnant cycles
	Blastocyst transfer 5 days after TUGOR	Serum FSH < 10 IU/L
	Blastocyst transfer 5 days after TUGOR	No fibroid, ovarian cysts and ovarian endometriosis
Wu et al. [28]	54 cycles; first cycle only (details of ovarian stimulation and ET not given)	Inclusion criteria	hCG	Subendometrial VFI higher in pregnant cycles
		Age <38 years
		Normal uterine cavity
		Serum FSH <15 IU/L
		≥2 good quality embryos
Dorn et al. [29]	42 cycles using a long protocol	Exclusion criteria	OR	No difference in subendometrial VI, FI and VFI between pregnant and nonpregnant cycles
		Polycystic ovary syndrome
		Endometrium <6 mm
		Gynaecological surgery
Järvelä et al. [30]	35 cycles using a long protocol	Exclusion criteria	After stimulation and OR	No difference in endometrial and subendometrial VI between pregnant and nonpregnant cycles on both days
	ET 2 days after TUGOR	Uterine fibroids
		Endometriosis
		Single ovary
		Previous operation on uterus or salpingectomy
Ng et al. [31]	451 cycles using a long protocol; first cycle only	Inclusion criteria	OR	Endometrial VI and VFI lower in pregnant cycles
Ng et al. [31]	ET 2 days after TUGOR	Normal uterine cavity on scanning	OR	Endometrial VI and VFI lower in pregnant cycles
Ng et al. [32]	193 cycles	Inclusion criteria	LH + 1	No difference in endometrial and subendometrial 3D Doppler flow indices between pregnant and nonpregnant cycles
Ng et al. [32]	Frozen-thawed embryo transfer cycles	Normal uterine cavity	LH + 1
Mercè et al. [33]	80 cycles using a long protocol	Inclusion criteria	hCG	Higher endometrial VI, FI and VFI in pregnant cycles
		First cycle
		Normal uterine cavity
		Serum FSH <10 IU/L
		Regular cycles
		Non-smokers
Ng et al. [34]	293 cycles using a long protocol	Inclusion criteria	OR and ET	No difference in endometrial and subendometrial 3D Doppler flow indices on the 2 days and changes in these indices between pregnant and nonpregnant cycles
	ET 2 days after OR	First cycle
	ET 2 days after OR	Normal uterine cavity