{"@context":"https://schema.org","@graph":[{"@type":"MedicalScholarlyArticle","@id":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e#article","headline":"The role of three‐dimensional ultrasound in assisted reproduction treatment","name":"The role of three‐dimensional ultrasound in assisted reproduction treatment","url":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e","inLanguage":"en","datePublished":"Fri, 26 Mar 2004 00:00:00 GMT","dateCreated":"Fri, 10 Oct 2025 00:00:00 GMT","abstract":"The first stage of many assisted reproduction treatment cycles, prior to ovarian stimulation, is to obtain control over the hypothalamic–pituitary–ovarian axis through the induction of pituitary ‘down-regulation’. This term reflects the internalization and greatly reduced expression of gonadotropin releasing hormone (GnRH) receptors in the pituitary in response to a continuous and highly supraphysiological dose of a GnRH agonist analog. This in turn prevents the recruitment of follicle-stimulating hormone (FSH)-responsive follicles in the ovary and ensures that ovulation cannot occur spontaneously as it also prevents the surge in luteinizing hormone (LH) required to initiate the series of events that lead to the eventual expulsion of the oocyte. This remains, however, a crucial step in treatment, as exposure to high levels of LH also stimulates the resumption of meiosis and is mimicked through a single dose of human chorionic gonadotropin (hCG), which has a similar structure and pharmacodynamic effect but is more readily available. Exposure to hCG is essential prior to the collection of the oocytes to ensure that they are mature and therefore capable of being fertilized when incubated with sperm during in-vitro fertilization (IVF) or when injected with a single sperm in intracytoplasmic sperm injection (ICSI) treatment. This would eventually lead to ovulation in vivo if the oocytes were not physically retrieved and therefore this procedure is critically timed to occur within 34 to 36 h of administration of hCG. Confirmation of adequate down-regulation is essential, therefore, prior to ovarian stimulation and it is invariably determined through a combination of low serum estradiol levels, and a thin endometrium (less than 5 mm) and quiescent ovaries (no follicles above 9 mm) on ultrasound. Yaman et al. used receiver–operating characteristics (ROC) curve analysis to examine the role of three-dimensional endometrial volume measurement in predicting pituitary down-regulation in 46 women undergoing IVF3. Using different estradiol levels to define successful down-regulation they reported the highest sensitivity (100%) and specificity (93.2%) with an endometrial volume of 1.9 cm3 or less in association with an estradiol level below 80 pg/mL. Both sensitivity (95.2%) and specificity (75.0%) were reduced when using the same endometrial volume alongside an estradiol level of 60 pg/mL or less. However, despite offering a new tool for the confirmation of down-regulation, volume measurements proved no better than did a standard measurement of endometrial thickness. More recently, Child et al. showed that endometrial volume out-performed thickness measurements as a predictor of pituitary suppression and non-suppression following down-regulation in 144 women undergoing 164 cycles of IVF treatment4. Using ROC curve analysis at four different estradiol thresholds (100, 150, 200 and 250 pmol/L), they showed volume to be superior to thickness at confirming successful down-regulation when a threshold of 200 pmol/L was used. They concluded that different thresholds may be selected dependent upon whether the aim is to confirm adequate pituitary suppression or to identify those women with non-suppressed cycles. Jarvela et al. examined the effect of pituitary down-regulation in 40 women on ovarian volume, follicle number, vascularity and echogenicity, as assessed by the mean gray value5. Data following a mean duration of pituitary suppression of 16 (range, 14–33) days were compared with those derived from pre-treatment sonography conducted in the late follicular phase between days 8 and 16 of the menstrual cycle. The only consistent significant changes were a reduction in volume of the dominant ovary and an associated increase in the mean gray value in keeping with loss of the dominant follicle. Somewhat surprisingly, there were no differences in the three-dimensional indices of vascularity in either the dominant or the non-dominant ovary, despite the observed differences in volume and grayness. A significant reduction in the number of follicles was observed overall, but this was restricted to those ovaries with a polycystic appearance and the follicular diameters were not taken into consideration. The authors did not test the ability of ovarian volume or vascularity to define successful down-regulation and no data on eventual outcome were given. These issues are potentially important, as evident in the three-dimensional work focusing upon ovarian response. The dose and duration of FSH treatment is dependent upon each individual patient's response to stimulation and is adjusted dynamically during treatment dependent on the number of follicles developing and on the amount of estrogen they produce collectively as measured in the serum. The response and eventual number of mature oocytes retrieved is referred to as the patient's ‘ovarian reserve’. Prediction of ovarian reserve has obvious importance as it allows treatment to be tailored to the individual, potentially increasing the number of oocytes retrieved in those with a low reserve who need increased doses of FSH. This, however, must be balanced against inducing an over-response, which in extreme circumstances may lead to ovarian hyperstimulation syndrome, a serious and significant cause of morbidity and even mortality. The majority of reproductive medicine units adopt a standard approach to this based on age and a measurement of FSH during the early follicular phase in the 6 months prior to treatment. Patients in their twenties are usually offered two ampules of FSH (150 IU), those over forty are started on four ampules (300 IU), and the remainder receive three ampules (225 IU). These doses may be increased in those women with a pre-treatment FSH level above 10 IU/L, or reduced if the patient is thought to have polycystic ovarian syndrome, which is associated with a significantly greater chance of ovarian hyperstimulation syndrome. Accepting the expected reduction in ovarian reserve with age, patients generally respond in a similar fashion during subsequent treatment cycles and this may be used to modify protocols accordingly in those with prior aberrant responses. However, a certain degree of intrasubject variability occurs and a significant number of patients do not have previous treatment cycles to facilitate such comparison. The possibility of being able to predict outcome or ovarian reserve has attracted a great deal of attention and several potential markers have been suggested including those derivable from ultrasound data. Of the ultrasound markers suggested as predictive of ovarian response, the three that have been specifically addressed by three-dimensional ultrasound studies are ovarian volume, antral follicle counts and ovarian blood flow. Schild et al. examined the role of ovarian volume measurements made prior to ovarian stimulation but after down-regulation in 152 IVF cycles6. Ovarian volume did not correlate with IVF outcome and they were surprised to note a non-significant trend towards smaller ovarian measurements in the conception group. Subgroup analysis comparing absolute ovarian size revealed a pregnancy rate of only 6.7% (1/15) in patients with a minimum unilateral ovarian volume of ≤ 3 cm3, which represented a single standard deviation below the mean, vs. 21.9% (30/137) in patients with an initial minimum ovarian volume > 3 cm3. This difference was not significant, however, and cancellation rates due to poor ovarian response or failed fertilization were similar in both groups. Pellicer et al. also found no role for ovarian volume measurements as an adjunct to conventional markers of ovarian reserve in a group of ‘low responders’ in one of the first studies to use three-dimensional ultrasound7. Ten women defined as low responders, having developed no more than three follicles in two previous standard treatment cycles, were compared with eight control patients who had developed seven or more follicles previously, on day 3 of the menstrual cycle. In both groups all women were under the age of 35 with normal basal serum FSH levels. Whilst ovarian volume measurements were similar between the two groups, the number of ‘selectable follicles’ measuring 2–5 mm and the total number of antral follicles were significantly decreased in the low responder group, who also demonstrated significantly higher serum FSH levels despite having values within the normal range. Whilst the number of selectable follicles appears to be a potential discriminator of women with an impaired ovarian reserve, it is not possible to conclude from this study whether three-dimensional imaging offers any significant advantage over conventional ultrasound, as all follicle counts were conducted using the multiplanar display specific to three-dimensional ultrasound. Dumesic et al. found early follicular phase antral follicle counts not only to be superior to ovarian volume measurements in predicting ovarian response to FSH but also to be linked to androgen and insulin release8. In 25 ‘normal’ ovulatory women, both pre-treatment antral follicle count and serum androstenedione were positively correlated with subsequent total and mature oocyte numbers, whilst FSH, LH, inhibin A and B, testosterone, dehydroepiandrosterone sulfate, estradiol and total ovarian volume were unrelated to either. Insulin release in response to a standard oral glucose tolerance test (OGTT) was negatively correlated with total oocyte number but unrelated to mature oocyte number after controlling for antral follicle number. The antral follicle count, however, remained significantly correlated with mature oocyte number after controlling for post-OGTT insulin release, again demonstrating its independent power of prediction. Pellicer et al. defined ‘selectable follicles’ as those measuring 2 to 5 mm7, as it is at this stage that they become increasingly responsive to gonadotropins9. Pre-antral follicles measuring 0.15 mm take approximately 70 days to reach a size of 2 mm and during this time they remain relatively unresponsive to the cyclical changes in FSH and LH, demonstrating minimal granulosa cell proliferation and low steroidogenic activity. During the normal menstrual cycle the follicle destined to ovulate is recruited during the luteal phase of the preceding cycle from a pool of 3–11 antral follicles per ovary and is selected during the early follicular phase of the subsequent cycle10. With the exception of this dominant follicle, all healthy follicles are invariably 6 mm or less and many larger follicles are indeed atretic11. The relative proportion of follicles of different diameters may therefore also be an important determinant of response and outcome. Pohl et al. used three-dimensional ultrasound to quantify the number of follicles of various diameters in 113 patients following down-regulation and prior to ovarian stimulation12. Patients with a higher number of follicles measuring between 5 and 10 mm were younger (P < 0.01), had a significantly higher number of oocytes retrieved (P < 0.001) and were more likely to conceive (P < 0.05). A significant correlation was noted between follicle size and serum estradiol level in follicles measuring 11 mm or more (P < 0.05), and patients with follicles predominantly larger than 11 mm were more likely to have treatment cancelled due to a poor ovarian response. There is no doubt, therefore, that antral follicle counts and their relative diameters are important predictors of ovarian reserve and they may be measured with an acceptably high level of agreement both between and within observers. Three-dimensional ultrasound, however, has not been shown to offer any significant advantage over two-dimensional imaging in determining the number of antral follicles even at higher counts when interobserver reliability is reduced13. If we accept that three-dimensional assessment of ovarian volume and antral follicle count offers no significant advantage over conventional assessment, then the only other parameter to support a role for three-dimensional ultrasound is the assessment of vascularity through the quantification of the power Doppler signal. Jarvela et al. used three-dimensional power Doppler angiography to compare ovarian vascularity in 33 women with normal ovarian reserve, defined as the presence of five or more follicles measuring 2–5 mm, with 12 women with fewer than five such sized follicles14. Patients were examined after pituitary down-regulation and during gonadotropin stimulation. The number of oocytes retrieved correlated with the antral follicle count (R = 0.458, P < 0.01) and ovarian volume (R = 0.388, P < 0.05), but not with ovarian vascularity. However, whilst all three indices of vascularity were shown to increase significantly during gonadotropin stimulation in the group with normal ovarian reserve, this was not observed in the low responders. The increase in the ovarian power Doppler signal during gonadotropin stimulation was related to the antral follicle count, however, reinforcing the importance of this marker as an independent variable. Kupesic and Kurjak also demonstrated that the antral follicle count is a better predictor of response than are ovarian volume or vascularity in their study of 56 women with normal basal serum FSH concentrations undergoing their first cycle of IVF15. Whilst several factors were found to be significant, including the ovarian stromal flow index, peak estradiol on the day of hCG administration, total ovarian volume, total ovarian stromal area and age, the best predictor was total antral follicle number. When combined, these six parameters were able to predict a favorable outcome in 50% (11/22) of patients and a poor outcome in 85% (29/34) of patients. In a subsequent publication, ovarian volume, total follicle number and stromal vascularity were all shown to decrease with advancing age in the same group of patients16. However, within each individual age group the number of oocytes retrieved and the subsequent conception rate were greater in those patients with a greater ovarian volume, a higher number of antral follicles and more marked ovarian stromal vascularity. Whilst the value of three-dimensional ultrasound in predicting suboptimal ovarian response is limited, it may have a role in identifying those women who are prone to an exaggerated response. Pan et al. used three-dimensional ultrasound on the day of hCG administration to study patients demonstrating an exaggerated response to controlled ovarian stimulation, as defined by an estradiol level above 3000 pg/mL on the day of hCG administration or the retrieval of 15 oocytes or more17. Ovarian volume and vascularity were found to be significantly higher in 23 so called ‘hyper-responders’ compared with 35 normally responsive controls (volume, 48.48 ± 25.87 vs. 24.38 ± 9.68; vascularization index, 1.18 ± 0.60 vs. 0.63 ± 0.61; flow index, 50.23 ± 2.81 vs. 43.19 ± 7.81; vascularization flow index, 2.27 ± 1.08 vs. 1.25 ± 1.18). Further work is warranted but probably using a more generally agreed definition of ‘hyperstimulation’ in a larger patient population as the prevalence of overstimulation will be less. If patients susceptible to an over-response can be prospectively identified in a reliable manner and excluded, higher doses of FSH may be employed for standard ovarian stimulation protocols than are currently used in the remaining patients. Fertilization of an oocyte is confirmed by the presence of two pronuclei 18–24 h after IVF or ICSI. The embryos are allowed to develop in vitro until the second or third day after oocyte retrieval when most units would transfer to the recipient uterus a maximum of two embryos selected on the basis of their quality as determined by a subjective grading system. Embryos may, however, be cultured for up to 5 days and transferred at the blastocyst stage in the hope of achieving a higher implantation rate for every single embryo replaced. The chance of the implantation occurring is not only dependent upon the embryo's stage and grade but also on the endometrium. Just how important ‘endometrial receptivity’ is in the overall process remains uncertain, but the endometrium is likely to play more than a passive role18. This is substantiated by the fact that implantation is unlikely to occur in the presence of an endometrium measuring less than 5 mm in diameter19. Conception is not necessarily more likely in women with a thicker endometrium and therefore the role of endometrial thickness measurement is really restricted to its negative predictive value. Studies examining the role of three-dimensional ultrasound have compared measurements of endometrial volume and vascularity with thickness measurements as the current standard. Schild et al. compared endometrial thickness and endometrial volume in a total of 47 IVF cycles on the day of oocyte retrieval20. There were no significant differences between the group of 15 patients that conceived (31.9%) and the remaining 32 non-pregnant women in terms of the mean endometrial thickness (10.8 ± 2.3 mm vs. 11.8 ± 3.4 mm) or volume (4.9 ± 2.2 cm3 vs. 5.8 ± 3.4 cm3). In keeping with the current evidence there was a wide range of endometrial thickness measurements in both pregnant patients (6.9–16.0 mm) and non-pregnant patients (6.5–21.1 mm), and no obvious correlation between estradiol concentrations and endometrial thickness or volume. Yaman et al. reported similar findings with no differences in endometrial volume (4.16 ± 1.97 cm3 vs. 4.53 ± 1.79 cm3), endometrial thickness (11 ± 2 mm vs. 11 ± 2 mm) or serum estradiol (1686 ± 1057 pg/mL vs. 1883 ± 1147 pg/mL) between 21 pregnant and 44 non-pregnant women on the day of hCG administration21. However, whilst there was no absolute endometrial thickness required for pregnancy a minimum endometrial volume above 2.5 cm3 favored pregnancy. Raga et al. also described a cut-off point in endometrial volume in their study of 72 patients on the day of embryo transfer22: Implantation rates were significantly lower (P < 0.05) in those women with an endometrium measuring less than 2 cm3 and no pregnancies were observed at volumes below 1 cm3. volume measurement would to offer a and negative predictive value to endometrial thickness in predicting implantation after embryo transfer therefore upon its sensitivity in the Kupesic et al. reported that more predictive be derived at the time of embryo transfer when three-dimensional power Doppler was used to quantify endometrial In successful conception cycles were associated with a significantly higher endometrial flow ± 2.2 vs. ± P < 0.05). This study the from three-dimensional blood flow analysis as assessment of endometrial thickness and volume or in combination with Doppler findings in the of a offered any power in the of successful cycles. et al. found three-dimensional power Doppler angiography to be an important determinant of endometrial on the day of hCG administration in patients undergoing their first IVF The vascularization flow proved the best predictor of being superior to the vascularization index, flow and endometrial volume in ROC curve the only study not to any from three-dimensional power Doppler in determining the of the endometrium was that of et in which the power Doppler signal was through of the on the day of oocyte retrieval in patients undergoing IVF all indices of blood flow were significantly higher during the but this did not into any in terms of identifying those women with successful cycles. were relatively however, and this approach assessment, not only in terms of the absolute quantification of power Doppler but also through the of and the of the signal following a of as this is the more to examine Three-dimensional assessment of endometrial vascularity may even be used to predict endometrial and eventual outcome prior to ovarian stimulation. Schild et al. used three-dimensional power Doppler angiography to examine the area at the of down-regulation and prior to ovarian stimulation in IVF patients conceived and in these women all three indices of vascularity were significantly lower than they were in cycles (P < 0.05) with the flow being the predictive of (P < 0.05). measurements again were not correlated with outcome. These findings may a more pituitary suppression in those that conceive but are more likely to to patients that respond more to down-regulation are more likely to respond to FSH stimulation, an effect that be through different of expression within the hypothalamic–pituitary–ovarian This study was also in that it was the first to examine blood defined as the within 5 mm of the This was through the of the which the within an three-dimensional the of the and the fact that the endometrial is more than it is that this proved reliable and revealed such significant that vascularity did between the groups. If we accept that three-dimensional analysis of endometrial vascularity and endometrial volume do have a role in determining endometrial then we must how such may be used to implantation and cycle would be to a in which treatment, embryo was based upon measurement of endometrial volume or endometrial thickness. If conception were unlikely to occur below certain then the transfer of embryos be and all potentially embryos for use in subsequent embryo cycles. However, the rate of such treatment remains below that for the transfer of A study examining outcome based upon the cancellation of embryo transfer cycles dependent on measurements of endometrial volume and vascularity in with conventional markers would be more but this has for the or the possibility is to the dose or duration of ovarian stimulation, or to endometrial through the administration of have been including and A significant number of studies have been to examine the value of and blood flow measurements specific to three-dimensional ultrasound in assisted reproduction treatment. of these studies are and therefore but they do offer into how this imaging may be used to outcome for patients undergoing treatment. studies are indeed essential following the of any new as they for other to their studies and ensure the of new Ovarian volume measurements do not to offer any advantage over similar measurements derived from two-dimensional data and stromal blood flow is less in ovarian response compared with antral follicle However, the through the quantification of the power Doppler signal within the endometrium and to significantly between cycles and conception cycles and between the various of treatment. to three-dimensional ultrasound for evidence of above that of current but this can only be by do not accept that of three-dimensional imaging are for its but to that they its potential and to its in to the of patients. is essential, therefore, that work in this area is and that any findings are prospectively in controlled","description":"The first stage of many assisted reproduction treatment cycles, prior to ovarian stimulation, is to obtain control over the hypothalamic–pituitary–ovarian axis through the induction of pituitary ‘down-regulation’. This term reflects the internalization and greatly reduced expression of gonadotropin releasing hormone (GnRH) receptors in the pituitary in response to a continuous and highly supraphysiological dose of a GnRH agonist analog. This in turn prevents the recruitment of follicle-stimulating hormone (FSH)-responsive follicles in the ovary and ensures that ovulation cannot occur spontaneously as it also prevents the surge in luteinizing hormone (LH) required to initiate the series of events that lead to the eventual expulsion of the oocyte. This remains, however, a crucial step in treatment, as exposure to high levels of LH also stimulates the resumption of meiosis and is mimicked through a single dose of human chorionic gonadotropin (hCG), which has a similar structure and pharmacodynamic effect but is more readily available. Exposure to hCG is essential prior to the collection of the oocytes to ensure that they are mature and therefore capable of being fertilized when incubated with sperm during in-vitro fertilization (IVF) or when injected with a single sperm in intracytoplasmic sperm injection (ICSI) treatment. This would eventually lead to ovulation in vivo if the oocytes were not physically retrieved and therefore this procedure is critically timed to occur within 34 to 36 h of administration of hCG. Confirmation of adequate down-regulation is essential, therefore, prior to ovarian stimulation and it is invariably determined through a combination of low serum estradiol levels, and a thin endometrium (less than 5 mm) and quiescent ovaries (no follicles above 9 mm) on ultrasound. Yaman et al. used receiver–operating characteristics (ROC) curve analysis to examine the role of three-dimensional endometrial volume measurement in predicting pituitary down-regulation in 46 women undergoing IVF3. Using different estradiol levels to define successful down-regulation they reported the highest sensitivity (100%) and specificity (93.2%) with an endometrial volume of 1.9 cm3 or less in association with an estradiol level below 80 pg/mL. Both sensitivity (95.2%) and specificity (75.0%) were reduced when using the same endometrial volume alongside an estradiol level of 60 pg/mL or less. However, despite offering a new tool for the confirmation of down-regulation, volume measurements proved no better than did a standard measurement of endometrial thickness. More recently, Child et al. showed that endometrial volume out-performed thickness measurements as a predictor of pituitary suppression and non-suppression following down-regulation in 144 women undergoing 164 cycles of IVF treatment4. Using ROC curve analysis at four different estradiol thresholds (100, 150, 200 and 250 pmol/L), they showed volume to be superior to thickness at confirming successful down-regulation when a threshold of 200 pmol/L was used. They concluded that different thresholds may be selected dependent upon whether the aim is to confirm adequate pituitary suppression or to identify those women with non-suppressed cycles. Jarvela et al. examined the effect of pituitary down-regulation in 40 women on ovarian volume, follicle number, vascularity and echogenicity, as assessed by the mean gray value5. Data following a mean duration of pituitary suppression of 16 (range, 14–33) days were compared with those derived from pre-treatment sonography conducted in the late follicular phase between days 8 and 16 of the menstrual cycle. The only consistent significant changes were a reduction in volume of the dominant ovary and an associated increase in the mean gray value in keeping with loss of the dominant follicle. Somewhat surprisingly, there were no differences in the three-dimensional indices of vascularity in either the dominant or the non-dominant ovary, despite the observed differences in volume and grayness. A significant reduction in the number of follicles was observed overall, but this was restricted to those ovaries with a polycystic appearance and the follicular diameters were not taken into consideration. The authors did not test the ability of ovarian volume or vascularity to define successful down-regulation and no data on eventual outcome were given. These issues are potentially important, as evident in the three-dimensional work focusing upon ovarian response. The dose and duration of FSH treatment is dependent upon each individual patient's response to stimulation and is adjusted dynamically during treatment dependent on the number of follicles developing and on the amount of estrogen they produce collectively as measured in the serum. The response and eventual number of mature oocytes retrieved is referred to as the patient's ‘ovarian reserve’. Prediction of ovarian reserve has obvious importance as it allows treatment to be tailored to the individual, potentially increasing the number of oocytes retrieved in those with a low reserve who need increased doses of FSH. This, however, must be balanced against inducing an over-response, which in extreme circumstances may lead to ovarian hyperstimulation syndrome, a serious and significant cause of morbidity and even mortality. The majority of reproductive medicine units adopt a standard approach to this based on age and a measurement of FSH during the early follicular phase in the 6 months prior to treatment. Patients in their twenties are usually offered two ampules of FSH (150 IU), those over forty are started on four ampules (300 IU), and the remainder receive three ampules (225 IU). These doses may be increased in those women with a pre-treatment FSH level above 10 IU/L, or reduced if the patient is thought to have polycystic ovarian syndrome, which is associated with a significantly greater chance of ovarian hyperstimulation syndrome. Accepting the expected reduction in ovarian reserve with age, patients generally respond in a similar fashion during subsequent treatment cycles and this may be used to modify protocols accordingly in those with prior aberrant responses. However, a certain degree of intrasubject variability occurs and a significant number of patients do not have previous treatment cycles to facilitate such comparison. The possibility of being able to predict outcome or ovarian reserve has attracted a great deal of attention and several potential markers have been suggested including those derivable from ultrasound data. Of the ultrasound markers suggested as predictive of ovarian response, the three that have been specifically addressed by three-dimensional ultrasound studies are ovarian volume, antral follicle counts and ovarian blood flow. Schild et al. examined the role of ovarian volume measurements made prior to ovarian stimulation but after down-regulation in 152 IVF cycles6. Ovarian volume did not correlate with IVF outcome and they were surprised to note a non-significant trend towards smaller ovarian measurements in the conception group. Subgroup analysis comparing absolute ovarian size revealed a pregnancy rate of only 6.7% (1/15) in patients with a minimum unilateral ovarian volume of ≤ 3 cm3, which represented a single standard deviation below the mean, vs. 21.9% (30/137) in patients with an initial minimum ovarian volume > 3 cm3. This difference was not significant, however, and cancellation rates due to poor ovarian response or failed fertilization were similar in both groups. Pellicer et al. also found no role for ovarian volume measurements as an adjunct to conventional markers of ovarian reserve in a group of ‘low responders’ in one of the first studies to use three-dimensional ultrasound7. Ten women defined as low responders, having developed no more than three follicles in two previous standard treatment cycles, were compared with eight control patients who had developed seven or more follicles previously, on day 3 of the menstrual cycle. In both groups all women were under the age of 35 with normal basal serum FSH levels. Whilst ovarian volume measurements were similar between the two groups, the number of ‘selectable follicles’ measuring 2–5 mm and the total number of antral follicles were significantly decreased in the low responder group, who also demonstrated significantly higher serum FSH levels despite having values within the normal range. Whilst the number of selectable follicles appears to be a potential discriminator of women with an impaired ovarian reserve, it is not possible to conclude from this study whether three-dimensional imaging offers any significant advantage over conventional ultrasound, as all follicle counts were conducted using the multiplanar display specific to three-dimensional ultrasound. Dumesic et al. found early follicular phase antral follicle counts not only to be superior to ovarian volume measurements in predicting ovarian response to FSH but also to be linked to androgen and insulin release8. In 25 ‘normal’ ovulatory women, both pre-treatment antral follicle count and serum androstenedione were positively correlated with subsequent total and mature oocyte numbers, whilst FSH, LH, inhibin A and B, testosterone, dehydroepiandrosterone sulfate, estradiol and total ovarian volume were unrelated to either. Insulin release in response to a standard oral glucose tolerance test (OGTT) was negatively correlated with total oocyte number but unrelated to mature oocyte number after controlling for antral follicle number. The antral follicle count, however, remained significantly correlated with mature oocyte number after controlling for post-OGTT insulin release, again demonstrating its independent power of prediction. Pellicer et al. defined ‘selectable follicles’ as those measuring 2 to 5 mm7, as it is at this stage that they become increasingly responsive to gonadotropins9. Pre-antral follicles measuring 0.15 mm take approximately 70 days to reach a size of 2 mm and during this time they remain relatively unresponsive to the cyclical changes in FSH and LH, demonstrating minimal granulosa cell proliferation and low steroidogenic activity. During the normal menstrual cycle the follicle destined to ovulate is recruited during the luteal phase of the preceding cycle from a pool of 3–11 antral follicles per ovary and is selected during the early follicular phase of the subsequent cycle10. With the exception of this dominant follicle, all healthy follicles are invariably 6 mm or less and many larger follicles are indeed atretic11. The relative proportion of follicles of different diameters may therefore also be an important determinant of response and outcome. Pohl et al. used three-dimensional ultrasound to quantify the number of follicles of various diameters in 113 patients following down-regulation and prior to ovarian stimulation12. Patients with a higher number of follicles measuring between 5 and 10 mm were younger (P < 0.01), had a significantly higher number of oocytes retrieved (P < 0.001) and were more likely to conceive (P < 0.05). A significant correlation was noted between follicle size and serum estradiol level in follicles measuring 11 mm or more (P < 0.05), and patients with follicles predominantly larger than 11 mm were more likely to have treatment cancelled due to a poor ovarian response. There is no doubt, therefore, that antral follicle counts and their relative diameters are important predictors of ovarian reserve and they may be measured with an acceptably high level of agreement both between and within observers. Three-dimensional ultrasound, however, has not been shown to offer any significant advantage over two-dimensional imaging in determining the number of antral follicles even at higher counts when interobserver reliability is reduced13. If we accept that three-dimensional assessment of ovarian volume and antral follicle count offers no significant advantage over conventional assessment, then the only other parameter to support a role for three-dimensional ultrasound is the assessment of vascularity through the quantification of the power Doppler signal. Jarvela et al. used three-dimensional power Doppler angiography to compare ovarian vascularity in 33 women with normal ovarian reserve, defined as the presence of five or more follicles measuring 2–5 mm, with 12 women with fewer than five such sized follicles14. Patients were examined after pituitary down-regulation and during gonadotropin stimulation. The number of oocytes retrieved correlated with the antral follicle count (R = 0.458, P < 0.01) and ovarian volume (R = 0.388, P < 0.05), but not with ovarian vascularity. However, whilst all three indices of vascularity were shown to increase significantly during gonadotropin stimulation in the group with normal ovarian reserve, this was not observed in the low responders. The increase in the ovarian power Doppler signal during gonadotropin stimulation was related to the antral follicle count, however, reinforcing the importance of this marker as an independent variable. Kupesic and Kurjak also demonstrated that the antral follicle count is a better predictor of response than are ovarian volume or vascularity in their study of 56 women with normal basal serum FSH concentrations undergoing their first cycle of IVF15. Whilst several factors were found to be significant, including the ovarian stromal flow index, peak estradiol on the day of hCG administration, total ovarian volume, total ovarian stromal area and age, the best predictor was total antral follicle number. When combined, these six parameters were able to predict a favorable outcome in 50% (11/22) of patients and a poor outcome in 85% (29/34) of patients. In a subsequent publication, ovarian volume, total follicle number and stromal vascularity were all shown to decrease with advancing age in the same group of patients16. However, within each individual age group the number of oocytes retrieved and the subsequent conception rate were greater in those patients with a greater ovarian volume, a higher number of antral follicles and more marked ovarian stromal vascularity. Whilst the value of three-dimensional ultrasound in predicting suboptimal ovarian response is limited, it may have a role in identifying those women who are prone to an exaggerated response. Pan et al. used three-dimensional ultrasound on the day of hCG administration to study patients demonstrating an exaggerated response to controlled ovarian stimulation, as defined by an estradiol level above 3000 pg/mL on the day of hCG administration or the retrieval of 15 oocytes or more17. Ovarian volume and vascularity were found to be significantly higher in 23 so called ‘hyper-responders’ compared with 35 normally responsive controls (volume, 48.48 ± 25.87 vs. 24.38 ± 9.68; vascularization index, 1.18 ± 0.60 vs. 0.63 ± 0.61; flow index, 50.23 ± 2.81 vs. 43.19 ± 7.81; vascularization flow index, 2.27 ± 1.08 vs. 1.25 ± 1.18). Further work is warranted but probably using a more generally agreed definition of ‘hyperstimulation’ in a larger patient population as the prevalence of overstimulation will be less. If patients susceptible to an over-response can be prospectively identified in a reliable manner and excluded, higher doses of FSH may be employed for standard ovarian stimulation protocols than are currently used in the remaining patients. Fertilization of an oocyte is confirmed by the presence of two pronuclei 18–24 h after IVF or ICSI. The embryos are allowed to develop in vitro until the second or third day after oocyte retrieval when most units would transfer to the recipient uterus a maximum of two embryos selected on the basis of their quality as determined by a subjective grading system. Embryos may, however, be cultured for up to 5 days and transferred at the blastocyst stage in the hope of achieving a higher implantation rate for every single embryo replaced. The chance of the implantation occurring is not only dependent upon the embryo's stage and grade but also on the endometrium. Just how important ‘endometrial receptivity’ is in the overall process remains uncertain, but the endometrium is likely to play more than a passive role18. This is substantiated by the fact that implantation is unlikely to occur in the presence of an endometrium measuring less than 5 mm in diameter19. Conception is not necessarily more likely in women with a thicker endometrium and therefore the role of endometrial thickness measurement is really restricted to its negative predictive value. Studies examining the role of three-dimensional ultrasound have compared measurements of endometrial volume and vascularity with thickness measurements as the current standard. Schild et al. compared endometrial thickness and endometrial volume in a total of 47 IVF cycles on the day of oocyte retrieval20. There were no significant differences between the group of 15 patients that conceived (31.9%) and the remaining 32 non-pregnant women in terms of the mean endometrial thickness (10.8 ± 2.3 mm vs. 11.8 ± 3.4 mm) or volume (4.9 ± 2.2 cm3 vs. 5.8 ± 3.4 cm3). In keeping with the current evidence there was a wide range of endometrial thickness measurements in both pregnant patients (6.9–16.0 mm) and non-pregnant patients (6.5–21.1 mm), and no obvious correlation between estradiol concentrations and endometrial thickness or volume. Yaman et al. reported similar findings with no differences in endometrial volume (4.16 ± 1.97 cm3 vs. 4.53 ± 1.79 cm3), endometrial thickness (11 ± 2 mm vs. 11 ± 2 mm) or serum estradiol (1686 ± 1057 pg/mL vs. 1883 ± 1147 pg/mL) between 21 pregnant and 44 non-pregnant women on the day of hCG administration21. However, whilst there was no absolute endometrial thickness required for pregnancy a minimum endometrial volume above 2.5 cm3 favored pregnancy. Raga et al. also described a cut-off point in endometrial volume in their study of 72 patients on the day of embryo transfer22: Implantation rates were significantly lower (P < 0.05) in those women with an endometrium measuring less than 2 cm3 and no pregnancies were observed at volumes below 1 cm3. volume measurement would to offer a and negative predictive value to endometrial thickness in predicting implantation after embryo transfer therefore upon its sensitivity in the Kupesic et al. reported that more predictive be derived at the time of embryo transfer when three-dimensional power Doppler was used to quantify endometrial In successful conception cycles were associated with a significantly higher endometrial flow ± 2.2 vs. ± P < 0.05). This study the from three-dimensional blood flow analysis as assessment of endometrial thickness and volume or in combination with Doppler findings in the of a offered any power in the of successful cycles. et al. found three-dimensional power Doppler angiography to be an important determinant of endometrial on the day of hCG administration in patients undergoing their first IVF The vascularization flow proved the best predictor of being superior to the vascularization index, flow and endometrial volume in ROC curve the only study not to any from three-dimensional power Doppler in determining the of the endometrium was that of et in which the power Doppler signal was through of the on the day of oocyte retrieval in patients undergoing IVF all indices of blood flow were significantly higher during the but this did not into any in terms of identifying those women with successful cycles. were relatively however, and this approach assessment, not only in terms of the absolute quantification of power Doppler but also through the of and the of the signal following a of as this is the more to examine Three-dimensional assessment of endometrial vascularity may even be used to predict endometrial and eventual outcome prior to ovarian stimulation. Schild et al. used three-dimensional power Doppler angiography to examine the area at the of down-regulation and prior to ovarian stimulation in IVF patients conceived and in these women all three indices of vascularity were significantly lower than they were in cycles (P < 0.05) with the flow being the predictive of (P < 0.05). measurements again were not correlated with outcome. These findings may a more pituitary suppression in those that conceive but are more likely to to patients that respond more to down-regulation are more likely to respond to FSH stimulation, an effect that be through different of expression within the hypothalamic–pituitary–ovarian This study was also in that it was the first to examine blood defined as the within 5 mm of the This was through the of the which the within an three-dimensional the of the and the fact that the endometrial is more than it is that this proved reliable and revealed such significant that vascularity did between the groups. If we accept that three-dimensional analysis of endometrial vascularity and endometrial volume do have a role in determining endometrial then we must how such may be used to implantation and cycle would be to a in which treatment, embryo was based upon measurement of endometrial volume or endometrial thickness. If conception were unlikely to occur below certain then the transfer of embryos be and all potentially embryos for use in subsequent embryo cycles. However, the rate of such treatment remains below that for the transfer of A study examining outcome based upon the cancellation of embryo transfer cycles dependent on measurements of endometrial volume and vascularity in with conventional markers would be more but this has for the or the possibility is to the dose or duration of ovarian stimulation, or to endometrial through the administration of have been including and A significant number of studies have been to examine the value of and blood flow measurements specific to three-dimensional ultrasound in assisted reproduction treatment. of these studies are and therefore but they do offer into how this imaging may be used to outcome for patients undergoing treatment. studies are indeed essential following the of any new as they for other to their studies and ensure the of new Ovarian volume measurements do not to offer any advantage over similar measurements derived from two-dimensional data and stromal blood flow is less in ovarian response compared with antral follicle However, the through the quantification of the power Doppler signal within the endometrium and to significantly between cycles and conception cycles and between the various of treatment. to three-dimensional ultrasound for evidence of above that of current but this can only be by do not accept that of three-dimensional imaging are for its but to that they its potential and to its in to the of patients. is essential, therefore, that work in this area is and that any findings are prospectively in controlled","author":[{"@type":"Person","name":"Nick Raine‐Fenning","url":"https://synapsesocial.com/authors/A5063859688"}],"isPartOf":{"@type":"Periodical","name":"Ultrasound in Obstetrics and Gynecology","url":"https://synapsesocial.com/journals/6896392638e66137c4353196"},"publisher":{"@type":"Periodical","name":"Ultrasound in Obstetrics and Gynecology","url":"https://synapsesocial.com/journals/6896392638e66137c4353196"},"sourceOrganization":[{"@type":"Organization","name":"Queen's Medical Centre","url":"https://synapsesocial.com/institutions/68924f578807423d81a6e333"}],"isBasedOn":"https://doi.org/10.1002/uog.1028","identifier":[{"@type":"PropertyValue","propertyID":"DOI","value":"10.1002/uog.1028"},{"@type":"PropertyValue","propertyID":"OpenAlex","value":"https://openalex.org/W2017764393"}],"sameAs":["https://doi.org/10.1002/uog.1028","https://openalex.org/https://openalex.org/W2017764393"],"citationCount":18},{"@type":"MedicalWebPage","@id":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e#webpage","url":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e","name":"The role of three‐dimensional ultrasound in assisted reproduction treatment","about":{"@id":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e#article"},"mainContentOfPage":{"@id":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e#article"},"medicalAudience":[{"@type":"MedicalAudience","audienceType":"Clinician"},{"@type":"MedicalAudience","audienceType":"Researcher"}],"inLanguage":"en","isPartOf":{"@type":"WebSite","@id":"https://synapsesocial.com#website","url":"https://synapsesocial.com","name":"Synapse"},"lastReviewed":"Fri, 10 Oct 2025 00:00:00 GMT"},{"@type":"BreadcrumbList","@id":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e#breadcrumbs","itemListElement":[{"@type":"ListItem","position":1,"name":"Synapse","item":"https://synapsesocial.com"},{"@type":"ListItem","position":2,"name":"Explore","item":"https://synapsesocial.com/explore"},{"@type":"ListItem","position":3,"name":"The role of three‐dimensional ultrasound in assisted reproduction treatment","item":"https://synapsesocial.com/papers/6a976b9804c78a31a48bd89e"}]}]}

The role of three‐dimensional ultrasound in assisted reproduction treatment

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The role of three‐dimensional ultrasound in assisted reproduction treatment

Discussion

Member takes

Implication

Key Points

Cite This Study