REVIEW ARTICLE


https://doi.org/10.5005/jp-journals-10009-1949
Donald School Journal of Ultrasound in Obstetrics and Gynecology
Volume 16 | Issue 4 | Year 2022

Volume Ultrasound in Infertility


Sonal Panchal

Department of Ultrasound, Dr. Nagori’s Institute for Infertility and IVF, Ahmedabad, Gujarat, India

Corresponding Author: Sonal Panchal, Department of Ultrasound, Dr. Nagori’s Institute for Infertility and IVF, Ahmedabad, Gujarat, India, e-mail: sonalyogesh@yahoo.com

Received on: 05 October 2022; Accepted on: 16 October 2022; Published on: 26 December 2022

ABSTRACT

Introduction: Volume ultrasound (US) is an important complementary addition to the brightness (B) mode and Doppler transvaginal assessment of the reproductive organs in patients presenting with fertility problems. It has an important role in pretreatment assessment and also the monitoring of the treatment cycles and decision-making on the treatment protocols.

Discussion points: Three-dimensional (3D) US is a modality of choice for differential diagnosis of Mullerian abnormalities. When used with Doppler and saline infusion sonohysterography (SIS), 3D US may almost eliminate the need for diagnostic hysteroscopy. It can be used to confidently diagnose polyps, hyperplasia, synechiae, chronic endometritis (CE), etc., all endometrial pathologies. A 3D US is considered a modality, at par with magnetic resonance imaging (MRI), for the assessment of endometrio-myometrial junction and so for the diagnosis of adenomyosis. It also enables the documentation of endometrial invasion in adenomyosis. In cases with submucosal fibroids, it is the 3D US that allows a clear assessment of the extent of endometrial invasion or distortion. The 3D US also has a role in uterine scar and cervical assessment. A 3D hystero-salpingo contrast sonography (HyCoSy) is an excellent modality for the assessment of tubal patency. Virtual organ computer-aided analysis (VOCAL) and sonography-based automated volume count (SonoAVC) are volume calculation software and are very useful for the assessment of ovarian volume, stromal volume, follicular, and endometrial volume, and for the accurate calculation of antral follicle count (AFC). When combined with power, Doppler can give a precise assessment of the global vascularity of these structures that can be all used to improve the assisted reproductive technology (ART) results. A 3D US can also be used to predict and diagnose the complications of ART, like ovarian hyperstimulation syndrome (OHSS) and ectopic pregnancies.

How to cite this article: Panchal S. Volume Ultrasound in Infertility. Donald School J Ultrasound Obstet Gynecol 2022;16(4):312-328.

Source of support: Nil

Conflict of interest: None

Keywords: Duplication abnormalities, Endometrial volume, Sono AVC, Submucosal fibroids, Three-dimensional hystero-salpingo contrast sonography, Three-dimensional sonohysterography

This paper has been previously published as Sonal Panchal: Volume ultrasound in infertility. In: Petanovski Z, Kurjak A. 3D–4D Ultrasound in Gynecology. Jaypee Brothers, New Delhi, 2022, pp 129-147.1

INTRODUCTION

Three-dimensional (3D) US is now a well-established technology, and it has proved its superiority over B-mode US in several applications, including infertility. It is complementary to B-mode and Doppler assessment for pretreatment assessment of the uterus, ovaries, and tube, diagnosis of the cause of infertility, and also for monitoring of treatment cycles in patients with infertility. For the assessment of the female pelvis, transvaginal is the choice of route for scans and the first-line investigation too.

DISCUSSION POINTS

Three-dimensional (3D) US adds information in the following pathologies or situations:

Diagnosis of Uterine Pathologies that Affect Implantation

Amongst the Mullerian abnormalities of the uterus, infertility may occur in cases of septate uterus, t-shaped uterus, and hypoplastic uterus. Other abnormalities like unicornuate uterus and bicorporeal uterus may lead to complications like pregnancy loss, abnormal lie, premature delivery, etc. Correct diagnosis of these lesions is essential because the septate uterus and T-shaped uterus can be treated surgically to the advantage of the patient.

Septate Uterus

In this case, there is a normal fusion of Mullerian ducts, but abnormal absorption of the midline septum leads to a septate uterus. The outer contour of the fundus is normal. Endometrial contour shows indentation on the coronal plane exceeding 50% of the myometrial wall thickness. Myometrial wall thickness is the perpendicular distance measured from the intracorneal line to the highest point of the fundus. If indentation ends short of the internal os, it is a partial septum-subseptate uterus (class U2a)2 (Fig. 1A), but if it extends up to the internal os, it is a complete septum (class U2b) (Fig. 1B).

Figs 1 A and B: (A) Partial septum of the uterus on 3D US omniview; (B) 3D US HD rendered image of complete septum of the uterus

The latter entity may sometimes be associated with the cervical septum. Septate uterus is one of the commonest among Mullerian duct abnormalities, and it has the most clinical impact as it may be the cause of recurrent abortions, premature labor, abnormal fetal lie, and even infertility. In the case of the septum, the length of the remaining uterine cavity was significantly shorter, and the distortion ratio was significantly higher in patients with recurrent miscarriage.3 Surgical correction may be advised when other causes of infertility are ruled out with the history of infertility or recurrent implantation failure. 3D US helps for assessing the exact depth and width of the septum and also the volume of the residual uterine cavity. 3D US, in this case, can also be used for per-operative guidance.

T-shaped Uterus

When the uterine cavity is narrowed down due to thickened lateral walls with a normal uterocervical ratio (2:1), it is a t-shaped uterus. It is measured as the distance between the line joining angle of the endometrial cavity to the internal os and lateral wall on a line drawn perpendicular to the above-said line at the level of the deepest point on the lateral surface of the endometrial cavity. The lateral wall is considered thick when this distance is ≥1.4 times the myometrial wall thickness (Fig. 2A).

Figs 2 A and B: (A) T-shaped uterus on 3D US with a thick lateral wall; (B) Hypoplastic uterus on 3D US with long cervix

Class U1b—uterus infantalis (hypoplastic uterus): narrow uterine cavity without lateral wall thickening in which inverse utero-cervical ratio (Fig. 2B).

Polyps are solid projections from the endometrium into the endometrial cavity. These can be seen on B-mode US, and a single feeding vessel on Doppler confirms the diagnosis. But 3D US with rendering can demonstrate it much better (Fig. 3A), especially when the polyp is large and is confused with endometrial hyperplasia. The latter appears as a long segment of endometrial thickening as compared to a localized lesion, pedunculated, or sessile in the case of polyp (Figs 3B and C).

Figs 3 A to E: (A) Multiplanar and rendered images of the volume of the uterus with a polyp seen as a hyperechoic spot in the endometrial cavity; (B) Large polyp marked by arrow seen in the endometrial cavity on a 3D rendered image of the uterus; (C) Thickening of the entire right lateral endometrial wall seen on the 3D rendered image of the uterus—endometrial hyperplasia; (D and E) Sonohysterography with 3D US rendered image of endometrial cavity showing polyps as marked by arrows

Saline infusion sonohysterography (SIS) combined with 3D US, is the modality of choice for endometrial polyps (Figs 3D and E).

Endometrial polyps may be confused with subendometrial fibroids (T0). These fibroids completely protrude into the endometrial cavity (Figs 4A and B). Apart from B-mode (polyp is echogenic and the fibroid is hypoechoic) and Doppler (single feeding vessel in polyp and peripheral vascularity in fibroid), 3D can also add to the information for differentiation between the two. Infolding of the junctional zone is seen when the render line is placed in the right plane and suggests the possibility of T0 fibroid (Fig. 4C).

Figs 4 A to C: (A) Three-dimensional (3D) rendered image of the endometrial cavity with central round hypoechoic lesion- endometrial fibroid; (B) 3D rendered image of the endometrial cavity with central round hyperechoic lesion- endometrial polyp; (C) 3D rendered image of the endometrial cavity with a roundish echogenic lesion in the endometrial cavity surrounded by a hyperechoic margin with a gap on the fundal aspect of the endometrial cavity, infolding of the junctional zone—a sign of endometrial fibroid

Endometrial Synechiae

Endometrial synechiae/adhesions may be due to surgical insult or due to chronic inflammation. Because of the apposition of the endometrial walls and persistently thin endometrium, synechiae are difficult to identify on B-mode US. 3D US on the coronal plane may help (Fig. 5A). But 3D with SIS gives the best demonstration of the diagnosis (Fig. 5B).

Figs 5 A and B: (A) Three-dimensional (3D) US rendered image of the endometrial cavity with synechiae shown by arrows; (B) 3D US rendered image of the endometrial cavity with sonohysterography with synechiae shown by arrows

Chronic inflammation in the endometrium—CE for which tuberculosis is one of the commonest causes in some parts of the world. May it be imaging criteria or laboratory criteria, none have been conclusive or foolproof for the diagnosis of tuberculosis. But certain US criteria have been found to be more commonly associated with tuberculosis:

  • Persistently thin endometrium.

  • Disrupted endometrial-myometrial junction.

  • Vertically oriented interstitial part of the tube.

  • Echogenic flecks in the endometrium.

  • Echogenic flecks in the myometrium.

  • Avascular myometrial cysts.

  • Fluid in the endometrial cavity in the mid-proliferative phase (day 6–10).

  • Echogenic inner layer of the endometrium.

  • Micropolyposis.

  • Endometrial scarring.

  • Contracted endometrial cavity.

Of these, the ones that are seen on 3D US are shown in Figure 6.

Figs 6 A to E: (A) Grossly contracted endometrial cavity; (B) T-shaped cavity; (C) Scarred endometrium; (D) Vertical orientation of interstitial part of the tube (arrow); (E) Endometrial calcifications (arrows)

Adenomyosis

It is diagnosed by:

  • Symmetrical or asymmetrical thickening of the myometrium.

  • Heterogeneous myometrial echogenicity.

  • Hyperechoic lines, dots or islands, and cysts in myometrium (Figs 7A and B).

  • Fan shadows (Fig. 7C).

  • Irregularity or obliteration of the junctional zone (Figs 7D and E).

  • Question mark sign of uterus.

  • Translesional vascularity—seen as firework lights on 3D power Doppler (Fig. 7F).

  • Vessels with a larger diameter than normal spiral vessels.

Figs 7 A to F: (A)Tomographic US imaging with volume contrast imaging of the sagittal plane of the uterus showing myometrial heterogenicity; (B) Myometrial heterogenicity seen on coronal plane rendered image (sideward arrows), junctional zone obliteration (upside down arrow); (C) Fan shadows seen on coronal plane rendered image of the uterus (arrow); (D) Endometrial strands extending to the myometrium, seen on coronal plane rendered image of the uterus (arrow); (E) Junctional zone irregularity seen on sagittal plane volume contrast imaging; (F) Firework light-like vascularity of adenomyosis as seen on 3D power Doppler

These features are seen on two-dimensional (2D) US but are much better demonstrated using the volume contrast imaging in A (volume contrast imaging in A plane). Irregularity of the junctional zone is one of the first signs to appear and is considered to be diagnostic. 3D US has made it possible to evaluate the junctional zone in detail, comparable to that with MRI. Irregularity of the endometrio-myometrial junction zone thickness and endometrial strands extending into myometrium is also seen on the 3D US.

Similar criteria that are used with MRI can now be used with 3D US also for diagnosis of adenomyosis. The difference in the junctional zone thickness at two different places around the endometrium of >4 mm or a junctional zone thickness of 12 mm has 88% sensitivity and 85% accuracy for the diagnosis of adenomyosis.4 MR imaging is an accurate, noninvasive modality for diagnosing adenomyosis with high sensitivity (78–88%) and specificity (67–93%).5,7

The sensitivity and specificity of MRI in diagnosing adenomyosis are similar to those for sonography and have been reported as 77.5 and 92.5%, respectively.8 These criteria are more reliable in the mid cycle when normally the junctional zone thickness is the lowest.

Fibroids

Well-defined, capsulated, roundish, and hypoechoic lesions that may be subserosal, intramural, or submucosal. A 3D US has a role in demonstrating the exact location of the fibroid and its impact on the endometrium. Submucosal fibroids may distort or invade the endometrial cavity. This distortion or invasion depends on the location and size of the fibroids. The 3D US shows endometrial affection by the fibroid very clearly (Fig. 8). This not only helps in deciding whether the fibroid can be a cause of fertility problems or not but also helps to decide the route of surgery.

Figs 8 A and B: Fibroids distorting the endometrial cavity, seen on a 3D surface and HD live rendering

Three-dimensional (3D) saline contrast hysteroscopy provides important information about the size and location of these fibroids. Lasmar’s score9 for submucous fibroids and size, topography, extension, penetration, wall (STEPW) classification that evaluates the size, topography, extension, penetration, and lateral wall involvement is being used widely to decide the surgical plan (Fig. 9). The scoring system is demonstrated in the pictures below.

Fig. 9: Diagrammatic representation of STEPW classification9

Three-dimensional (3D) US works excellently for accurate fibroid mapping. Using transparent mode in combination with surface texture or surface smooth can show the endometrial contour, and both the myometrial walls with fibroids as hypoechoic round areas when the render line is placed on the wall of the uterus that is close to the probe and the render box is large enough to include the entire uterus (Fig. 10).

Fig. 10: Three-dimensional (3D) US rendered image, using transparent mode in combination with surface texture render mode, can show the endometrial contour (dashed line) and both the myometrial walls with fibroids (arrow)

Local adenomyoma may often be confused with degenerated fibroid. A radial or irregular vascular arrangement is suggestive of adenomyoma whereas a circular arrangement with intralesional vascularity is suggestive of a fibroid (Fig. 11).

Figs 11 A and B: (A) Color Doppler and 3D color Doppler of degenerated fibroid—circular arrangement of peripheral vessels; (B) HD flow and 3D HD flow of adenomyosis showing translesional vessels

Leiomyosarcoma (fibroid with malignant change) is very difficult to differentiate from degenerated fibroids, as both show heterogeneous echogenicity and abundant heterogeneously distributed vascularity. Though when leiomyosarcoma starts invading the surrounding myometrium, the pseudocapsule shows discontinuity or is completely absent. This breach in the capsule can be demonstrated well by 3D US (Fig. 12).

Fig. 12: Breach in the capsule of the fibroid suggesting the possibility of malignant change

Uterine Scar

Assessment of not completely or inadequately healed uterine scars is important. However, 2D US shows the gap in the scar, its exact width, and depth and can be best evaluated by 3D US (Fig. 13). Rarely may one see scars that have been converted into fistulae, and the demonstration of this can be best done by 3D US.

Figs 13 A and B: Uterine scar as marked by an arrow on omniview (A) and rendered (B) 3D US image

Cervical Lesions

On 3D US, the cervix is best visualized when the probe is not pressed on the uterus but is held a little away from cervical lips, especially when there is fluid in the vagina. This demonstrates cervical fibroid and cervical polyp well (Fig. 14). The demonstration can be made even more clear with gel sonography.

Figs 14 A and B: (A) Three-dimensional (3D) rendered image of the cervix in coronal with polyp marked by an arrow; (B) 3D rendered image of the cervix in axial plane showing cervical fibroid (arrow)

Diagnosis of Ovarian Lesions that Affect Fertility

It is important to mention here that the diagnosis of most ovarian lesions does not require 3D US. A 2D US with Doppler almost always leads to diagnosis. But 3D US has a role in the demonstration of certain features that may support the diagnosis or explain the anatomy better.

Endometriomas or chocolate cysts are thick wall cysts with internal echoes which may or may not show movements of the particles contained. They may sometimes appear very similar to corpus luteum or hemorrhagic cysts but more often show low-level homogenous internal echogenicity or even show a vertical differentiation of two different types of echogenicity, described as vertical fluid level. These are painful on probe pressure and may show calcified flecks in the wall. 3D helps to see the irregularity of the wall inside the lesion. 3D power Doppler shows typical short-coursed vessels forming a bird’s nest appearance (Fig. 15A).10 This is typically different from the vascular pattern seen in the corpus luteum, which is like a close-knit basket (Fig. 15B).

Figs 15 A and B: (A) Three-dimensional (3D) power Doppler image of endometrioma; (B) 3D power Doppler image of corpus luteum

Cysts with Solid Components or Septa

In this group are benign tumors like dermoids, cystadenomas, endometrioid tumors, and malignant masses of ovaries. 3D US has an important role to play in demonstrating the typical features of these lesions. 3D US more efficiently shows the internal characteristics of the wall, excludes any projections to confirm the location of the lesion, and establishes the relation of the lesion to the surrounding anatomy (Fig. 16).

Figs 16 A to C: Three-dimensional (3D) US rendered image of the cystic ovarian lesions showing mass irregularities or solid components

Dermoids have thick walls with echogenic material in the lumen, and regional diffuse bright echoes with or without acoustic shadowing due to hair clumps or fat in Rokitansky’s protuberance (Fig. 17) fluid level may be seen. Hyperechoic lines and dots may be seen due to hair.11-15

Figs 17 A to D: (A) Dermoid cyst showing hyperechoic lines; (B) 3D rendering showing teeth in dermoid cyst; (C) 3D rendered image of the dermoid showing fat globules in a dermoid cyst; (D) 3D US volume with niche mode showing heterogeneous consistency of dermoid cyst

A morphologic scoring system has been devised by Kurjak et al. with a sensitivity of 93.1% and specificity of 99.4% and can be marginally increased to a sensitivity of 99% and specificity of 99.8%, including color Doppler.16 About 72% of cystic teratomas are avascular, or if vascularity is present, it is of high resistance.

Diagnosis of Tubal Pathologies

Infective lesions lead to hydrosalpinx and complex tubo-ovarian masses, ultimately in which the ovary and tube cannot be independently identified, and the mass has solid and cystic components.

Three-dimensional (3D) US can be very useful in these cases to confirm the diagnosis of hydrosalpinx and also to identify the partial septations caused by haustral folds of the tube (Figs 18A to C). Rendering may be done in minimum mode or inversion mode. SonoAVC (automated volume calculation) may be used to calculate its volume (Figs 18D and E).

Figs 18 A to E: (A) Three-dimensional (3D) US rendered image of hydrosalpinx in HD live mode; (B) Minimum mode rendering of hydrosalpinx; (C) Inversion mode rendering of the same lesion as in subpart B, and D hydrosalpinx is seen on 3D US; (E) 3D US image with SonoAVC to calculate the volume of hydrosalpinx

Tubal Patency Assessment

Tubal pathology is a cause of subfertility in 25–35% of subfertile couples. Evaluation of fallopian tubes, therefore, forms an essential part of the evaluation of a subfertile female. US is also used for the assessment of tubal patency. Power Doppler with 3D US creates a good graphic presentation of fallopian tubes when saline is injected into the uterine cavity in pulses (Fig. 19A). 3D HyCoSy, a recently evolved procedure, has several advantages over the routine HyCoSy. It filters out the broadband ultrasonic signals from surrounding tissue, and only the tubes are imaged that stand out being filled with microbubbles.17 Using positive contrast, spillage of hyperechoic contrast in a completely anechoic pelvic cavity is very clear. Moreover, the contrast remains for a few seconds, and therefore 3D acquisition can be made, making the visualization of the whole tube possible (Figs 19B and C).18

Figs 19 A to C: (A) Three-dimensional (3D) power Doppler HyCoSy; (B) HD live rendered image of 3D HyCoSy; (C) HD live rendered image of 3D HyCoSy with silhouette mode

A study by Exacoustos et al. has also shown that hysterosalpingography and HyCoSy had the same high concordance as laparoscopy of 86.7% and 86.7%, respectively.19

Large studies have reported that 3D-HyCoSy is highly accurate with 100% sensitivity, 67% specificity, 89% pulse pressure variation, and 100% negative predictive value for tubal patency and concordance rate with laparoscopy of 91%.20

Polycystic Ovaries

According to the European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine consensus 2018,21 polycystic ovarian disease consists of various different phenotypes, and in the majority, US showing polycystic ovaries was important.

A polycystic ovary on US, according to this consensus, is an ovary that is 10 cc in volume and/or has >20 antral follicles of 2–9 mm in diameter. After the volume of the ovary is acquired by 3D US, VOCAL software is used to calculate the ovarian volume. VOCAL calculates the volume of any structure by rotating it 180°. A rotating step of 6–30° can be selected. A circumference is drawn around the structure of interest at every step of rotation, and at the end of 180°, the total volume is calculated by the scanner computer (Fig. 20A).

Figs 20 A and F: (A) Three-dimensional (3D) US acquired volume of the ovary with VOCAL calculated volume calculation of the ovary; (B) VOCAL calculated volume calculation of the ovary rendered in inversion mode showing multiple follicles; (C) SonoAVC of volume ovary showing color-coded follicles; (D) Result sheet of SonoAVC showing three orthogonal diameters, mean diameter, and volume of each follicle; (E) VOCAL calculated the volume calculation of the ovary, with a calculation of stromal volume using threshold volume software; (F) VOCAL calculated the volume calculation of the ovary, with the calculation of VI, FI, and VFI values using volume histogram software

Amongst the morphological features of polycystic ovaries are the follicular number per ovary of more than 12 according to the old consensus and more than 20 per ovary according to the 2018 consensus, the follicular arrangement that may be peripheral or generalized and stromal abundance.

Follicles can be demonstrated by inversion mode (Fig. 20B). More exact value of AFC was acquired when counted by 3D US by SonoAVC (Fig. 20C). This is based on inversion mode and color codes the follicles. Apart from this SonoAVC also calculates the size of each follicle that is important for the understanding of the variable biochemical derangement in various patients with polycystic ovary syndrome (PCOS). The result sheet shows the x, y, and z-axis diameter, mean diameter, and volume of each follicle (Fig. 20D).

Stromal abundance is also an important feature of polycystic ovaries. Patients having long-standing PCOS and long-standing anovulation have more dense stroma, and a cardinal feature has been shown to be the presence of a bright, highly echogenic stroma on transvaginal US.22 Stromal hypertrophy is recognized as a frequent and specific feature in ovarian androgenic dysfunction.23 This can be assessed by stromal echogenicity, stromal area, and stromal volume. But the most accurate assessment of stromal abundance can only be with ovarian and stromal volume by 3D US. It has the potential to address these points and improve the sensitivity and specificity of US in the diagnosis of PCOS.24

Both total ovarian volume and stromal volume during the early follicular phase are significantly higher in women with PCOS.25 Ovarian volume can be calculated by VOCAL as mentioned earlier, and applying threshold volume to this can calculate the stromal volume (Fig. 20E). After the volume is calculated by VOCAL when threshold volume is activated, pigment appears on the VOCAL calculated volume. Applying threshold volume on the same VOCAL calculated volume will define stromal volume when the threshold is set to differentiate follicles from the rest of the ovarian tissue. The threshold is so adjusted that the pigmented area fills up all the follicles and only the follicles. On the screen, above the threshold and below the threshold volumes are displayed. Below the threshold is the follicular volume and above the threshold is the stromal volume. In PCOS patients, a strong and similar correlation is seen between ovarian and stromal volumes to fasting and postprandial insulin levels.26

Three-dimensional (3D) US has clearly shown higher AFC (median 16.3 vs 5.5 per ovary), ovarian volume (12.56 vs 5.6 mL), stromal volume (10.79 vs 4.69 mL), and stromal vascularization (vascularity index (VI) 3.85 vs 2.79%, vascularity flow index (VFI) 1.27 vs 0.85) in PCOS patients.27 These values are calculated by volume histogram applied to VOCAL calculated volume (Fig. 20F).

Assessment of Ovarian Reserve and Response

According to a study by Kupesic et al., predictors of ovarian response are:28

  • A number of antral follicles.

  • Stromal flow: stromal flow index (FI).

  • Total ovarian stromal area.

  • Total ovarian volume.

In that order of importance—this means that the most important predictors of ovarian response can be most precisely assessed by 3D US and 3D power Doppler.

Three-dimensional (3D) US provides a new method for objective quantitative assessment of follicle count, ovarian volume, stromal volume, and blood flow in the ovary.29 SonoAVC for the assessment of the ovarian reserve can be made simpler and more precise by using SonoAVC antral (Fig. 21). This software allows grouping the follicles into a particular size that can be designed and that helps to ignore follicles larger or smaller than the defined limit automatically.

Fig. 21: Sonography-based automated volume count (SonoAVC) antral showing sizewise two different groups of follicles in two colors, yellow and white

On the calculated ovarian volume with power Doppler, applying volume histogram gives values of 3D-power Doppler indices, VI, FI, and VFI. Measurement of ovarian stromal flow in the early follicular phase is related to subsequent ovarian response in IVF treatment (Fig. 20F).24 Kupesic et al. have shown a correlation between the ovarian stromal flow index and the number of mature oocytes retrieved in IVF cycles and pregnancy rates. Stromal FI (<11 low responders, 11–14 good, and >15 at risk of OHSS).32 Another group has demonstrated that VI, FI, and VFI of the ovary were significantly related to ovarian response to stimulation.25

These all together help to decide the stimulation protocol and also to decide any additional or supportive therapy required for a particular patient.

Assessment of Follicular Maturity

Three-dimensional (3D) US and 3D power Doppler have been used for the assessment of preovulatory follicles. In 3D, the follicular volume of 3–7.5 cc has been found to be optimum in our study (Fig. 22A).26 Follicular volumes of between 3–7 cc are optimum for oocyte retrieval by VOCAL. The limits of agreement between the volume of the follicular aspirate and the 3D volume of the follicle were +0.96 to −0.43 with 3D and +3.47 to −2.42 by 2D volume estimation.27 Feichtinger et al., in their study, have shown the presence of cumulus in follicles >15 mm by 3D US (Fig. 22B).28 Follicles without visualization of cumulus in all three planes are less likely to contain mature oocytes.

Figs 22 A to D: (A) Virtual organ computer-aided analysis (VOCAL) calculated volume of the follicle; (B) 3D US HD live rendered image of the follicle showing cumulus; (C) 3D power Doppler glass body rendered image of the follicle showing perifollicular vascularity; (D) VOCAL calculated volume of the follicle with volume histogram showing VI, FI, and VFI values for perifollicular flow

It has also been suggested that the follicles containing oocytes capable of producing a pregnancy have a perifollicular vascular network that is more uniform and distinctive.29,30 It is the 3D power Doppler that provides the most precise information about vascularization and follicular blood flow. 3D power Doppler gives a global assessment of the vascularity, or follicular perfusion, both qualitatively (Fig. 22C) and quantitatively (Fig. 22D). We, in our study, had found that even when the follicle appeared mature according to the 2D US and color and pulse Doppler parameters, the pregnancy rates were significantly better only when the follicular volume was between 3 and 7.5 cc, cumulus was present, and the perifollicular VI was between six and 20 and FI was >27.31 A study by Kupesic and Kurjak shows that when the ratio of follicular volume to blood flow index (FV/FI) is between 0.4 and 0.6 the pregnancy rates are 39%, if >0.6, it is 52% and when <0.4 is only 21%.32

Assessing Endometrial Receptivity

The endometrial thickness on the day of the trigger of 8 mm is optimum with a multilayered morphology, preferably grade A or B.33 On color Doppler the endometrium, which is mature, shows vascularity in zone three and four or maybe said in subendometrial and endometrial layers.34 Zaidi et al. found that the absence of flow in the endometrial and subendometrial zones on the day of human chorionic gonadotropin indicates total failure of implantation.35 Our study31 showed that at a endometrial volume of <2 cc, no pregnancies occurred. With an endometrial volume of 2–3 cc, only 16.66% of patients conceived; between 3 and 5 cc, 47%, and when the endometrial volume was between 5 and 7 cc, 61.5% of patients conceived.31 Endometrial volume by 3D US (Fig. 23A) volume calculation of the endometrium may help to correlate the cycle outcome with quantitative parameters rather than endometrial thickness. For endometrial volume, the interobserver variation in definition of internal os was 0.82, and intra correlation coefficient (CC) intraobserver variation was 0.90, the chief source of error being the definition of endometrial margins.35 A study by Raga et al.36 shows pregnancy and implantation rates were significantly lower when the endometrial volume was <2 cc, while no pregnancy was achieved when the endometrial volume was <1 cc.

Figs 23 A and B: (A) Virtual organ computer-aided analysis (VOCAL) calculated volume of the endometrium; (B) VOCAL calculated volume of the endometrium with volume histogram showing VI, FI, and VFI values

Kupesic et al.37 have concluded subendometrial FI of <11 calculated by 3D power Doppler acquired volume of the endometrium with VOCAL (Fig. 23B) as a cut-off limit for uterine receptivity on the day of embryo transfer. No pregnancies occurred when it was <11, and the conception group showed values of 13.2 ± 2.2.37 Wu et al.38 reported that endometrial VFI was more reliable than VI and FI, and the best prediction rate was achieved by a VFI cut-off value of >0.24. Collectively the evidence from various studies suggests that adding 3D and 3D power Doppler for the assessment of follicular maturity and endometrial receptivity improves the outcome of the fertility treatment by assessment of global vascularity.

Prediction of OHSS

Ovarian volumes may also be useful in predicting the risk of OHSS in the preovulatory phase. Even when the age of the patient and the total number of follicles were similar, the ovarian volume was significantly higher in the patients who developed OHSS (271 ± 87 vs 157.30 ± 54.20 mL) (Fig. 24).39

Fig. 24: Three-dimensional (3D) US VOCAL calculated volume of hyperstimulated ovary rendered in inversion mode showing multiple follicles

Diagnosis and Differentiation of Ectopic Pregnancies in the Uterus

Three-dimensional (3D) US especially assists in differentiation between the angular (Fig. 25) and interstitial pregnancy (Fig. 26) and demonstrates scar pregnancy (Fig. 27A), cervical pregnancy, and tubal multiples (Fig. 27B).

Figs 25 A and B, A to C: Angular pregnancy: (A) On omniview (B) On a rendered image

Figs 26 A and B: (A) Interstitial pregnancy shown on omniview; (B) The same pathology seen on surface rendering

Figs 27 A and B: (A) Scar pregnancy—gestational sac in the scar seen on omniview; (B) Tubal twin pregnancy

  • Angular vs interstitial pregnancy.

  • Pregnancy in the scar/over the scar.

  • Cervical pregnancy or abortion in process.

Advantages of 3D US for Imaging of Uterus

  • Improved recognition of anatomy.

  • Accurate characterization of surface features.

  • Coronal plane imaging.

  • Simultaneous visualization of external and internal contour of uterus.

  • Junctional zone detailing.

  • Clear depiction of size and volume.

  • Shorter scanning time.

  • Detailed evaluation of stored data.

CONCLUSION

Three-dimensional (3D) US can better demonstrate uterine lesions like polyps, endometrial synechiae, and fibroids. Better delineation of endometrio-myometrial junction helps diagnosis of adenomyosis, comparable to MRI. Tubal assessment can be made more effective by adding 3D to HyCOSy. A 3D US is accurate for volume assessment both for the follicle and the endometrium, which are much more reliable parameters than the follicular diameter or endometrial thickness. The presence of cumulus, the presence of which can be confirmed by the 3D US, more easily increases the possibility of the presence of a mature ovum in the follicle. A 3D power Doppler gives an idea about the global vascularity of the follicle and the endometrium.

REFERENCES

1. Petanovski Z, Kurjak A. 3D-4D ultrasound in gynecology. Jaypee Brothers 2022;129–147.

2. Grimbizis GF, Gordts S, Di Spiezio Sardo A, et al. The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies. Hum Reprod 2013;28(8):2032–2044. DOI: 10.1093/humrep/det098

3. Salim R, Woelfer B, Backos M. Reproducibility of three-dimensional ultrasound diagnosis of congenital uterine anomalies. Ultrasound Obstet Gynecol 2003;21(6):578–582. DOI: 10.1002/uog.127. PMID: 12808675

4. Exacoustos C, Brienza L, Di Giovanni A, et al. Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology. Ultrasound Obstet Gynecol 2011;37(4):471–479. DOI: 10.1002/uog.8900

5. Reinhold C, McCarthy S, Bret PM, et al. Diffuse adenomyosis: comparison of endovaginal US and MR imaging with histopathologic correlation. Radiology 1996;199(1):151–158. DOI: 10.1148/radiology.199.1.8633139

6. Outwater EK, Siegelman ES, Van Deerlin V. Adenomyosis: current concepts and imaging considerations. Am J Roentgenol 1998;170(2):437–441. DOI: 10.2214/ajr.170.2.9456960

7. Togashi K, Nishimura K, Itoh K, et al. Adenomyosis: diagnosis with MR imaging. Radiology 1988;166(1 Pt 1):111–114. DOI: 10.1148/radiology.166.1.3336669

8. Bazot M, Cortez A, Darai E, et al. Ultrasonography compared with magnetic resonance imaging for the diagnosis of adenomyosis: correlation with histopathology. Hum Reprod 2001;16(11):2427–2433. DOI: 10.1093/humrep/16.11.2427

9. Lasmar RB, Barrozo PR, Dias R, et al. Submucous myomas: a new presurgical classification to evaluate the viability of hysteroscopic surgical treatment–preliminary report. J Minim Invasive Gynecol 2005;12(4):308–311. DOI: 10.1016/j.jmig.2005.05.014

10. Raine-Fenning N, Jayaprakasan K, Deb S. Three-dimensional ultrasonographic characteristics of endometriomata. Ultrasound Obstet Gynecol 2008;(6):718–724. DOI: 10.1002/uog.5380

11. Atri M, Nazarnia S, Bret PM, et al. Endovaginal sonographic appearance of benign ovarian masses. Radiographics 1994;14(4):747–760. DOI: 10.1148/radiographics.14.4.7938766

12. Patel MD, Feldstein VA, Lipson SD, et al. Cystic teratomas of the ovary: diagnostic value of sonography. AJR Am J Roentgenol 1998;171(4):1061–1065. DOI: 10.2214/ajr.171.4.9762997

13. Quinn SF, Erickson S, Black WC. Cystic ovarian teratomas: the sonographic appearance of the dermoid plug. Radiology 1985;155(2):477–478. DOI: 10.1148/radiology.155.2.3885313

14. Malde HM, Kedar RP, Chadha D, et al. Dermoid mesh: a sonographic sign of ovarian teratoma. AJR Am J Roentgenol 1992;159(6):1349–1350. DOI: 10.2214/ajr.159.6.1442421

15. Bronshtein M, Yoffe N, Brandes JM, et al. Hair as a sonographic marker of ovarian teratomas: Improved identification using transvaginal sonography and simulation model. J Clin Ultrasound 1991;19(6):351–355. DOI: 10.1002/jcu.1870190605

16. Kurjak A, Kupesic S, Babic MM, et al. Preoperative evaluation of cystic teratoma: what does color Doppler add? J Clin Ultrasound 1997;25(6):309–316. DOI: 10.1002/(sici)1097-0096(199707)25:6<309::aid-jcu4>3.0.co;2-g

17. Jeanty P, Besnard S, Arnold A, et al. Air-contrast sonohysterography as a first step assessment of tubal patency. J Ultrasound Med 2000;19(8):519–527. DOI: 10.7863/jum.2000.19.8.519

18. Holz K, Becker R, Schürmann R. Ultrasound in the investigation of tubal patency. A meta-analysis of three comparative studies of Echovist-200 including 1007 women. Zentralbl Gynakol 1997;119(8):366–373.

19. Exacoustos C, Zupi E, Carusotti C, et al. Hysterosalpingo-contrast sonography compared with hysterosalpingography and laparoscopic dye pertubation to evaluate tubal patency. J Am Assoc Gynecol Laparosc 2003;10(3):367–372. DOI: 10.1016/s1074-3804(05)60264-2

20. Chan CC, Ng EH, Tang OS, et al. Comparison of three-dimensional hysterosalpingo-contrast-sonography and diagnostic laparoscopy with chromopertubation in the assessment of tubal patency for the investigation of subfertility. Acta Obstet Gynecol Scand 2005;84(9):909–913. DOI: 10.1111/j.0001-6349.2005.00797.x

21. Teede HJ, Misso ML, Costello MF, et al. International evidence based guideline for assessment and management of polycystic ovarian syndrome 2018. Fertil Steril 2018;110(3):364–379. DOI: 10.1016/j.fertnstert.2018.05.004

22. Buckett WM, Bouzayeb R, Watkin KL, et al. Ovarian stromal echogenicity in women with normal and polycystic ovaries. Hum Reprod 1999;14(3):618–621. DOI: 10.1093/humrep/14.3.618

23. Fulghesu AM, Angioni S, Frau E, et al. Ultrasound in polycystic ovary syndrome–the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study. Hum Reprod 2007;22(9):2501–2508. DOI: 10.1093/humrep/dem202

24. Raine-Fenning NJ, Campbell BK, Clewes JS, et al. The reliability of virtual organ computer-aided analysis (VOCAL) for the semiquantification of ovarian, endometrial and subendometrial perfusion. Ultrasound Obstet Gynecol 2003;22(6):633–639. DOI: 10.1002/uog.923

25. Kyei-Mensah AA, LinTan S, Zaidi J, et al. Relationship of ovarian stromal volume to serum androgen concentrations in patients with polycystic ovary syndrome. Hum Reprod 1998;13(6):1437–1441. DOI: 10.1093/humrep/13.6.1437

26. Panchal SY, Nagori CB. Correlation of ovarian and stromal volumes to fasting and postprandial insulin levels in polycystic ovarian syndrome patients. Int J Infertil Fetal Med 2014;5(1):12–14. DOI: 10.5005/jp-journals-10016-1073

27. Kyei-Mensah A, Zaidi J, Pittrof R, et al. Transvaginal three-dimensional ultrasound: accuracy of follicular volume measurements. Fertil Steril 1996;65(2):371–376. PMID: 8566265.

28. Feichtinger W. Transvaginal three-dimensional imaging. Ultrasound Obstet Gynecol 1993;3(6):375–378. DOI: 10.1046/j.1469-0705.1993.03060375.x

29. Zaidi J, Barber J, Kyei-Mensah A, et al. Relationship of ovarian stromal blood flow at the baseline ultrasound scan to subsequent follicular response in an in vitro fertilization program. Obstet Gynecol 1996;88(5):779–784. DOI: 10.1016/0029-7844(96)00316-X

30. Merce LT, Barco MJ, Bau S, et al. Prediction of ovarian response and IVF/ICSI outcome by three-dimensional ultrasonography and power Doppler angiography. Eur J Obstet Gynecol Reprod Biol 2007;132(1):93–100. DOI: 10.1016/j.ejogrb.2006.07.051

31. Panchal SY, Nagori CB. Can 3D PD be a better tool for assessing the pre HCG follicle and endometrium? A randomized study of 500 cases. J Ultrasound Obstet Gynecol 2006;28(4):504. DOI: 10.1002/uog.3361

32. Kupesic S, Kurjak A. Predictors of IVF outcome by three-dimensional ultrasound. Hum Reprod 2002;17(4):950–955. DOI: 10.1093/humrep/17.4.950

33. Vlaisavljevic V, Reljic M, Gavric Lovrec V, et al. Measurement of perifollicular blood flow of the dominant preovulatory follicle using three-dimensional power Doppler. Ultrasound Obstet Gynecol 2003;22(5):520–526. DOI: 10.1002/uog.225

34. Merce LT, Barco MJ, Kupesic S, Kurjak A. 2D and 3D power doppler ultrasound from ovulation to implantation In Kurjak A, Chervenak F (Eds): Textbook of perinatal medicine. London: Parthenon Publishing, 2005

35. Zaidi J, Campbell S, Pittrof R, et al. Endometrial thickness, morphology, vascular penetration and velocimetry in predicting implantation in an in vitro fertilization program. Ultrasound Obstet Gynecol 1995;6(3):191–198. DOI: 10.1046/j.1469-0705.1995.06030191.x

36. Raga F, Bonilla-Musoles F, Casan EM, et al. Assessment of endometrial volume by three-dimensional ultrasound prior to embryo transfer: clues to endometrial receptivity. Hum Reprod 1999;14(11):2851–2854. DOI: 10.1093/humrep/14.11.2851

37. Kupesic S, Bekavac I, Bjelos D, et al. Assessment of endometrial receptivity by transvaginal color Doppler and three-dimensional power Doppler ultrasonography in patients undergoing in vitro fertilization procedures. J Ultrasound Med 2001;20(2):125–134. DOI: 10.7863/jum.2001.20.2.125

38. Wu HM, Chiang CH, Huang HY, et al. Detection of the subendometrial vascularization flow index by three-dimensional ultrasound may be useful for predicting the pregnancy rate for patients undergoing in vitro fertilization-embryo transfer. Fertil Steril 2003;79(3):507–511. DOI: 10.1016/s0015-0282(02)04698-8

39. Oyesanya OA, Parsons JH, Collins WP. Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome. Hum Reprod 1995;10:3211–3212. DOI: 10.1093/oxfordjournals.humrep.a135890

________________________
© The Author(s). 2022 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.