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Section 3
Chapter
24
Ultrasonography in assisted reproduction
Ultrasonography and IVF
Luciano G. Nardo and Tarek A. Gelbaya
Introduction
The availability of a good ultrasonography (US) service as part
of clinical in-vitro fertilization (IVF) is of paramount importance. Over the last 25 years, progress in the field of assisted
reproduction has paralleled that in ultrasonography. During
the initial IVF attempts, follicular growth was monitored by
measurement of urinary estrogen and plasma luteinizing hormone (LH) concentrations. The correlation between follicular
size and urinary estrogen concentrations was poor, as many
small follicles producing significant amount of estradiol (E
could not be measured by US. Hackelöer and Robinson [1] were
the first to report successful monitoring of follicular size and
number in patients undergoing ovulation induction using a
transabdominal static B-scan. In 1982, O’Herlihy and coworkers published on the follicular size criteria and protocols
for ovulation induction [2].
Oocyte retrieval started as a laparoscopic procedure until
Lenz and colleagues described percutaneous transabdominal/
transvesical aspiration of ovarian follicles in 1981. They demonstrated for the first time that oocyte retrieval could be performed as an ultrasound-guided outpatient procedure [ 3]. In
1983, transvaginal oocyte retrieval under transabdominal ultrasound (TAS) guidance was further described by Gleicher and
collaborators [4]. The true impact on ovum pick-up came with
the appearance of the mechanical transvaginal sector scanner,
when Kemeter and Feichtinger described its use for transvaginal aspiration of ovarian follicles in IVF [5]. In the late 1980s,
the greatest development of transvaginal imaging was in human
assisted reproduction. In this field, both diagnostic and therapeutic approaches require the use of transvaginal ultrasonography (TVS), including the initial assessment of subfertile
women for pelvic pathologies, surveillance of ovarian follicles
and endometrial responses with or without medications, oocyte
retrieval, embryo transfer, and diagnosis of clinical pregnancy.
Transvaginal and transabdominal approaches
The pelvic organs may be imaged using transabdominal or
transvaginal ultrasonography. The transabdominal approach
requires a full bladder in order to displace the bowel and
provide an acoustic window through which pelvic organs can
be visualized. Transvaginal ultrasound has become the method
of choice for pelvic assessment and management of subfertile
women. Nevertheless, TAS may be necessary for adequate visualization of pelvic-abdominal masses, enlarged uterus, or high
(abdominal) ovaries. The elasticity of the vaginal wall and the
close proximity of the vaginal probe to the pelvic structures
allow the use of high-frequency ultrasound waves with short
focal length, giving enhanced resolution compared with TAS.
)
2
Care must be taken to minimize the risk of cross-infection by
cleaning the probe thoroughly, changing the protective sheath
after every examination, and using sterile sachets of gel. Current
evidence does not suggest any adverse effects of ultrasound on
the oocytes, embryos, or early pregnancy [6].
Initial investigations of the subfertile woman
Transvaginal ultrasound can be used to rule out pelvic pathology in subfertile women who suffer from other symptoms such
as dysmenorrhea, chronic pelvic pain, deep dyspareunia,
hirsutism, and/or menstrual disorders. In addition, TVS can
be used in the evaluation and follow-up of women with known
pelvic pathology, such as endometriosis, endometrial polyps,
leiomyoma, uterine anomalies, and adnexal pathology.
Although TVS is not a prerequisite for referring a couple for
assisted conception, it enables accurate evaluation of pelvic
anatomy and helps to reassure women, especially those with
idiopathic subfertility.
Ultrasound of the uterus
The uterus is usually easily identifiable with its uniformly
reflective myometrium and the midline endometrial echo.
The appearance of the endometrium varies throughout the
menstrual cycle, being very thin immediately after menstruation, thickening and becoming more prominent during the
proliferative phase, assuming the trilaminar appearance before
ovulation, and being thick and reflective in the secretory phase
of the cycle. Figure 24.1 shows the typical appearance of the
Ultrasonography in Reproductive Medicine and Infertility, ed. Botros R. M. B. Rizk. Published by Cambridge University Press. © Cambridge
University Press 2010.
Section 3: Ultransonography in assisted reproduction
Figure 24.1. Trilaminar preovulatory endometrium.
preovulatory endometrium. A trace of endometrial fluid may
normally be seen at the time of ovulation, leading to a slight
separation of the endometrial layers, but this fluid usually
disappears within 24 hours. The endometrial growth in stimulated cycles is very similar to that in the natural cycle, despite
higher serum estradiol levels.
Leiomyoma
Fibroids may be identified by disruption of either the uniform
myometrial reflectivity or the smooth uterine outline. They
often contain highly reflective regions that will lead to acoustic
shadowing. Very large fibroids are best seen with TAS as they
often extend beyond the effective range of the transvaginal
probe. The relationship of the fibroids to the uterine cavity is
better examined by TVS. The effect of fibroids on fertility
depends on the location and size of the fibroid, with large
myomas indenting the endometrium having greater impact
on fertility performance and pregnancy outcome [7].
Endometrial polyps
With the advent of TVS, saline sonohysterography, and
improved Doppler techn ology the ultrasonographic diagnosis
of endometrial polyps has become highly accurate [8].
Endometrial polyps are often seen on days 2–3ofthebaseline
TVS as a demarcated lesion with di ffe rent echogenicity within
the endometrial cavity. Many authors advise hysteroscopy and
removal of the polyp before ovarian stimulation is commenced for IVF. This is particularly the case with polyps of
1 cm diameter or more. Stamatellos and co-authors reported
no differences in pregnancy and miscarriage rates between
women with small polyps (≤1 cm) and those with large or
multiple polyps [9]. Saline infusion sonohysterograpy (SIS)
canimprovethediagnosticaccuracyfordetectionofanendometrial polyp. The presence of thick endometrium on day 2 or
3 of the menstrual cycle should raise the possibility of a local
endometrial lesion, and hysteroscopy should be considered in
such cases.
Endometrial fluid
The ultrasound visualization of fluid in the endometrial cavity
before embryo transfer in IVF cycles is associated with poor
prognosis. The fluid may be cervical mucus that ascends into
the endometrial cavity, but it may also be associated with fluid
reflux from a hydrosalpinx [10] or subclinical uterine infection
[11] or may be the result of abnormal endometrial development
[12]. The identification of persistent fluid accumulation may
prompt the clinician to freeze all embryos and postpone the
embryo transfer.
Assessment of endometrial and uterine contour
Although there is a debate about the role of endometrial texture
in implantation, endometrial contour is less disputed.
Endometrial abnormalities such as fibroids and septa can
cause implantation failure. The diagnosis of “double uterus”
has traditionally been achieved through hysterosalpingography
(HSG). However, this technique cannot differentiate between a
unified corpus with a septum and a bicornuate uterus, nor
between a complete septate and a didelphic uterus. Although
some authors claim there are hysterographic criteria that can
distinguish the various uterine malformations, it is currently
accepted that accurate diagnosis requires knowledge of the
morphology of the peritoneal surface of the uterine fundus.
Hysteroscopy alone cannot provide an accurate diagnosis, and
laparoscopy is required in order to assess the peritoneal configuration of the uterine fundus.
Accurate visualization of the fundus can be obtained by TVS
with a sensitivity of 100% and a specificity of 80% [13]. A
septate uterus on TVS is represented by a convex, flat and
minimally indented (<1 cm) fundal contour with an echogenic
structure dividing the cavity. Saline infusion sonohysterography may improve the information obtained by ultrasonography
alone. Three-dimensional ultrasound seems to constitute a
valid alternative to traditional ultrasound, showing a sensitivity
and specificity close to 100% [14]. Uterine anomalies can be
associated with congenital anomalies of the urinary tract; hence
imaging of the urinary tract with appropriate techniques should
be performed.
Ultrasound of the fallopian tubes
Normal fallopian tubes are not usually seen by ultrasound,
though it is sometimes possible to visualize the fimbrial end
within fluid in the pouch of Douglas.
Hydrosalpinx
Hydrosalpinges are easily identified by TVS (Figure 24.2).
Typically the distended tube is coiled around the ovary in a
sausage-shaped appearance. The presence of a hydrosalpinx
adversely aff ects implantation and pregnancy rates. Two
meta-analyses demonstrated a reduction by half in the probability of achieving a pregnancy in the presence of hydrosalpinx
and a doubled rate of miscarriage [15,16]. TVS is useful
in identifying the coexistence of periadnexal adhesions in
194
Chapter 24: Ultrasonography and IVF
Figure 24.3. Uterus and ovaries.
Figure 24.2. Hydrosalpinx.
women with hydrosalpinx. In these cases, the typical ultrasound
appearance of a hydrosalpinx is associated with “loss of sliding
signs” during the transvaginal examination. In subfertile
women with dense pelvic adhesions, laparoscopic proximal
division of the damaged fallopian tube(s) is an effective alternative to salpingectomy for hydrosalpinx prior to IVF [17].
Ultrasound for tubal patency
Different tests exist to investigate tubal patency in women
seeking fertility. The most common diagnostics includ e laparoscopy and dye test, HSG, and hysterosalpingo-contrast sonography (HyCoSy). The advantage of HyCoSy is that it allows for
concomitant ultrasound assessment of the ovaries and the
uterus. In addition, it is well tolerated by women and provides
an effective outpatient alternative to hysterosalpingography or
laparoscopy and dye test [18].
Ultrasonography of the ovaries
The ovaries are usually seen lateral to the uterus (Figure 24.3),
in close relationship to the internal iliac vessels. They can be
identified by their echogenic stroma and sonolucent follicles.
Occasionally, they may be located behind or above the uterus or
under the anterior abdominal wall. A high ovary may be
brought into the field of the view of the transvaginal probe by
pressing firmly on the lower abdomen. The ovary tends to be of
slightly lower reflectivity than the uterus, with low-level echoes
surrounding the follicles. The ovarian volume can be estimated
using the approximate formula: volume = length × width ×
depth × 0.5. The nonstimulated ovary in women with regular
cycles has a mean volume of 9.8 ml [19].
that PCOS could be diagnosed by having two of the following
three features, after the exc lusion of related disorders: (1) oligoovulation or anovulation; (2) clinical and/or biochemical signs
of hyperandrogenism; or (3) polycystic ovaries [20 ].
Ultrasound criteria for polycystic ovaries (PCO) were defined
as the presence of 12 or more small follicles in each ovary
measuring 2–9 mm in diameter and/or increased ovarian volume of more than 10 ml. The follicle distribution and stromal
echogenicity and volume were omitted from the ultrasound
features. Only one ovary fitting this definition is sufficient for
the diagnosis of PCO. If there is a follicle more than 10 mm in
diameter or a corpus luteum, the ultrasound should be repeated
during the next cycle. The definition does not apply to women
taking the oral contraceptive pill, since its use modifies the
ultrasound morphology of the ovary [20].
Functional ovarian cysts
The normal follicle typically reaches a maximum diameter of
22–25 mm at ovulation, following which it shrinks or disappears gradually. Failure of the follicle to rupture may cause a
follicular cyst. Luteal cysts result from failure of involution of
the corpus luteum. Follicular and luteal cysts are characterized
by echo-free contents, usually measuring less than 5 cm in
diameter with a smooth outline. Most simple ovarian cysts in
women of reproductive age are functional and will resolve
spontaneously. If the cyst persists it may be aspirated transvaginally, and only if it recurs is cystectomy required. An
irregular margin in a persistent cyst is an indication for cystectomy, though this is uncommon in young women seeking
fertility treatment. Blood-filled ovarian cysts may be identified
by internal echoes in the form of septa or gravity-dependent
particulate debris.
Ultrasound and polycystic ovary
Ultrasound is important, but not essential, in the diagnosis of
polycystic ovary syndrome (PCOS). The Rotterdam consensus
meeting sponsored by the European Society for Human
Reproduction and Embryology (ESHRE) and the American
Society for Reproductive Medicine (ASRM) in 2003 stated
Endometrioma
Endometrioma is an ovarian mass arising from growth of
ectopic endometrial tissue in the ovary. Endometrioma may
vary in size from 1 cm to a large, complex mass that occasionally may be difficult to differentiate from an ovarian neoplasm.
Endometriomas contain thick, altered blood that typically
195
Section 3: Ultransonography in assisted reproduction
Figure 24.4. Endometrioma.
generates numerous low-level echoes (Figure 24.4). Of note,
endometriomas that are not adjacent to clear fluid-containing
cystic structures may be difficult to differentiate from ovarian
stroma. However, by the use of pattern recognition, TVS can
confidently diagnose 80% of endometriomas [21].
Dermoid cysts
Dermoid cysts may occasionally be identified in the ovaries of
women of reproductive age. They can be cystic, solid, or complex depending on the components. The classic appearance is a
well-circumscribed mass containing a fluid-debris level with a
highly reflective internal echo, which produces acoustic
shadow. Hair floating on sebum is strongly reflective and may
cause shadow distally, obscuring the deeper tissues. In this case,
only the anterior margin of the dermoid will be visualized,
giving rise to the “tip of the iceberg” sign in which most of
the volume of the mass is not seen.
Assessment of ovarian reserve
A variety of ovarian reserve tests are used in routine clinical
practice to assess a woman’s ovarian performance prior to
controlled ovarian hyperstimulation (COH) for IVF. These
include measurement of day 2 serum FSH, E
hormone (AMH), inhibin-B, and antral follicle count (AFC).
Follicular growth is a continuous process, independent of
gonadotropin stimulation until the follicles reach 5 mm in
diameter. Further growth of the follicles requires appropriate
gonadotropin stimulation. Follicles measuring 2–5 mm (antral
follicles) are seen by TVS in the early follicular phase of the
menstrual cycle, and they normally develop under the influence
of pituitary hormones as the cycle progresses. It has been
reported that the number of antral follicles correlates well
with the woman’s age, ovarian reserve, and ovarian response
to gonadotropin stimulation. There is a continuous and rapid
loss of follicles due to apoptosis over the woman’s reproductive
life; and as the ovary ages, there is a noticeable reduction in the
, antimüllerian
2
ovarian volume and the number of antral follicles. The AFC is
regarded as a relatively good marker to predict poor ovarian
response in assisted reproduction programs, providing better
information than the patient’s age alone or several endocrine
markers [22]. The test can obviously be done at the time of the
baseline ultrasound scan before commencing ovarian stimulation, thus avoiding repeat ultrasound scans. An AFC less than 6
correlates well with reduced ovarian reserve and poor response
to ovarian stimulation, with a positive predictive value of
75% [23].
Monitoring ovarian response to gonadotropin stimulation
Ultrasound assessment of follicular growth was first introduced
in 1978 when Hackelöer and Robinson [1] described a linear
relationship between follicle size and circulating E
then, TVS has been used to routinely monitor follicular growth
in natural cycles, in ovulation induction programs, and during
COH for assisted reproductive technology cycles.
During the natural cycle, a cohort of small antral follicles
(2–5 mm in diameter) appears in the ovary very early in the
proliferative phase. As FSH levels rise, further growth of the
follicles occurs and the decline of FSH in the late follicular
phase allows the selection of the single most sensitive follicle
to continue to develop. Once the leading follicle reaches a
diameter of approximately 14mm, the daily growth rate is
between 1.5 and 2.0 mm until reaching a diameter of 22–
25 mm, when ovulation occurs. In natural cycles, serum E
levels correlate with follicle size, while the contribution of
small atretic follicles to the steroidal milieu is negligible.
Characteristic ultrasound appearance at the time of ovulation
includes diminution in the follicle size, blurring of the follicle
borders, and appearance of intrafollicular echoes and presence
of a small amount of free fluid in the pouch of Douglas.
Thereafter, an irregular, slightly cystic structure representing
the corpus luteum shrinks throughout the luteal phase of the
cycle until luteolysis occurs before menses.
Ultrasound scanning is useful in monitoring the response
to clomiphene citrate in anovulatory women. TVS is usually
performed 4–5 days after the last dose of clomiphene and every
2–3 days until a follicle of approximately 20 mm in diameter is
seen.
Ovulation induction with gonadotropins overcomes the
normal feedback mechanism that allows for physiological unifollicular ovulation causing growth of a cohort of follicles at
various stages of development (Figure 24.5). To ensure safe
clinical practice, a maximum of two leading follicles per cycle
should be present. As the risk of ovarian hyperstimulation
syndrome (OHSS) and multiple pregnancies is significant, it is
important to monitor treatment response carefully by serial
ultrasound scans and serum E
cycle, the linear relationship between follicle size and E
urements is lost due to the presence of many developing follicles
that contribute to the circulating E
cycles, a baseline ultrasound scan is performed to exclude
levels. In contrast to a natural
2
. In ovulation induction
2
levels. Since
2
meas-
2
2
196
Figure 24.5. Follicles of various sizes after ovulation induction.
functional ovarian cysts, as well as other pelvic pathologies.
Monitoring is usually carried out using TVS on day 8 of treatment. The dose of exogenous gonadotropins is adjusted according to the response. If more than two leading follicles (>17 mm)
are seen, human chorionic gonadotropin (hCG) should be
withheld and the cycle canceled to avoid the risk of multiple
pregnancies.
Follicular size is best estimated by calculating the mean of
the maximum follicular diameter in three planes. The interobserver variation in measurement is larger than the intraobserver
variation, with the least interobserver variation being ±1.6 mm
using TVS. This suggests that follicular tracking is more accurate when each scan is performed by the same operator [24]. In
the presence of several follicles, the measurement of the largest
four follicles in each ovary and a count of the remaining smaller
follicles is considered as satisfactory. Follicular growth of
approximately 2–3 mm per day is expected under normal
circumstances.
Follicles can occasionally be confused with other pelvic
structures, but they can be differentiated by rotating the transducer 90°. If the structure is a vessel, it will then elongate,
acquiring a tubular shape. The internal iliac artery can easily
be identified by its arterial pulsations, while a hydrosalpinx
generally has a less regular shape (Figure 24.2).
Monitoring of the ovarian response in COH cycles can be
carried out by TVS alone. Starting from day 8 of stimulation
and then every other day, the dimensions of the growing follicles are plotted on a chart. Provided the TVS is performed by
an experienced operator, daily measurements of serum E
2
concentrations may have limited value in predicting the success of
the cycle or the risk of OHSS [25]. When FSH alone is used for
ovarian stimulation in long protocols, the serum E
concentra-
2
tion is approximately half of the level found when human
menopausal gonadotropins (hMG) is used. As serum E
2
concentrations appear to be proportional to the amount of LH in
the gonadotropin preparation used in the stimulation regimen,
the findings may be misleading.
Chapter 24: Ultrasonography and IVF
Ultrasound assessment of the endometrium
The endometrium undergoes cyclic morphological as well as
histological changes throughout the menstrual cycle. During
menstruation, the endometrium appears as a thin echo that
gradually thickens throughout the proliferative phas e to reach
the typical periovulatory trilaminar appearance (Figure 24.1).
After ovulation, the rise in circulating progesterone induces
stromal edema and growth of spiral arterioles, resulting in
increased echogenicity of the thick secretory endometrium.
Ultrasound assessment of the endometrium has received a
great deal of attention in the analysis of factors that affect
embryo implantation. The literature has shown conflicting
evidence about the predictive value of ultrasonography in the
assessment of implantation failure and pregnancy potential.
Several investigators have reported no difference in endometrial thickness between pregnant and nonpregnant women
[26,27], while others have observed a positive correlation
between endometrial thickness and pregnancy outcome
[28,29]. Zhang and co-authors found that increased endometrial thickness was associated with improved treatment outcome, but the association was dependent on patient age,
duration of ovarian stimulation, and embryo quality [30].
Conversely, Richter and colleagues concluded that the higher
clinical pregnancy and live-birth rates associated with increasing endometrial thickness were independent of the effects of
patient age and embryo quality [31]. A meta-analysis of the
literature demonstrated that endometrial thickness is a better
negative than positive predictor of implantation [32 ]. Studies in
the literature have proposed different endometrial thickness
cut-off levels for successful implantation to occur: ≥6mm
[26], ≥10 mm [29], and ≥13mm [33]. There have been no
reports of adverse effects of a thickened endometrium on
implantation, pregnancy, or miscarriage rates in IVF [34].
Endometrial echogenic patterns have also been studied. An
association has been shown between the ultrasound endometrial texture and serum hormonal levels [33]. In IVF cycles, a
preovulatory, multilayered appearance of the endometrial echo
has been associated with a positive pregnancy outcome when
compared with an incomplete, echogenic, and homogeneous
pattern [26,33,35]. Synchronization between endometrial and
embryo development is an essential prerequisite for successful
implantation.
The endometrial thickness and pattern may provide useful
information in cycles in which the endometrium is supplemented with estrogen and progesterone, such as in downregulated frozen embryo transfer cycles as well as in recipients
of donated oocytes or embryos. A minimal endometrial thickness of 6 mm is required before embryo replacement for pregnancy is achieved in oocyte recipients’ cycles [36,37]. In a
recent retrospective analysis of medicated frozen embryo
replacement (FER) cycles, an endometrial thickness of
9–14 mm on the day of progesterone supplementation was
found to be associated with higher implantation and pregnancy
rates compared with an endometrial thickness of 7–8mm [38].
In this study, the authors demonstrated that the lowest
197
Section 3: Ultransonography in assisted reproduction
Figure 24.6. Ovary during oocyte retrieval.
pregnancy rates were associated with endometrial thickness
<7 mm and >14mm.
Uterine artery blood flow
There have been conflicting reports in the literature regarding
the usefulness of the application of color Doppler ultrasound
for monitoring and predicting pregnancy outcome of IVF
cycles. Several studies used the pulsatility index (PI) as the
measure of impedance and determined that a PI of <3.0 [39]
or <3.34 [26] was more favorable for pregnancy. More recently,
Steer and co-authors found similar results in women undergoing frozen embryo transfer in a down-regulated hormonally
prepared cycle [40]. In contrast, other researchers found that
uterine artery PI did not significantly change until the midluteal phase. No difference was found in uterine or ovarian
artery PI between pregnant and nonpregnant women, but
there was a nonsignificant increase in uterine receptivity when
the uterin e artery PI was in the range of 2.0–2.99 on the day of
embryo transfer [41]. Other investigators used resistance index
(RI) and found that it was significantly lower at the time of
oocyte collection in women who achieved a pregnancy [35]. In a
recent study, Ng and colleagues performed 3D ultrasound
power Doppler one day after LH surge in women undergoing
frozen embryo transfer in natural or clomiphene-induced
cycles. The age of women was the only predictive factor for
pregnancy. Endometrial thickness, endometrial volume, endometrial pattern, uterine PI, uterine resistance index (RI), and
endometrial and subendometrial 3D power Doppler flow indices were similar between the nonpregnant and pregnant groups
[42]. Currently, measurement of uterine artery blood flow
should not be part of routine IVF practice.
Oocyte retrieval
Transvaginal ultrasound-guided aspiration of ovarian follicles
provides a safe and effective means of oocyte retrieval. It is
usually performed under sedation as a day-case procedure
and requires minimal postoperative analgesia. The needle
used for aspiration has a 17-gauge outer diameter and is
approximately 11 inches (27 cm) long. The tip of the needle is
Figure 24.7. Ovary after stimulation, before oocyte retrieval.
Figure 24.8. Ovary after oocyte retrieval.
echogenic, enabling visualization by ultrasound at all times
during the procedure (Figure 24.6). The needle is passed
through a guide that is fixed to the transducer, allowing for
proper alignment of the needle with the ultrasound beam. Care
should be taken to avoid damage to internal iliac vessels or
bowel by visualizing the needle tip at all times. Figures 24.7 and
24.8, respectively, show an ovary with three mature follicles
before oocyte retrieval and an ovary immediately after the
same procedure.
Ultrasound-guided embryo transfer
Embryo transfer is a crucial step of IVF treatment. It can be
performed with or without ultrasound guidance. Embryo transfer entai ls the delivery of the embryo(s) into the uterine cavity,
in a location where implantation is maximized. Embryo(s)
contained in the soft Teflon catheter are placed about 1.5 cm
from the fundus of the uterus.
The use of ultrasound guidance for embryo transfer was
first described by Strickler and colleagues in 1985 [43]. TAS has
198
been used to verify that the catheter has passed into the endometrial cavity and the embryo(s) has been transferred. Indeed,
ultrasound guidance has many potential advantages. It facilitates the passage of the catheter through the sharp cervicouterine angle, avoids touching the fundus, confirms that the
catheter is beyond the internal os in cases of elongated cervical
canal, and minimizes endometrial disruption. Molding of the
embryo transfer catheter according to the cervicouterine angle
measured by TAS has been associated with increased clinical
pregnancy and implantation rates [44]. Furthermore, in cases
of impossible transcervical embryo transfer, TVS-guided transmyometrial transfer can be an option, especially in women with
known tubal disease in whom intrafallopian transfer will not be
possible [45]. Ultrasound guidance is useful for trainees as it
enables them to master the technique of embryo transfer without compromising the success rate.
Whether ultrasound guidance improves clinical pregnancy
per embryo transfer is debatable, however. Two meta-analyses
reported higher pregnancy rates with ultrasound-guided embryo
transfer compared with non-ultrasound-guided embryo transfer
[46,47]. Conversely, a recent large random controlled trial concluded that TAS guidance during embryo transfer did not
improve clinical pregnancy and implantation rates provided
that the transfer was performed by an experienced operator
[48]. Of interest, in this trial patients were not required to have
a full bladder at the time of TVS-guided embryo transfer. Within
our department, the use of ultrasound-guided embryo transfer
has significantly improved implantation and clinical pregnancy
rates [49].
Chapter 24: Ultrasonography and IVF
Figure 24.9. Ovary with signs of excessive response to ovarian stimulation.
Complications of IVF
Ultrasound is a cornerstone of prevention and diagnosis of
potential IVF complications such as ovarian hyperstimulation
syndrome (OHSS) and multiple pregnancies.
Ovarian hyperstimulation syndrome
Measures to prevent OHSS remain the most desirable
approach. Management of OHSS is mostly expec tant, with a
small proportion of patients requiring hospitalization. The risk
of OHSS is significantly increased in women with an ultrasound
feature of PCO (odds ratio of 6.8, 95% confidence interval 4.9–
9.6) [50]. The excessive ovarian response to stimulation with
exogenous gonadotropin in women with PCO can be explained
by the large pool of small antral follicles available for recruitment [51]. The initial dose of gonadotropins can be adjusted
according to the appearance of the ovaries at the time of baseline ultrasound scan rather than to the diagnosis of PCOS.
Monitoring of follicular size and number during COH is
essential for prevention of OHSS. A correlation between OHSS
and the number of intermediate-sized follicles has been
reported [52]. A combination of ultrasound monitoring of
follicular growth/number and serial measurement of serum E
is used routinely in IVF to enhance the prediction rate of OHSS.
Women who develop more than 20 follicles in both ovaries,
with the majority being small (less than 14 mm in diameter), or
Figure 24.10. Free fluid in the pouch of Douglas
those who have high serum E
higher risk of OHSS. It is beyond the scope of this chapter to
discuss strategies used to reduce the risk of OHSS.
Figure 24.9 shows an ovary with several follicles, which is in
keeping with excessive response to stimulation. Figure 24.10
shows free fluid in the pouch of Douglas in a case of OHSS.
levels (>10 000 pmol/l) are at
2
Early pregnancy complications and multiple pregnancies
Ultrasound is essential for the diagnosis of clinical pregnancy,
confirmation of viability, dating of pregnancy, and diagnosis
of ectopic and multiple pregnancies. In the UK, despite the
policy of transferring no more than two embryos, the risk of
multiple pregnancy remains high at approximately 20–25%.
2
Information of a twin pregnancy in early gestation is important
for counseling as well as management of potential complications and antenatal care.
199
Section 3: Ultransonography in assisted reproduction
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201
Chapter
Ultrasonography and hydrosalpinges in IVF
25
Annika Strandell and Seth Granberg
Background
In the beginning of the in-vitro fertilization (IVF) era, tubal
factor infertility was the sole indication for the treatment.
Today, other indications constitute the majority of treatments
and tubal disease may account for as little as 20% in some IVF
centers. It is notable that tubal factor infertility is often reported
to yield worse results than other causes of infertility.
Hydrosalpinx is a severe condition that has attracted special
interest in research and clinical practice. Hydrosalpinx is a
commonly used term to describe a heterogeneous spectrum of
pathology of distal tubal occlusion. A strict definition is a
collection of watery fluid in the uterine tube, occurri ng as the
end stage of pyosalpinx. Historically, these patients have been
treated with microsurgery through laparotomy and, in later
times, through laparoscopy. The result, measured as intrauterine pregnancy, is dependent on the status of the tubal mucosa.
As IVF has developed, the majority of patients have been
referred to IVF, but this subgr oup of patients with hydrosalpinx
was found to have a poor prognosis. The impaired outcome has
been demonstrated in several retrospective studies, summarized in meta-analyses showi ng a reduction by half in clinical
pregnancy and delivery rates and a doubled rate of spontaneous
abortion in women with hydrosalpinx [1]. It is not completely
understood how the hydrosalpinx exerts its negative effects. The
main theories have focused on the hydrosalpingeal fluid and
its action through (1) possible embryotoxic properties; (2)
mechanical leakage into the uterine cavity causing endometrial
alterations hostile to embryo implantation and development; or
(3) simply mechanical washout of embryos.
This chapter will focus on the reproductive problems associated with hydrosalpinx, including diagnosis, with particular
focus on ultrasonography, and interventions to enhance outcome after IVF.
Diagnosis of tubal disease
The diagnosis of tubal disease is mainly based on the failure to
detect tubal patency with laparoscopy, hysterosalpingography
(HSG), or hysterosalpingo-contrast sonography (HyCoSy).
Chlamydia antibody testing contributes to the evaluation of
risk for tubal disease, although without giving any information
on the structural appearance of the tubes.
Pelvic sonography is commonly performed in patients with
a clinical diagnosis of pelvic inflammatory disease. Although
the examination may be normal or sometimes nonspecific,
there are a variety of findings that are charac teristic of this
process. Understanding of the sonographic features of pelvic
inflammations, salpingitis, pyosalpi nx, tubo-ovarian complex,
and tubo-ovarian abscess will allow the interpreter to make
more specific, clinically useful diagnoses. Furthermore, sonography can help to distinguish acute from chronic abnormalities
in the fallopian tubes. This is of high importance in the assessment of the infertile couple.
In the followi ng sections we will discuss the usefulness of
ultrasound in diagnosing normal and abnormal fallopian tubes
using two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasonography (TVS) and hysterosalpingo-contrast
sonography (HyCoSy).
2D Transvaginal ultrasonography
On standard TVS, normal fallopian tubes are commonly not
visualized and dilated fallopian tubes have usually a nonspecifi c
appearance and often are indistinguishable from other pelvic
fluid collections and masses.
The most consistent sonographic feature of fallopian tube
dilatation is a tubular “sausage”-shaped structure with a fold
configuration. The wall of the structure is typically well defined
and echogenic. The echogenic appearance has been described in
patients with acute salpingitis [2,3]. Often linear echoes protruding into the lumen, a feature that may be related to the
wrinkled nature of the fallopian tube epithelium, are seen [2,3].
Distended pelvic veins, a common finding on TVS, have a
tubular appearance when imaged along their long axis.
However, blood flow within them usually causes multiple lowlevel moving echoes on real-time sonography. Bowel loops can
also resemble dilated fallopian tubes, but peristaltic motion is
almost always evident in bowel loops, even if only transiently.
The rectosigmoid colon is easily identified by administering a
water enema, and the colon often has distinctive haustral
markings.
Ultrasonography in Reproductive Medicine and Infertility, ed. Botros R. M. B. Rizk. Published by Cambridge University Press. © Cambridge
University Press 2010.