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18 Ultrasound in Follicle Monitoring for Ovulation Induction/IUI
239
of pregnancy. Commonly used ovulation induction medications include clomiphene citrate,
human menopausal gonadotropin, purifi ed FSH,
and recombinant gonadotropins. Although all of
these medications result in the development of
multiple follicles, they act via different
mechanisms.
Transvaginal sonography has a vital role in
monitoring the follicular growth rate in women
receiving ovulation induction medications.
In an elegant prospective study, Baerwold
et al. [ 4 ] compared the growth rate of ovarian fol-
licles during natural cycle and ovarian stimulation cycles using standardized techniques.
While the growth rate in natural cycles was
1.42 mm per day, the growth in stimulated cycles
was signifi cantly greater, i.e., 1.7 mm per day.
Continued research on the effect of greater follicular growth rates and shorter intervals to ovulation is being conducted (Fig. 18.7 ).
The baseline scan of the pelvis is mandatory
to rule out ovarian or uterine pathology and
assess the ovarian reserve: moreover one needs to
rule out the presence of ovarian cysts [ 3 ].
The objectives of a baseline scan are:
A . To rule out ovarian or uterine pathology
requiring attention prior to beginning infertility treatment (see Table 18.1 )
A common adnexal fi nding, endometrosis
[ 20 ], can be seen in over 30 % of women with
clinically defi ned infertility. Endometriosis is
defi ned as the extrauterine presence of endo-
ab
cd
Fig. 18.7 Serial transvaginal ultrasonographic images of
the right ovary of a research participant on days 1 ( a ), 4
( b ), 7 ( c ), 11 ( d ), 16 ( e ), and 17 ( f ) of a spontaneous men-
strual cycle. The same ovarian follicle is identifi ed
throughout the growth phase in (a–e). The corresponding
corpus luteum on the day of ovulation is shown in (e)
(Reprinted from Baerwald et al. [
from Elsevier)
4 ]. With permission
240
J. Blankstein et al.
ef
Fig. 18.7 (continued)
Table 18.1 Common adnexal masses
Cystic masses Follicular cyst, corpus/luteum cyst,
hydrosalpinx, dermoid cyst,
endometrioma/hemorrhagic cyst
Solid masses Fibroma, dysgerminoma, teratoma,
carcinoid subserosal fi broid
Complex masses Dermoid cyst, cyst adenoma,
granulosa
metrial tissue and is likely due to retrograde
menstruation and/or immunologic variations
or defi ciencies within the peritoneal cavity.
In mild cases small lesions are often located
on the ovarian and peritubular surfaces. Cases
of minimal endometriosis are not amenable to
ultrasonographic diagnosis. However, in more
moderate cases, one can visualize an endometrioma, i.e., a cystic structure which is lined
with endometrial epithelium which can involve
one or both ovaries, uterosacral ligaments, etc.
Endometrioma may appear as an ovarian
cyst with an echo-dense appearance of blood
within a cyst; the appearance may range from
anechoic to solid, depending on the amount
and organization of the blood within the cystic
structure; commonly one can visualize lowlevel echoes evenly distributed throughout the
cyst (Fig. 18.8 ).
It is important for the physicians to familiarize the ultrasonographic picture of the
endometrioma in order to avoid aspirating the
cyst because of an increased risk of infection,
compared with aspiration of a simple cyst.
Fig. 18.8 Endometrioma ultrasound study (note the
homogenous, low-level echoes, “ground glass” appearance)
Since ovarian teratomas are the most common ovarian neoplasm especially in reproductive-age women [ 21 ], one may encounter them
during a baseline scan; the ultrasonographic
fi ndings will depend on which elements are
present: ectoderm, mesoderm, etc. Very often
one can appreciate an echogenic mass with
acoustic shadowing. The presence of ectodermal elements gives irregular and variable
internal echogenicity (Fig. 18.9 ).
B . Check ovarian reserve : which will help iden-
tify the ideal treatment protocol
Markers of ovarian reserve are associated
with ovarian aging as they decline with chronologic age and hence may predict stages of
reproductive aging including the menopause
18 Ultrasound in Follicle Monitoring for Ovulation Induction/IUI
241
Fig. 18.9 Teratoma ultrasound study (note the echogenic
linear speckles). ( asterisk ) shows echogenic mass,
( arrows ) shows echogenic linear speckles
transition. Assessment of ovarian reserve
includes measurement of serum folliclestimulating hormone (FSH), anti- Mullerian
hormone (AMH), and inhibin B. Ultrasound
determination of antral follicle count (AFC),
ovarian vascularity, and ovarian volume also
can have a role. In infertile women, ovarian
reserve markers can be used to predict low
and high oocyte yield and treatment failure in
women undergoing in vitro fertilization [ 22 ].
Small antral follicles (<6.0 mm) measured
using 3D ultrasound and AMH show little
intra-cycle variation and perhaps should be
evaluated in prediction of ovarian reserve
independent of menstrual cycle [ 23 ].
In our clinic a baseline scan involves antral
follicle count and evaluation of ovarian volume. The number of antral follicles of at least
2 mm in diameter can be detected using ultrasound imaging; generally follicles that are
greater than 2 mm in diameter are highly
responsive to gonadotropins; however, some
follicles in this size range may be in the early
stages of atresia. Antral follicle count is performed on day 2–4 of a natural cycle or following pituitary downregulation. Prospective
studies assessing antral follicle count demonstrate that lower counts (less than four follicles) are associated with signifi cantly
decreased pregnancy rates and increased
cycle cancellation rates [ 24 ].
Low AFC did predict a higher cancellation
rate. Antral follicle count did not predict
implantation rate, pregnancy rate, or live birth
rate per cycle start. Antral follicle count may
be helpful in determining stimulation protocol, as it is the most reliable determinant of
oocytes retrieved per starting FSH dose.
Antral follicle count predicts ovarian response,
not embryo quality or pregnancy [ 13 ].
Ovarian volume is measured
using the following formula: volume
(cm 3 ) = length × width × anterior posterior
diameter × 0.53. In a prospective crosssectional study, it has been shown that ovarian volume, number of follicles, and total
follicular volume decreased signifi cantly
with age [ 25 ].
It has been shown that ovarian volume is
inversely correlated with age. Signifi cant
decrease in ovarian volume is observed in
women older than 35 years of age. The prognostic practicality of measuring early follicular ovarian volume is limited because
clinically meaningful changes are only manifest at the physiologic extremes [ 26 ].
However, one has to note that ovarian volumes less than 3 cc are associated with a signifi cant decrease in clinical pregnancy rates.
C . Ovarian cyst/hydrosalpinx
It is important to identify cysts and/or
hydrosalpinx prior to stimulation since
these situations could later be misinterpreted as developing follicle. Moreover,
basal ovarian cyst signifi cantly reduces ovulating events in patients treated with clomiphene citrate [ 27 ]. Thus, the recommendation
is to do a routine ultrasound screening in
those patients with a history of prior cysts,
as they are more likely to have a recurrent
cyst and those not ovulating on clomiphene
citrate.
Upon detection of an ovarian cyst, a conservative approach is generally effective. One
can wait for a spontaneous menstrual bleed
which indicates that endogenous ovarian hormone levels returned to base level; if the cyst
is not resolving and hormone levels of E 2 are
high, then cyst aspiration prior to stimulation
remains a viable option.
242
J. Blankstein et al.
Upon detection of suspect hydrosalpinx,
confi rmatory hysterosalpingogram and/or
laparoscopy is indicated. Signifi cant international data supports the observation that
hydrosalpinx lowers the success rate for IVF
and related ART procedures. It is thought that
the mechanism of action involves the retrograde fl ow of infl ammatory fl uid into the uterine cavity and resultant inhibition of embryo
implantation.
Selection of Patients
The ovulatory treatment options are based on
WHO classifi cation with patients separated into 3
main groups (see Table 18.2 ):
Group I : Hypothalamic-pituitary failure included
women with primary or secondary amenorrhea,
low levels of endogenous gonadotropins, and
lack of endogenous estrogen activity. The
treatment of choice for this group of patients
is gonadotropic therapy.
Group II : Hypothalamic-pituitary dysfunction
included patients with anovulation associated
with a variety of menstrual disorders whose
serum gonadotropin levels were within the
normal range and who had evidence of endogenous estrogen activity.
The treatment of choice for patients belonging
to Group II is a chlorotrianisene analogue,
such as clomiphene citrate.
Group III : Includes patients with high FSH levels
and the only viable option for them is ovum
donation.
Table 18.2 Anovulation treatment options (based on
WHO classifi cations)
Group I Option I Option II
Low FSH GnRH (pulsatile)
Gonadotropins
Bromocriptine Gonadotropins,
bromocriptine, and
clomiphene citrate
Group II Clomiphene
Normal FSH Surgical approach
Group III Ovum donation
High FSH
citrate
Gonadotropins
The above classifi cation is based on hormone
levels of FSH and estrogens; however, some conclusions can be drawn following a baseline ultrasound evaluation of the endometrium. In cases
where the endometrium is thick (7–14 mm), one
can conclude that the patient had suffi cient ovarian estrogen secretion and normal FSH level (i.e.,
Group II).
If on the other hand the endometrium is thin,
the patient has low estrogen level, and in this
case, a single FSH level will differentiate between
Group I (low FSH) and Group III (high FSH).
Technical Tips on How to Scan the Ovaries and Follicular Growth
Ovaries : The ovaries are located posterior to the
broad ligament and anteromedial to the internal
iliac vessels which are easily located and can be
used as a land mark for ovarian localization;
moving laterally from the endometrial canal will
produce the image of the ovary adjacent to the
iliac vessels.
The pelvic organs may be scanned either
transabdominally or transvaginally. In most
infertility units, transvaginal ultrasound has
become the routine method since it improves
spatial resolution; however, it has a smaller fi eld
of view. During the transvaginal approach, only a
few centimeters separate the probe from the
ovaries.
The best way to locate the ovaries is to scan
along the lateral margin of the uterus in transverse plane from the fundus to the cervix. In
cases where you cannot locate the ovaries, look
for them adjacent to the iliac vessels, which are
usually easily identifi ed, or try to follow the fallopian tube laterally.
In cases when the ovary is high in the pelvis, a
transabdominal scan is also necessary; in these
situations begin with the abdominal transducer
perpendicular at the midline just superior to the
symphysis pubis. Once you locate the long axis
of the uterus, move the transducer lateral until the
ovary is located. Again remember that the internal iliac vessels are located immediately posterior to the ovary.
18 Ultrasound in Follicle Monitoring for Ovulation Induction/IUI
243
Follicle : The spatial resolution of transvaginal
scans is 2–3 mm, so small follicles can be visualized easily as echo-free structures which usually
lie towards the periphery of the more echogenic
ovarian tissue. Since the follicles may be fl attened in one plane or have their shape altered due
to pressure, the internal diameter of the follicle
should be measured in three planes and the mean
value calculated. The intra-observer standard
deviation of transabdominal follicular measurement was reported in one study to be 0.6 mm, and
the inter-observer standard deviation is 1.2 mm,
irrespective of the follicular diameter. Thus, the
95 % confi dence limits for any particular measurement should be 2.4 mm [ 3 , 28 ], and one
would expect transvaginal measurements to confer even greater accuracy [ 16 ].
Follicles can be confused with blood vessels
(hypogastric vein), and they can be differentiated
by rotating the transducers. If the structure is a
vessel, it will appear tubular following rotation.
A baseline scan should always be done to
identify cystic structures which could later be
misinterpreted as follicles.
Sono AVC ( Automatic Volume Calculation ):
Recently a new software program (GE) with 3D
data set, which can automatically estimate the
diameter and volume of each follicle, has been
developed; this ultrasound program will automatically identify the ovarian follicle and the volume
for each follicle (Fig. 18.10 ).
Raine-Fenning et al. [ 29 ] compared automatic
volume measurement of each follicle to manual
measurements from 2D and 3D ultrasound; Sono
AVC provided measurements that were more
accurate than manual measurements, and obviously the time taken for measurements was signifi cantly shorter.
Fig. 18.10 Sono AVC ultrasound study: automatic estimation of diameter and volume. Each volume is separately
color coded (see text)
244
J. Blankstein et al.
Fig. 18.11 The impact of
ovulation induction treatment
on endometrial thickness
(Clomid black ; FSH white )
(Reprinted from Bromer et al.
42 ]. With permission from
[
Elsevier)
12
11
10
9
8
7
6
Endometrial thickness (mm)
5
4
12345678910
Clomiphene Citrate
Clomiphene citrate (CC) is a nonsteroidal triphenylethylene compound currently used as the fi rst
choice of treatment for induction of ovulation in
anovulatory or oligo-ovulatory women.
Mode of Action: The stereoscopic confi guration of CC is suffi ciently similar to that of
ß- estradiol to complete with it for available estrogen receptor sites in all estrogen-dependent target cells such as the hypothalamus, pituitary,
ovary, uterus, and cervical glands.
The mode of action of CC in the induction of
ovulation may be tentatively described as follows. “Blinded” by CC molecules occupying
the estrogen receptor sites, the hypothalamus
and pituitary are unable to correctly perceive
true serum estrogen levels. A false message of
insuffi cient estrogen concentration is registered
and acted upon, resulting in exaggerated FSH
and LH secretion. The occupation of hypothalamic estrogen receptors by CC is a short duration, time- limited process. A fair chance exists
that by the time ovarian follicles that are stimulated by the CC-induced gonadotropin elevation
reach the preovulatory stage, the hypothalamus
is already free of CC infl uence and ready to perceive the correct steroid signal. From this moment
Clomid
FSH
11 12 13 14 15 16 17 18 19 20
Cycle day
forward, the events are regulated and controlled
by the endogenous feedback mechanisms within
the hypothalamic-pituitary-ovarian (HPO) axis.
Considering its mode of action, an antiestrogen such as CC should be effective in patients
having a hypothalamus capable of releasing
pulsatile GnRH, a pituitary gland capable of
responding to GnRH, and an ovary containing
normal primordial follicles. Clomiphene citrate is
most effective when used in patients with hypothalamic-pituitary dysfunction. These patients
lack the proper regulation within the HPO axis,
but they have some endogenous GnRH secretion and estradiol production. These anovulatory
women probably have irregularities in the pulsatile secretion of GnRH, even though they do have
fl uctuating, detectable levels of gonadotropins
and estrogens.
Antiestrogenic Effects on the Cervix and Endometrium
The antiestrogenic effect of CC may exert an
adverse effect on the uterus and the cervix
(Fig. 18.11 ). This detrimental effect, caused by
the drug’s competition for estrogen receptors is
claimed to be one factor responsible for the
18 Ultrasound in Follicle Monitoring for Ovulation Induction/IUI
ab
Fig. 18.12 ( a ) Cervical canal measurement near ovulation and ( b ) after ovulation (Reprinted from Wolman et al. [ 31 ].
With permission from Elsevier)
245
discrepancy between the ovulation rate (85 %)
and the pregnancy rate (43 %) of women receiving CC treatment. Jirge and Patil [ 30 ] have dem-
onstrated in a prospective crossover study that the
number of follicles at the assumed time of ovulation is signifi cantly higher in patients treated with
clomiphene citrate; moreover, the endometrial
thickness on the same day was signifi cantly
smaller (7.6 mm vs. 8.5 mm). Most investigators
report decreased secretion of mucus from the cervical glands caused by antiestrogenic agents such
as CC. The antiestrogenic effect on the cervical
mucus, when present, is expressed by a decreased
amount of mucus, which occurs despite the relatively high levels of estrogen in the circulation.
Wollman et al. [ 31 ] demonstrated that the cervi-
cal mucus can be visualized in many patients
around the time of ovulation using pelvic ultrasound (see Fig. 18.5 ). In many patients given CC,
the cervical mucus does not exhibit any depressed
effects. To understand this phenomenon, we must
remember that the antiestrogenic effect on the
hypothalamus will result in elevated circulating
FSH and LH levels. The elevated gonadotropin
levels may cause multifollicular development,
which in turn enhances estrogen production. The
elevated estrogen levels, fi ve to ten times higher
than in normal cycles, sometimes mask the antiestrogenic effect of CC and tamoxifen citrate in
the cervix and uterus (Fig. 18.12 ).
Treatment Schema and Monitoring of Clomiphene Citrate Therapy
Clomiphene citrate is administered orally in
50-mg tablets. Therapy should be initiated with
50 mg of CC over a period of 5 days, usually
starting on the fi fth day after the fi rst appearance
of spontaneous or progestin-induced menstrual
bleeding. Clomiphene citrate dosage is typically
increased in subsequent months until ovulatory
cycles become evident. Clomiphene-citrateinduced ovarian cysts often resolve spontaneously and typically do not require intervention.
In addition to the baseline scan, we advocate
cycle monitoring via ultrasonographic evaluation
of follicular size, endometrial thickness, and cervical mucus observation. Ultrasound monitoring
of patients undergoing ovulation induction cycles
will ensure adequate follicular recruitment and
identify those patients not responding or have
delayed endometrial thickening. In cases where
there is concern that cervical mucus is insuffi cient, often due to the antiestrogenic effect of
Clomid, intrauterine insemination (bypassing the
cervix) is probably the best solution. Whenever
the endogenous feedback mechanism responsible for the preovulatory LH surge is not properly
activated, the midcycle LH peak may consequently be inadequate, ill-timed, or entirely
absent. In such instances hCG should be
246
J. Blankstein et al.
administered to induce ovulation. Optimal timing
for hCG ovulation trigger injections includes
ultrasonographic measurement of mean follicular
diameter ranging 19–20 mm. Ovulation will
occur 34–36 h following hCG injection, so the
IUI is often performed 34 h later. Recently Paltnik
et al. [ 5 ] have shown that higher pregnancy rates
were achieved when the leading follicle was in
the 23–28 mm range.
Universal agreement is lacking as to when to
introduce ultrasonographic cycle monitoring versus less complicated or costly alternatives.
However, we agree with the predominant opinion
that the additional ultrasound expense is justifi ed
by the prevention of protracted periods of ineffective therapy [ 32 ]; moreover it has been shown
that a signifi cant number of women (14 %) developed 3 or more follicles, despite receiving low
doses of clomiphene citrate [ 33 ].
Gonadotropins
Principles of Gonadotrophic Therapy: In order to
optimally stimulate follicular maturation, both
FSH and LH are required. While FSH content of
the pharmacologic preparation is essential for
follicular development, fi nal maturation of the
follicles and subsequent ovulation are brought
about by a pituitary release and circulatory surge
of LH. Thus two gonadotropins are required for
induction of ovulation: one providing the required
amount of FSH and another providing LH or
LH-like material (hCG) of suffi cient quantity to
provoke ovulation and corpus luteum formation.
Well accepted ovulation induction protocols
include alterations in the precise ratio of FSH
to LH.
Selection of Patients: Ideal candidates for
ovulation induction with gonadotropins are
patients who have low endogenous gonadotropin
secretion and are amenorrheic or anovulatory
(Group I—WHO). This treatment can also be
given to patients with hypothalamic-pituitary
dysfunction (Group II), including anovulatory
patients associated with a variety of menstrual
disorders. The treatment of choice for patients
belonging to Group II is a clomiphene citrate
alone or in conjunction with estrogen and/or
hCG. Patients who fail to ovulate or conceive
within a reasonable time are considered “clomiphene failures” and can be considered for hMG
therapy.
Monitoring of Therapy: Gonadotropins are
given daily by injection in order to stimulate follicular development; ovulation is actually induced
by hCG. The daily dose of gonadotropins given
in a particular cycle depends upon the ovarian
response of the patient in that particular cycle.
The response is refl ected by a growth of follicles
accompanied by biochemical changes mainly
with respect to increased synthesis and secretion
of steroidal hormones. The follicular enlargement can be visualized by ultrasonographic measurement, while estrogen secretion values can be
estimated directly by blood measurement.
Ultrasonographic monitoring of treatment
cycles serves to assess the effective dose required
to evoke an ovarian response, the length of time
required for follicular maturation, and the appropriate time for induction of ovulation.
Furthermore, such monitoring should aim to prevent ovarian hyperstimulation syndrome (OHSS),
or at least lead to early detection. For these purposes, a combination of ultrasonography and
estrogen determination was advocated. Given
that exogenous gonadotropic stimulation usually
induces the development and growth of several
follicles, ultrasonographic monitoring is particularly advisable for these treatment cycles.
Sonographic visualization may thus discriminate between single and multiple follicular
growths, and their measurement may aid in the
interpretation of the meaning of the estrogen
levels. Evidence is accumulating that follicles
of diameters greater than 18–19 mm should be
“ovulated.” Thus, sonography can be a more precise indicator for the determination of the optimal ovulatory timing. Gonadotropin treatment
is often started on the fi fth day of spontaneous
or induced bleeding. It is safe to start with low
doses of gonadotropins with close ultrasonic
18 Ultrasound in Follicle Monitoring for Ovulation Induction/IUI
Fig. 18.13 Multiple
follicles – ultrasound study
247
monitoring to ensure appropriate follicular
growth and development (Fig. 18.13 ).
Follicular development should be monitored
with frequent ultrasound studies. Ultrasound
plays a critical role in assessing response to
gonadotropins and timing of hCG administration.
A baseline ultrasound scan is suggested in the
early follicular phase to determine the presence
or absence of persistent follicles. Scanning
should become more frequent when the follicle
reaches 14 mm or greater. When a follicle 18 mm
or greater is identifi ed, hMG is discontinued, and
hCG is administered 24 h later to cause ovum
release. Usually 10,000 units of hCG, injection,
are given to trigger ovulation.
While in the past it was emphasized that
ultrasound scanning should be complimentary to
estradiol data, Shoham et al. [ 34 , 35 ] have raised
the question of whether it is possible to run a successful ovulation induction program based solely
on ultrasound monitoring. In their prospective
study, monitoring of ovulation induction was
performed using serial ultrasound measurements
and correlated with the patient’s E 2 concentrations that became available at the end of each
cycle. Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients
received treatment with gonadotropins. The
results of this study demonstrated that transvaginal ultrasound fi ndings including (a) follicular
growth, (b) uterine measurements, and (c)
endometrial thickness all strongly correlated
with serum E 2 concentrations ( P < 0.0001).
Shoam et al. concluded that serial ultrasound
examinations used alone (eliminating determination of serum E 2 levels) have proven to be an
effective monitoring approach for ovulation
induction cycles.
Wiser et al. [ 36 ] studied two groups of patients
undergoing their fi rst IVF treatment. The
ultrasound- only group (study group) was monitored by US for follicle size and endometrial
thickness without blood tests. In this group, only
one blood test was taken before human chorionic
gonadotropin (hCG) injection to ensure a safe
level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control
group was monitored by ultrasound plus serum
estradiol and progesterone concentration at each
visit. No differences were found between the
groups. The conclusion of the study was that
ultrasound as a single monitoring tool for IVF
cycles is reliable, safe, and patient friendly and
reduces treatment expenses.
248
J. Blankstein et al.
Clomiphene Citrate and hMG
The rationale of clomiphene citrate followed by
hMG is the utilization of the former to increase
FSH in the initial phase (recruitment and selection) and maintain adequate FSH levels by administration of hMG during follicular growth phase.
It has been shown that by using the combined
clomiphene citrate/hMG protocol in normogonadotropic patients, they could reduce the necessary hMG requirement by 50 %. Abdelazim and
Makhlouf [ 37 ] compared sequential clomiphene
citrate/hMG regimen to hMG regimen for ovulation induction in clomiphene citrate-resistant
women. They found that the sequential CC/hMG
regimen is as effective as hMG regimen for ovulation induction, produces satisfactory pregnancy results, and reduces treatment cost.
The clomiphene citrate/hMG treatment scheme
is as follows: on the fi fth through the ninth days
after induced or spontaneous bleeding, the normogonadotropic patient receives 100 mg of clomiphene citrate daily. From the eighth day
onwards, hMG is administered. The patient is
carefully monitored by estrogen determination
and ultrasound visualization of the growing
follicle(s). This will help to determine if and when
the ovulatory dose of hCG should be administered
and to prevent hyperstimulation and multiple
pregnancies.
The Help of Ultrasound: Assessing Complications
Multiple Pregnancies: The major adverse effects
of induction of ovulation are multiple pregnancies and OHSS.
Five to eight percent of clomiphene-induced
pregnancies and 15–25 % of all pregnancies following gonadotropin-induced ovulation are multiple gestations.
While almost all of the multiple gestations
conceived on clomiphene will be twins, 30 % of
multiple gestations following gonadotropin therapy will be triplets.
Poorly monitored ovulation induction is probably the major cause of the multiple pregnancy
Table 18.3 Complications associated with twin pregnancy
Maternal complications Fetal complications
Anemia Premature delivery
Preeclampsia/eclampsia Diffi cult delivery
Pre-/postpartum hemorrhage Prolapse of an umbilical
cord
Hypoxia of second twin
epidemics. Table 18.3 summarizes the clinical
complication associated with twin pregnancies. It
is important to diagnose multiple pregnancies
early, in the fi rst trimester, so women who conceive with high-order multiple pregnancies may
consider multiple pregnancy reduction.
In cases of twin pregnancy, it is recommended
by the AIUM to document amnionicity and chorionicity in the early fi rst trimester, so one can
prepare for high-risk situations such as a monochorionic twin gestation.
In many countries, triggering of ovulation
with hCG is only done if there are no more than
two mature follicles around the assumed time of
ovulation.
Adhering to strict guidelines involving ultrasound monitoring will defi nitely reduce the incidence of multiples.
Ovarian hyperstimulation is the most serious
complication which in extreme situations is
potentially life threatening and the reader is
referred to Chap. 23 .
It is important to understand the risk factors
that can be identifi ed in high-risk patients before
ovulation is being induced. The presence of polycystic ovaries put the patient at increased risk; we
have shown that a decrease in the fraction of the
mature follicles and an increase in the fraction of
the very small follicles around the assumed time
of ovulation correlated with an augmented risk
for the development of severe stimulation of the
ovaries. Our data suggest [ 38 ] that ultrasonogra-
phy is of good predictive value in the occurrence
of clinically moderate to severe OHS in women
treated by hMG and hCG. Even with estrogen
levels within accepted normal limits, it is suggested that hMG/hCG administration should be
interrupted in the presence of 11 or more preovulatory follicles, especially if most of them are
immature (<9 mm).