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Figure 7.2.1. Hysterosalpingogram demonstrating a filling defect
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(arrow). Subsequent hysteroscopy revealed a 1 × 2 cm endometrial
polyp.
Transvaginal Sonography
Transvaginal sonography (TVS) is safe, relatively noninvasive,
and readily available in most clinics. Because of these features,
sonography has been advocated as an initial screening modality
in patients with infertility. In addition to screening for uterine
pathology, the position of the uterus and angle of the uterocervical canal can be recorded for optimization of future intrauterine catheterization. The phase of the menstrual cycle affects the
appearance of the endometrial echo. In the late proliferative
phase, a trilaminar appearance is appreciated (Figure 7.2.2). Following ovulation, the endometrial echo in the secretory phase is
more homogeneous and opaque.
With the use of a high-resolution transducer, TVS is capable
of detecting endometrial polyps (Figure 7.2.3), leiomyomata and
Figure 7.2.2. Transvaginal ultrasound of the uterus demonstrating a
normal trilaminar image of the endometrium (arrow).
Assessment of the Endometrial Cavity in the Patient with Infertility — 97
Figure 7.2.3. Transvaginal ultrasound demonstrating an endometrial
polyp (arrow). The patient also had an HSG performed, which is
depicted in Figure 7.2.1.
at times intrauterine synechiae (see Figure 7.2.6), and mullerian
abnormalities such as bicornuate or septate uteri.[19]
TVS is limited by an inability to precisely localize intrauterine lesions and by the difficulty in delineating intramural from
submucosal leiomyomata. Additionally, the phase of the menstrual cycle may pose a challenge in the diagnosis of more subtle
intrauterine lesions. These limitations served as the impetus for
the development of sonohysterography, a technique that combines sonography with distention of the endometrial cavity.
Sonohysterography
Sonohysterography, or saline infusionsonography (SIS), involves
the instillation ofsaline into the uterinecavity during ultrasound.
This technique combines the advantages of TVS with a high level
of diagnostic accuracy, and is easily performed in the office setting.
As with HSG, sonohysterography is ideally performed in the
follicular phase after the cessation of menses. An insemination
catheter without an anchoring balloon can be successfully usedin
the nulliparous patient. However, for the patient with a patulous
cervix, a balloon catheter system is recommended. A prospective
study of six different catheter systems found no significant differences among them in terms of reliability and ease of use.[20]
Using sterile technique, intracervical placement of a primed balloon catheter is performed. Warmed saline or Ringer’s lactated
solution is slowly infused and the cavity scanned in both longitudinal and transverse planes. If a balloon catheter is used, the
balloon should be deflated at the conclusion of the procedure to
allow for assessmentof the lower uterine segment.Complications
are rare. Crampingand/or vasovagal symptomsoccur in lessthan
9% of patients.[21]Therisk of infectionisreported to be lessthan
1%.[22]
Sonohysterography appears to be superior to HSG in the
detection of intrauterine pathology, correctly identifying 90% of
abnormalities among infertile patients.[23] These dataare consistent with thoseobserved in patientswith abnormal uterinebleeding in the general gynecologic setting, where sonohysterography
has sensitivities of 87% and 93% in the detection of intrauterine pathology and endometrial polyps, respectively.[24,25]
98 — Richard O. Burney and Amin A. Milki
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Table 7.2.1: Comparison of Techniques to Evaluate the Endometrial Cavity in an Infertile Population (as Compared with
Hysteroscopy)
Diagnostic Method Patients, no. Sensitivity,% Specificity,% Study
HSG 106 79 60 Raziel et al. (1994) [26]
HSG 464 98 15 Golan et al. (1996) [27]
HSG 216 80 70 Wang et al. (1996) [28]
HSG 62 73 100 Alatas et al. (1997) [23]
TVS 62 36 100 Alatas et al. (1997) [23]
TVS 38 81 95 Ayida et al. (1997) [29]
TVS 98 91 83 Ragni et al. (2005) [30]
Sonohysterography 62 91 100 Alatas et al. (1997) [23]
Sonohysterography 38 88 100 Ayida et al. (1997) [29]
Sonohysterography 98 98 94 Ragni et al. (2005) [30]
Compared with conventional transvaginal ultrasound, sonohysterography has both higher sensitivity (93% vs. 65%) and specificity (94% vs. 76%) for the detection of endometrial polyps in
the patient with abnormal bleeding.[25]
Hysteroscopy
Hysteroscopy is regarded as thegoldstandard against which other
imaging modalities are compared (Table 7.2.1).
Office hysteroscopy has become increasingly popular in the
assessment of the endometrial cavity. The ability to perform this
procedureintheofficesettingisaconsequenceofseveraladvancements. First, the development of small, 3.1- to 3.5-mm flexible
and 3- to 5-mm rigid hysteroscopes has obviated extensive cervical dilation beyond 5 mm. Second, advancement in anesthetic
medication has facilitated patient tolerance of the procedure.
Finally, the development of a coaxial bipolar electrode system
for use with crystalloid distention media has improved both the
tolerance and safety of the procedure.
The preoperative assessment of the patient undergoing hysteroscopy should include a transvaginal ultrasound in the office.
This affords high-resolution screening of the uterus for large
uterine abnormalities. Patients with submucosal fibroids greater
than 1.5 cm or major uterine malformations should be triaged
to operative management in an operating room rather than an
office setting. Additionally,transvaginal ultrasound allows assessment of uterine position. An anteverted uterine position is found
in approximately 74% to 90% of nulliparous women, demonstrated in studies using either ultrasound [31] or magnetic resonance imaging [32] of uterine position. Advising the patient
with an anteverted uterus to present with a full bladder at the
time of hysteroscopy serves to straighten the cervicouterine canal
and facilitates cervical dilation and subsequent placement of the
hysteroscope. Contraindications are similar to those for HSG.
Patients suspected of having an active pelvic infection should not
undergo hysteroscopic evaluation until the infection has completely resolved.
To optimize visualization of the endometrial cavity during
hysteroscopy, the procedure should be performed during the
early to mid-follicular phase of the cycle. This also minimizes
the possibility of pregnancy. Pharmacologic treatments to minimize endometrial interference with the procedure include oral
contraceptives and GnRH agonists. These pretreatments serve
to further minimize endometrial thickness at the time of anticipated hysteroscopy.Thehysteroscopy is thenoptimallytimed 4 to
5 weeks after administration of the GnRHagonist. In patients for
whom a nonelectrolyte distending medium is planned, a GnRH
agonist for endometrial preparation may also reduce the cerebral
risks associated with dilutional hyponatremia.[33] For patients
undergoing IVF, the procedure can be conveniently scheduled
during the oral contraceptive phase before controlled ovarian
hyperstimulation (COH). Such timing has been associated with
a significantly improved pregnancy rate when compared with a
longer interval between office hysteroscopyandIVFcyclestart.[3]
Patient tolerance of office hysteroscopy has been optimized
by advancements in pain control medication regimens. Excellent
acceptance of diagnostic hysteroscopy using a 5-mm scope without analgesia has been reported.[34] However, when the possibility of an operative component to the office hysteroscopy
exists, pain medications should be considered. A regimen that
includes a benzodiazepine such as diazepam, a narcotic such
as acetaminophen with hydrocodone, and a nonsteroidal antiinflammatory medication such as intramuscular ketorolac provides excellent pain control when coupled with a paracervical
block. Alternatively, conscious sedation with intravenous fentanyl and midazolam can be coupled with the paracervical block.
Typically, patients receiving conscious sedation require no more
than 1 mgof midazolam and 100μg of fentanyl for excellent analgesia. The paracervical block consists of a local anesthetic such
as 1% lidocaine without epinephrine in the amount of 5 to 7 mL
each injected at the 4 and 8 o’clock positions of the cervix.
Hysteroscopes for office use are currently manufactured in
both rigid and flexible forms. Those suitable for office hysteroscopy are typically 5 mm or less in outer diameter, thereby
requiring minimalcervical dilation. Importantly,these scopesstill
allow an operative channel. Theviewing angle may rangefrom 0
to 70◦from the horizontal. Though rigid hysteroscopes are more
commonly used, the flexible hysteroscopes provide an advantage in accessing the cavity of patients with difficult cervicouterine junctions and in visualizing the tubal ostia of patients with
◦
Table 7.2.2: Comparison of Distending Media
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Assessment of the Endometrial Cavity in the Patient with Infertility — 99
Factor Hyskon Sorbitol Saline CO
Availability Worst Intermediate Best Intermediate
Maintenance of distention Best Intermediate Worst Intermediate
Cleanliness Worst Intermediate Intermediate Best
Office use Worst Intermediate Best Best
Miscibility with blood Best Best Intermediate Worst
Ability to aspirate Best Intermediate Intermediate Worst
Flushing capability Intermediate Intermediate Best Worst
Operative capability Best Best Intermediate Worst
Complications Intermediate Intermediate Low Low
Maximum deficit 1500 mL
∗
Maximum fluid deficits per Committee on Hysteroscopic Fluid Guidelines of the American Association of
Gynecologic Laparoscopists.[39]
Modified from Baggish MS, Barbot J, Valle R, eds. Diagnostic and Operative Hysteroscopy: A Text and Atlas.New
York: Mosby-Year Book; 1989.
funneling of the cornua. Yet these situations are atypical, and the
choice of hysteroscope remains one of personal preference and
convenience.
The choice of distending media for use during office hysteroscopyincludesbothgasand liquid types (Table 7.2.2).Carbon
dioxide gas is the onlygas currently usedas a distending medium.
This medium must be introduced with an insufflator specifically
designed for hysteroscopic insufflation, with a maximal flow of
100 mL/minute and a maximum pressure of 100 mm Hg.[35]
In the past, the substitution of laparoscopic insufflators for hysteroscopic use resultedin casesof gas embolism. Fluid distending
media consist of both low-viscosity and high-viscosity subtypes.
Hyskon (32% dextran 70 and 10% dextrose in water; Pharmacia) represents a high-viscosity agent. Immiscible with blood,
Hyskonprovidestheadvantageofclear visualization during operative hysteroscopy involving resection of vascular endometrial
pathology. However, the thick consistency of this medium renders it somewhatdifficult to clean. Low-viscosityagents consist of
nonelectrolyte solutions, such as glycine, sorbitol, and mannitol,
and electrolyte solutions. The nonelectrolytes are ideally suited
to operative hysteroscopic techniques in which monopolar electric current is planned. With the exception of mannitol, these
media are hypo-osmolar, and therefore require careful surveillance of fluid status to minimize complications of hyponatremia
and decreased serum osmolality, such as cerebral edema. On the
other hand, mannitol 5% is iso-osmolar and has the advantage
of diuretic activity. Though fluid overload and attendant risk of
pulmonary edema are possible with electrolyte media, the risk
of hyponatremia is much less than that associated with nonelectrolytes. For diagnostic purposes, electrolyte media represent a
popular choice. Typically, less than 1 L of crystalloid such as normal saline or lactated Ringer’s is sufficient for the procedure. The
development of the coaxial bipolar electrode surgical system has
made current-based operative hysteroscopy possible using electrolyte as the distending medium. Several studies have demonstrated excellent patient tolerance of the bipolar electrosurgical
approach.[36–38]
2
∗
2500 mL
∗
The technique of office hysteroscopy is prefaced by adequate
patient counseling, which serves to minimize patient anxiety and
optimize tolerance of the procedure. After a sterile prep of the
vaginal vault, the cervix is gently dilated to sufficient diameter to
admit the hysteroscope. The scope can be advanced under direct
visualization. For difficult cervicouterine junctions, abdominal
ultrasound guidance may be used to help advance the hysteroscope safely. An easy passage of cervical dilators and hysteroscope
is critical, as this is the stage of the procedure at which most
uterine perforations occur. The rate of uterine perforation with
the procedure is 0.1% to 1.4%.[40] However, with a full bladder
in the patient with an anteverted uterus, ultrasound guidance,
and hysteroscopic visualization of the cervical canal, this complication can be significantly minimized if not eliminated. Once
the hysteroscope is advanced into the uterine cavity, patient discomfort can be reduced by adjusting the rate of distention media
inflow to a level that provides adequate visualization of the cavity.
A thorough evaluation of the cavity is performed. With oblique
scopes, the posterior segment of the cavity is readily visualized.
The scope mustbe angled toafford visualization ofthe lateral and
anterior aspects. Finally, the cornual regions and tubal ostia are
inspected. The availability ofvideo monitoring systems enhances
the patient experience by providing real-time feedback. This in
turn facilitates the postprocedural counseling of the patient.
The most important benefit of hysteroscopy is the ability
to immediately treat most pathology that is encountered (Table
7.2.3). Many hysteroscopesused in the office setting have an operative channel through which various instruments can be introduced. The targeted removal of endometrial polyps is afforded
by grasping forceps. Scissors can be used for the resection of
intrauterine synechiae and septi. The removal of submucosal
fibroids is conducted with the coaxial bipolar electrode. A variety
of tips allows the operator to tailor the instrument for the particular task. Significantly, all of these operative procedures can
be performed using electrolyte distention media. Studies have
demonstrated excellent surgical results with office hysteroscopic
procedures, with success rates of 98% to 100%.[41–43]
100 — Richard O. Burney and Amin A. Milki
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Table 7.2.3: Findings of 1000 Office Hysteroscopies before
In Vitro Fertilization
Findings Cases, no. (%)
Normal findings 618 (62)
Endometrial polyps 323 (32)
Submucous fibroids 27 (3)
Intrauterine adhesions 25 (3)
Polypoid endometrium 9 (0.9)
Septum 5 (0.5)
Bicornuate uterus 3 (0.3)
Retained products of conception 3 (0.3)
Taken with permission from Hinckley and Milki.[43]
Complications associated with office hysteroscopy are rare,
with a reported rate of 0.28% to 2.7%.[44,45] The rate of complication has been associated with the type of hysteroscopic procedure performed. Infection, bleeding,sequelaeof fluid overload,
cervical laceration, and uterine perforation are possible. A very
large retrospective survey of operative hysteroscopies performed
at multiple centers demonstrated an infection rate of 0.01%.[46]
However, theinvestigators acknowledgeuncertainty as towhether
antibiotic prophylaxis was used in a number of these procedures.
For patients deemed to be atriskfor endomyometritis, perioperative prophylaxis with an outpatient antibioticsuch as doxycycline
is advisable.
Bleeding sufficient to require intervention has been reported
to occur ata rate of0.5% to 1.9% ofoperative hysteroscopiccases.
This is less common in office hysteroscopic cases. Tamponade
with the intrauterine placement of a Foley catheter 30-mL balloon or with dilute vasopressin-treated uterine packing has been
described.[47,48] It is imperative to determine with certainty
whether the bleeding is consequent to uterine perforation. Lateral uterine or cervical perforations may result in significant
hemorrhage. Finally, fluid overload is a complication that is best
avoided by limiting excess fluid absorption. Guidelines for monitoring have been previously published.[39] Though patient size
and health status are important variables to consider in establishing a fluid deficit threshold, the procedure should be discontinued if the fluid deficit reaches 1500 mL of a nonelectrolyte
solution or 2500 mL of an electrolyte medium. In the office setting, electrolyte solutions are the medium of choice. Though
not associated with hyponatremic sequelae, excessive absorption of electrolyte solutions during hysteroscopy has led to pulmonary edema. Consequently, prophylactic fluid monitoring is
essential.
PATHOLOGY AFFECTING THE
ENDOMETRIAL CAVITY
Uterine pathologies that have been demonstrated to adversely
affect embryo implantation include endometrial polyps, leiomyomata, uterine septation, intrauterine synechiae, and DES. There-
Figure 7.2.4. Hysteroscopy demonstrating an endometrial polyp.
fore, the pathogenesis and management of each of these conditions deserves review.
Endometrial Polyps
Endometrial polyps represent the most common intracavitary
finding in the infertile patient population (Figure 7.2.4). Even in
the absence of abnormal uterine bleeding, endometrial polyps
may be discovered in women with infertility. The incidence of
asymptomatic endometrial polyps in women with infertility has
been reported to range from 10% to 32%.[43,49]
The influence of circulating estrogen on the development of
endometrial polyps is well documented.Inthe context of patients
undergoing hysteroscopy before in vitro fertilization, the high
incidence of endometrial polyps may be secondary to the hyperestrogenemia associated with prior gonadotropin cycles. Additionally,polyps tendto be increasingly common with patient age.
Polyps may be asymptomatic or associated with abnormal uterine bleeding. Grossly, endometrial polyps are pink–gray to white
with smooth, glistening surfaces. The tip or the entire polyp may
be hemorrhagic. Found most commonly in the uterine fundus
and cornual regions, polyps range from lesions millimeters in
size to those that occupy the entire endometrial cavity. A number
of other entities, including endometrial hyperplasia and carcinoma and sarcoma, may have a polypoid appearance. Hence, it
is important to obtain pathologic review of polyps, particularly
large or unusual appearing forms.
A comparison of imaging modalities in the detection of
endometrial polyps in the infertile population is presented in
Table 7.2.4.
Though the incidence of endometrial polyps in the infertile population is well defined, the etiologic significance of this
finding is more recently elucidated. In a retrospective study of
patients diagnosed with a polyp during COH, a trend toward
higher spontaneous abortion rates was observed.[50] A prospective study of 224 infertile women who underwent hysteroscopy
suggested a 50% pregnancy rate achieved with polypectomy.[51]
Finally, a randomized prospective study of 215 infertile patients
with sonographic diagnosis of endometrial polypswas conducted
to evaluate the impact of polypectomy on fertility.[18] Subjects
Assessment of the Endometrial Cavity in the Patient with Infertility — 101
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Table 7.2.4: Comparison of Techniques to Detect Endometrial Polyps in an Infertile Population (as Compared with Hysteroscopy)
Diagnostic Method Patients, no. Sensitivity,% Specificity,% Study
HSG 65 50 83 Soares et al. (2000) [17]
TVS 74 71 100 Shalev et al. (2000) [49]
TVS 65 75 97 Soares et al. (2000) [17]
TVS 98 81 92 Ragni et al. (2005) [30]
Sonohysterography 65 100 100 Soares et al. (2000) [17]
Sonohysterography 98 100 98 Ragni et al. (2005) [30]
were randomized to either hysteroscopic polypectomy or diagnostic hysteroscopy with polyp biopsy. The mean polyp size in
both groups was 16 mm. Patients in the polypectomy arm evidenced a relative risk of 2.1 (95% CI, 1.5–2.9) of achieving pregnancy as compared with patients in the polyp biopsy arm, with
65% of pregnancies in the polypectomy group achieved spontaneously. Interestingly, the authors did not find a significant relationship between polyp size and pregnancy outcome, suggesting
a possible biochemical interference with implantation posed by
the presence of an endometrial polyp. In sum, the evidence to
date supports the targeted removal of endometrial polyps in the
optimization of fertility outcomes.
Leiomyomata
Leiomyomata are the most commontumors ofthe uterus,occurring most commonly in women of reproductive age, particularly
in the 30s and 40s. The impact of fibroids on fertility depends on
the parameters of location, number, and size. Types of leiomyomata include subserosal, intramural, and submucosal varieties.
Submucous myomas, by virtue of their mass effect and inhospitable surface area for nidation, have been clearly associated
with infertility and with pregnancy loss. These myomas appear
as rounded masses that bulge tovarying extents into theendometrial cavity,and the overlying endometrium may be atrophic, congested, ulcerated, or hemorrhagic. Because of their intracavitary
location, submucosal fibroids may be effectively removed via a
hysteroscopic approach (Figure 7.2.5).
A comparisonof imaging modalities forthe detection of submucosal leiomyomata is provided in Table 7.2.5. Sonohysterography and hysteroscopy are equivalent in the detection of submucosal myomas. Whereas SIS offers the advantage of allowing
measurement of the overall dimensions of the lesion, office hysteroscopy may afford the removal of small submucous lesions in
the same setting.
The impact of intramural (defined as greater than 50% volume within the myometrium) myomas upon fertility remains
controversial. Although some studies showed reduced implantation and conception rates in women with intramural fibroids
[53,54], others have not demonstrated an adverse effect.[55,56]
One study demonstrated a size-dependent impact of intramural
myomas, with those measuring greater than4 cmassociated with
lower pregnancy rates following IVF/ICSI treatment.[57] The
mechanism by which intramural lesions may impair fertility is
unproven. Alterations inuterine artery blood flow, local cytokine
release, and/or gene expression profiles have been purported.
Insofar as leiomyomata cluster with other estrogen-dependent
disorders, such as endometriosis, adenomyosis, and endometrial polyps, their role in infertility may be purely associative.
Nonetheless, an in-depth review of six previously published trials concludedthat only intramural fibroids that resulted in cavity
distortion or impingement were deleterious to fertility.[58] The
beneficial effect of removing such cavity-distorting lesions was
validated in a recent case-controlled study.[59]
Finally, studies have consistently failed to find an impact of
subserosal leiomyomata (defined as ≥50% volume projecting
beyond the outer uterine contour) upon fertility.
Uterine Septation
With an incidence of 2% to 3%, uterine septation represents
the most common mullerian fusion defect.[60] Clinical sequelae of the septated uterus may include infertility, spontaneous
pregnancy loss in the first or second trimester, or late-trimester
pregnancy complications. However, pregnancy outcome in the
presence of a uterine anomaly may depend on the location of
blastocyst implantation ina particular cycle,and this mayexplain
the situation in which a woman with a septate uterus might
Figure 7.2.5. Hysteroscopy demonstrating a submucosal leiomyoma.
102 — Richard O. Burney and Amin A. Milki
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Table 7.2.5: Comparison of Techniques to Detect Submucosal Myomas (as Compared with
Findings at Hysterectomy)
Diagnostic Method Patients, no. Sensitivity,% Specificity,% Study
TVS 52 90 98 Cicinelli et al. (1995) [52]
Sonohysterography 52 100 100 Cicinelli et al. (1995) [52]
Hysteroscopy 52 100 100 Cicinelli et al. (1995) [52]
encounter recurrent pregnancy loss even after having delivered a
term infant.
Hysteroscopic septoplasty hasbeen demonstrated todecrease
significantly the risk for spontaneous abortion in women with
septate uteri, and surgical therapy is indicated in patients with
known uterine septi and a history of recurrent spontaneous
abortion.[61] Indications for surgical correction of septation
when the presenting complaint is infertility are less obvious.
Among seven series of hysteroscopicmetroplasties performed for
infertility,theoverall pregnancy rate aftertreatmentwas48%.[61]
It is still reasonable to consider surgical management in some
infertile patientswith uterine septibecause septoplasty maymaximize the chance of having a live birth by decreasing the associated
risks for spontaneous abortion and preterm labor.
The hysteroscopic approach to septum resection is often performed with microscissors, the resectoscope, or laser. The coaxial bipolar electrode surgical system, providing the advantage of
operating in a crystalloid distention medium, has been successfully applied toward hysteroscopic septum resection.[62]
Intrauterine Synechiae
About 13.5% of 74 infertile women scheduled for IVF treatment
were found to have intrauterine adhesions when evaluated with
diagnostic hysteroscopy.[49] Causes of intrauterine adhesionsare
often iatrogenic, with patient histories typically involving intraoperative or postoperative complications of uterine evacuations
for menorrhagia, pregnancy termination, or postpartum hemorrhage. Other causes ofintrauterinesynechiaeinclude intrauterine
infection with pathogens such as Schistosoma and mycobacteria.
In some third-world countries, tuberculous endometritis may be
an important cause of uterine factor infertility.[63] Tuberculous
endometritis differs from most other types of endometrial infection, and uterine scarring and infertility are significant sequelae
even after treatment.[64] Severe forms of Asherman’s syndrome
have been associated with amenorrhea, menstrual irregularity,
spontaneous abortion, and recurrent pregnancy loss.
Ultrasound can detect the presence of synechiae (Figure 7.2.6). The performance of TVS at midcycle (trilaminar
endometrium) rather than after menstrual cessation provides
better imaging of small intrauterine adhesions.[40]
Hysteroscopic resection is the method of choice for the management of intrauterine synechiae (Figure 7.2.7).
Postoperative prevention of reformation of adhesive disease
may involveestrogen therapy alone or incombinationwith intraoperative placement of an intrauterine device, such as a pediatric Foley catheter, for 7 days. It is thought that estrogen rapidly
rebuilds the endometrial lining after surgery and thereby prevents the development of scar tissue. A typical regimen consists
of conjugated estrogen at a dosage of 2.5 to 5 mg/day for 1 to
2 months. The surgical management of intrauterine adhesions
is reported to be very effective, with pregnancy rates above 80%
among patients treated for mild to moderate disease.[65]
DES Exposure
Exposure to DES in utero increases a woman’s risk for congenital reproductive tract malformations and obstetric complications, including preterm labor and cervical incompetence.[66]
In one study, almost 70% of women exposed to DES in utero
were noted to have uterine malformations on HSG. The most
common finding was the T-shaped uterus.[67] Whether DESexposed women also have higher rates of infertility remains
unclear.[68] One investigator reported that decreased fertility in
these women was particularly prevalent when constriction of the
upper segment of the uterus was present.[69] This question is
difficult to study, however, because there is great variation in
the degree of congenital uterine, tubal, and cervical anomalies
associated with exposure. Furthermore, some abnormalities may
promote other infertility factors. For instance, cervical anomalies may promote production of suboptimal cervical mucus,
or cervical stenosis may promote retrograde menstruation and
the subsequent development of endometriosis. Indeed, a recent
large prospective cohort study of patients with laparoscopically
confirmed disease identified a significantly elevated risk (RR 1.8,
CI 1.2–2.8) ofendometriosis amongwomenexposed to DES.[70]
Figure 7.2.6. Ultrasound demonstrating intrauterine adhesion. The
uterus is imaged in the longitudinal plane. Note the break in the
endometrial echo (arrow) consistent with an adhesion. The patient
subsequently underwent hysteroscopic lysis of the adhesional band.
Figure 7.2.7. Lysis of central intrauterine adhesion (imaged in Figure
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7.2.6) during office hysteroscopy.
Overall, when a DES-exposed woman has uterine anomalies on
HSG and greater than1 to 2 years ofprimary infertility,her prognosis forfuture pregnancy is extremely poor.[71] Metroplasty for
correction of T-shaped and hypoplastic DES-exposed uteri has
unprovenvalueandis not routinely recommended. Resultsof IVF
treatment are somewhat compromised in infertile DES-exposed
women. Although ovarian response rates to COH are comparable in DES-exposed women and nonexposed women with unexplained infertility, DES exposure is associated with significantly
lower implantation rates in IVF.[72] In the United States, DES
was bannedin 1971, andthe identification of the aforementioned
sequelae is becoming increasingly rareasaffectedwomenadvance
beyond reproductive age.
CONCLUSIONS
Given the prevalence of intrauterine abnormalities, the accurate
assessment of the endometrial cavity is of vital importance in the
work-up of the patient with infertility. The clinician’s armamentarium of approaches to this assessment includes both radiologic
and endoscopic studies. The choice of which modality to employ
is dependent on several variables, including accessibility, reliability, and cost. The patient history may provide information that
heightens the probability of a particular type of lesion, and the
sensitivity profile of the various imaging modalities for this type
of lesion may favor a particular approach. Transvaginal ultrasound provides a readily available initial screening of the uterus
and ovaries. HSG affords visualization of intracavitary lesions
Assessment of the Endometrial Cavity in the Patient with Infertility — 103
as well as functional assessment of the fallopian tubes. Sonohysterography and hysteroscopy provide excellent visualization of
endometrial pathology, with office hysteroscopy allowing intervention for some types of lesions in the same setting. A thorough
understanding of the endometrial pathologies that can impair
fertility can optimize the approach to the patient presenting with
infertility.
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Section 7.3. Ultrasound Oocyte Retrieval
https://t.me/med1917
Rosa Moghadam and Salli Tazuke
Since the birth of the first IVF baby in 1978 [1], IVF and related
assisted reproductive technologies (ARTs) are increasingly used
to overcome all types of infertility disorders. More than 48,000
infants were born from ART treatments in 2003, representing
more than 1% of the U.S. birth cohort.[2] With steady improvements in outcomes, ART has become the primary treatment
modality for several clinical diagnoses, such as tubal factor and
severe male factor infertility. Furthermore, ART has become an
excellent option for any patient who has exhausted less complex
treatment modalities and who has competent oocytes, spermatozoa, and a normal uterine cavity.
HISTORY
The history of IVF/ARTactuallydatesbackto1890, whenSchenck
achieved fertilization of donor rabbit oocytes in vitro and then
Heape transferred the embryos to a recipient rabbit.[3] Success in other mammalian models was not reported further until
1969, when Chang reported a successful in vitro fertilization and
intrauterine embryo transfer in mouse.[4] The application in
humans was first reported by Edwards in 1966 when oocytes
were successfully retrieved by mini-laparotomy and matured in
vitro.[5,6] As oocyte yield during the natural cycle was low, initially the focus was on developing the retrieval procedures via
operative laparoscopy. During the 1970s, because of the ability to obtain a magnified view of the ovary, laparoscopic egg
recovery had higher recovery rates, up to 33% to 45% [7,8],
and finally culminated in in vitro fertilization of human oocytes
and pregnancy in 1978 by Steptoe and Edwards.[1] Successful laparoscopic oocyte harvest, however, requires visual access
to the majority of the ovarian surface area and could not be
used in the setting of significant pelvic or ovarian adhesions.
The ultrasound-guided method of oocyte retrieval was developed by Lenz and Lauritsen [9] from Denmark in 1981 for
patients whose ovaries were inaccessible by the laparoscopic
approach. The success rate, however, was much lower than that
of the laparoscopic method initially.[10] Initially, transabdominal or endovaginal ultrasound was performed while the aspirating needle was introduced into the ovary via the percutaneous–
transvesical, transurethral–transvesical, or transvaginal route.
Subsequent to the development of the modern-day endovaginal transducer, which allowed clear visualization of the ovarian follicles, transvaginal oocyte retrieval by inserting a needle
through the vaginal fornices into the pelvic cavity has become
the dominant approach since the initial report in 1983 by Gleicher.[11,12] Transvaginal ultrasound–guided oocyte harvest is
not only less invasive compared with the laparoscopic approach
but also has been associated with a higher IVF rate, possibly by
limiting exposure to the toxic effect of general anesthesia or carbon dioxide pneumoperitoneum on the ova.[13,14] Onthe other
hand, the reproductive endocrinology andinfertility (REI) physician should be familiar with the laparoscopic approach to oocyte
harvest so that even patients with ovaries in an unusual position
can have optimal oocyte recovery.
In this section, we first present an overview of indications,
patient assessment, and ovarian stimulation protocols for IVF
and then follow with a detailed description of the transvaginal
oocyte retrieval procedure.
Patient Assessment and Ovarian Stimulation for ART
Once the decision to move to ART treatment has been made,
another decision needs to be made regarding how the patient’s
cycle will be best managed: what dose of gonadotropin will be
given and how premature LH surges will be prevented. Pretreatment assessment of ovarian reserve and gonadotropin responsiveness, together with the patient’s age, provides a basis for
deciding on a stimulation protocol.[15] The most commonly
used biochemical marker for ovarian function testing has been
the basal serum FSH on cycle day 2 or 3. Basal FSH level is an
indirect estimate of ovarian reserve and depends on an intact
hypothalamic–pituitary axis. However, a recent meta-analysis on
the performance of basal FSH level in the prediction of poor
ovarian response and failure to become pregnant after IVF concluded that clinical application of basal FSH is appropriate only
in patients with very elevated FSH.[16,17] Inhibin B is another
marker, secreted mainly by granulosa cells of the preantral ovarian follicles, and is thought to reflect the size of the ovarian
follicular pool.[18] During the menopausal transition, women
with elevated levels of FSH have significantly lower levels of
inhibin B comparedwith those with normal levelsof FSH.[19,20]
Decreased inhibin B was also found in women with normal FSH
levels, suggesting that changes in inhibin B levels may precede
elevation in FSH levels.[21] Antimullerian hormone (AMH), a
member of the transforming growth factor-β family, is a newer
biomarker produced by granulosa cells from primordial follicles.
The function of AMH in adult ovaries is hypothesized to inhibit
the recruitment of primordial follicles into the pool of growing
follicles.[22] AMH levels show a progressive decrease with age
[23], supporting the notion that AMH levels correlate directly
with the size of the available follicle pool in the ovary.SerumAMH
levels fluctuate minimally during the menstrual cycle [23,24],
which makes it more convenient to be used as a biomarker of
ovarian reserve. Use of serum AMH levels to predict success
with IVF treatments needs further validation. Ultrasound-based
106
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