Fig. 9.1
CL corpus luteum cyst
Typical endometrioma in a reproductive-aged woman is a cyst with ground glass echogenicity, one to four locules, and no solid parts [7]. However, it should be noted that 17 % of endometriomas have a solid component [7]. Vascularization of the solid component is a worrisome finding that requires further investigation. Similar to hemorrhagic cysts, the presence of an endometrioma per se is not an absolute contraindication to OS. Endometrioma excision is associated with a decrease in ovarian reserve, and the recurrence rate is high in the absence of ovarian suppression [8], and one should be aware that the evaluation of ovarian reserve in ovaries with endometrioma might be underestimated, and they frequently provide similar amount of oocytes compared with the contralateral ovary without endometrioma [9]. Therefore, OS with endometriomas in situ is a valid option for most patients. Again, concerns regarding monitoring or oocyte collection can justify surgery prior to OS; we individualize management by taking into account risk of malignancy, current status of ovarian reserve, and laterality of endometriomas in addition to other factors [10].
Anechoic unilocular cysts, which have regular external and internal contours and are located outside but in proximity to the ovary, are most likely paraovarian or paratubal cysts. Differential diagnosis includes hydrosalpinx and peritoneal cysts, also called pseudocysts, which are mesothelial lesions, most often due to pelvic adhesions. A hydrosalpinx can appear similar to a paraovarian/paratubal cyst, but more often they appear as elongated tubular structures, which could have a convoluted external contour (Fig. 9.2). The “cogwheel sign,” i.e., irregular internal contours due to swollen tubal folds, suggests hydrosalpinx rather than a paraovarian/paratubal cyst. A typical feature of hydrosalpinx is the presence of incomplete partial septa [11]. Ideally these are diagnosed before stimulation and decisions are made in advance. However, if such a structure is visualized for the first time during the start scan, we cancel OI and COS cycles until after ruling out/treating hydrosalpinx, except when the aim is cryopreserving oocytes/embryos.
Fig. 9.2
Hydrosalpinx with an endometrioma in the ipsilateral ovary. The arrows point to convoluted external contour and incomplete septa of the hydrosalpinx. Note the unilocular ground glass appearance of the endometrioma. The image belongs to a patient with Herlyn–Werner–Wunderlich syndrome. HS hydrosalpinx, EN endometrioma
9.2.1.2 Assessment of the Endometrium
We systematically scan the uterus from one cornual region to the other in the sagittal plane and observe the endometrial stripe in its entirety. The presence of focal thickenings can represent endometrial polyps or endometrial fragments/clots remaining from menstrual bleeding. If the menstrual bleeding has not ceased yet, we scan the patient again in 24 h to check the endometrial lining. Most clots/endometrial fragments are passed and OS can be started. However, true polyps remain in the same position, and the decision to proceed with OS or cancellation is individualized depending on the size and location of the suspected lesion. A definitive diagnosis requires saline hysterosonography or hysteroscopy.
9.2.2 Monitoring Scans
The frequency and the number of monitoring scans depend on the stimulation protocol and anticipated/observed ovarian response. In general, we do the first monitoring scan one week after the start of OS. Women at risk of poor or hyperresponse are scanned earlier, on the fifth or sixth day of OS, for possible dose adjustments. Likewise, women undergoing a flexible GnRH antagonist COS protocol are scanned earlier, to check whether the criteria to start GnRH antagonist injections has been already met. The assessment includes the number and size of growing follicles and the endometrial thickness and pattern.
9.2.2.1 Monitoring Follicle Growth
We prefer an initial screen of the ovary from one pole to the other for counting the number of follicles. This is done to decrease the risk of some follicles not being counted during the measurement procedure. Once the number of follicles in each ovary is noted, we begin to measure each follicle in the same systematic fashion, i.e., starting from one pole toward the other. In our practice, the average of the maximal diameter and the longest diameter at 90° to the maximal diameter on the same plane is used as the measure of follicle size for OI, SO, and most COS cycles, depending on the extent of multifollicular growth.
Penzias et al. reported that 2D US measurement of follicle diameter had a significant relationship with true volume of spherical and polygonal follicles, but it was less predictive of volume of follicles with ellipsoid conformation [12]. While the majority of follicles have a spherical conformation in OI cycles, many follicles have ellipsoid or irregular conformation in COS cycles with multifollicular growth. Thus, the reliability of 2D measurements of follicle diameter can be limited in COS cycles. We prefer to use the three-dimensional automated volume calculation (SonoAVC, GE, Kretz, Austria) for COS cycles with multifollicular growth. The SonoAVC technology and its use in ART will be mentioned later.
In most cases, we continue monitoring until the ovulation trigger. Regardless of the method of measurement, the size of the leading follicle(s) determines whether another monitoring scan will be required and its timing. Once the follicles reach 14–15 mm size, the expected growth rate is approximately 2 mm/day, and the next monitoring scan can be scheduled based on expected follicle growth [13].
The two important complications of OS are multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) [14–16]. As smaller follicles can also harbor mature oocytes and produce vasoactive mediators following luteinization, their numbers contribute to the risks of both complications. Accordingly, the number of subordinate follicles >11 mm is used as a risk marker dictating the need for preventive measures, e.g., gonadotropin dose adjustment, modification of ovulation trigger, cycle cancellation, etc. [16]. Therefore, we meticulously count the total number of growing follicles. This number, alongside the size of leading follicle(s), also determines the need for further monitoring scans and their timing.
9.2.2.2 SonoAVC for Monitoring Follicular Growth
SonoAVC is an application, which identifies hypoechoic regions within a volume dataset acquired with 3D US. Following capturing a 3D volume of an ovary, SonoAVC automatically analyzes the volume dataset, identifies the boundaries of hypoechoic follicles, and provides estimates of their absolute dimensions. These estimates include the largest diameters in three orthogonal planes, the mean follicular diameter (MFD), the volume of the follicle, and the volume-based diameter (d(V)) of the follicle. The volume calculation is based on the voxel, i.e., 3D equivalent of pixels, count within the identified hypoechoic structure. It therefore represents a true measure of follicular volume. While the MFD is the arithmetic mean of the longest diameters in the three orthogonal planes, d(V) is the diameter of a perfect sphere with the same volume as the follicle that is measured. After calculation of the actual volume of a follicle, SonoAVC reverse calculates the diameter of a perfect sphere, which has the same volume as the follicle by using the relaxed sphere diameter formula mentioned above. An example of SonoAVC measurements is presented in Fig. 9.3.
Fig. 9.3
SonoAVC interface showing color-coding of follicles in the three orthogonal planes and a three-dimensional reconstruction. The upper arrow in the C plane points an underestimated follicle due to internal echoes, and the lower arrow points an extra-ovarian hypoechoic area erroneously recognized as a follicle. Both errors are corrected during post-processing
First a 3D volume of the entire ovary is captured. Once the software is activated and automated measurements are completed, we rotate the ovarian image in the A plane for 360° to identify any errors in automatic identification. Any follicles that are overlooked by the software are manually included using the “add” function. Likewise, if there are hypoechoic regions, e.g., blood vessels adjacent to the ovary or free fluid in pelvis, that are erroneously included in the follicle count, they are manually removed by using the “remove” function. We use “cut” and “merge” functions to trim follicles as needed. Eventually, we prefer to use the MFD by rounding it down to the next mm, in accordance with our previous findings [17].
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