Radiological imaging of female infertility.

Dr/ ABD ALLAH NAZEER. MD.

Infertility.Infertility is defined as failure to conceive a desired pregnancy after 24 months of unprotected sexual intercourse.Approximate 10% of couple are infertile.Male and female are equally affected. Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy. Infertility may be caused by infection in the man or woman, but often there is no obvious underlying cause.

Imaging plays a key role in the diagnostic evaluation of women forinfertility. The pelvic causes of female infertility are varied and rangefrom tubal and peritubal abnormalities to uterine, cervical, and ovariandisorders. In most cases, the imaging work-up begins with hysterosalpingography to evaluate fallopian tube patency. Uterine fillingdefects and contour abnormalities may be discovered at hysterosalpingography but typically require further characterization with hysterographic or pelvic ultrasonography (US) or pelvic magnetic resonance (MR) imaging. Hysterographic US helps differentiate among uterine synechiae, endometrial polyps, and submucosal leiomyomas.Pelvic US and MR imaging help further differentiate among uterineleiomyomas, adenomyosis, and the various müllerian duct anomalies,with MR imaging being the most sensitive modality for detecting endometriosis. The presence of cervical disease may be inferred initiallyon the basis of difficulty or failure of cervical cannulation at hysterosalpingography. Ovarian abnormalities are usually detected at US. The appropriate selection of imaging modalities and accurate characterization of the various pelvic causes of infertility are essential because the imaging findings help direct subsequent patient care.

A systematic multimodalities imaging approach is advocated in which initial hysterosalpingography is followed by hysterographic US pelvic US, pelvic MRI or a combination with a selection of modalities depending on the finding on hysterosalpingography.An imaging study to evaluate female infertility and uterine anomalies should necessary exhibit many characteristic .1- Non-invasive.2- Low cost.3- High accuracy.

Causes of infertility.Uterine causes: Congenital anomalies, infections, uterine synechiae, focal lesions, intra-uterine scar, cervical stenosis, reduced uterine perfusion, alteration of the endometrium thickness and vascularity.Ovarian causes: Follicular and ovulation abnormalities, stromal vascularity ad endometriosis.Tubal causes: Infection and obstruction. Hormonal Problems : These are the most common causes of anovulation. The process of ovulation depends upon a complex balance of hormones and their interactions to be successful, and any disruption in this process can hinder ovulation. There are three main sources causing this problem.

Imaging modalities of infertilityIn most cases, the imaging work-up begins with hysterosalpingography to evaluate fallopian tube patency. Uterine filling defects and contour abnormalities may be discovered at hysterosalpingography but typically require further characterization with hysterographic or pelvic ultrasonography (US) or pelvic magnetic resonance (MR) imaging. Hysterographic US helps differentiate among uterine synechiae, endometrial polyps, and submucosal leiomyomas. Pelvic US and MR imaging help further differentiate among uterine leiomyomas, adenomyosis, and the various müllerian duct anomalies, with MR imaging being the most sensitive modality for detecting endometriosis. The presence of cervical disease may be inferred initially on the basis of difficulty or failure of cervical cannulation at hysterosalpingography. Ovarian abnormalities are usually detected at US. The appropriate selection of imaging modalities and accurate characterization of the various pelvic causes of infertility are essential because the imaging findings help direct subsequent patient care.

Hysterosalpingography (HSG) is a radiological procedure used to demonstrate the uterine cavity and the fallopian tube lumens using contrast medium. It is a valuable technique in the evaluation of an infertile female patient. Despite the development of other diagnostic tools, such as, magnetic resonance imaging, hysteroscopy, and laparoscopy; it remains the main examination for the fallopian tubes in developing countries.HSG, uses fluoroscopic control to introduce radiographic contrast material into the uterine cavity and fallopian tubes.Cycle consideration: HSG should not be performed if there is a possibility of a normal intra-uterine pregnancy.

Fallopian Tube Abnormalities.Fallopian tube abnormalities are the most common cause of female infertility, accounting for 30%–40% of cases. Hysterosalpingography provides optimal depiction of the fallopian tubes, allowing detection of tubal patency, tubal occlusion, tubal irregularity, and peritubal disease. If there is evidence of occlusion due to endometriosis, hysterosalpingography should be followed by MR imaging. A process diagram for diagnostic imaging of fallopian tube abnormalities.

Left hydrosalpinx. Hysterosalpingogram shows dilatation of the left fallopian tube (arrow) with an absence of contrast material outflow, findings indicative of tubal occlusion, and a patent normal right tube (arrowhead) with outflow of contrast material.

Tubal irregularity due to salpingitis isthmica nodosa. Spot (a) and magnified (b) views from hysterosalpingography depict multiple contrast material–filled luminal pouches (arrowheads) projecting 2–3 mm outward from the isthmic portion of both fallopian tubes.

Right peritubal pelvic adhesion due to previous pelvic inflammatory disease. Early (a) and late (b) hysterosalpingograms show normal contrast material filling of the right fallopian tube (arrow in a) and a rounded collection of leaked contrast material (arrowheads in b) adjacent to the ampullary portion of the right tube. The collection was due to peritubal adhesions. The left fallopian tube appears normal and patent.

Asherman syndrome in a patient with a history of dilation and curettage. (a) Hysterosalpingogram depicts several linear intrauterine filling defects (arrowheads). (b) Sagittal image from transvaginal hysterographic US shows multiple uterine synechiae (arrows).

Endometrial polyp. (a) Hysterosalpingogram depicts a well-circumscribed ovoid intrauterine filling defect (arrow). (b, c) Sagittal gray-scale (b) and color Doppler (c) US images from subsequent transvaginal hysterographic US show a posterior fundal endometrial polyp (arrowheads in b) with a central feeding vessel (arrow in c).

DES-related uterine anomaly. Hysterosalpingogram demonstrates a hypoplastic T-shaped uterus. The patient

had been exposed to DES while in utero.

Adenomyosis. Left posterior oblique hysterosalpingogram shows characteristic saccular contrast material collections (arrowheads) protruding beyond the normal contour of the endometrial cavity.

Submucosal leiomyomas. (16) Hysterosalpingogram shows a large intrauterine filling defect (arrows) due to a large submucosal leiomyoma that produces a mass effect on almost the entire uterus. (17) Axial T2-weighted MR image demonstrates a region of heterogeneous increased signal intensity that represents a fundal intramural fibroid (arrow) with a submucosal component (arrowheads). Nabothian cysts are visible in the cervix.

Sonohysterography and sonohysterosalpingography.Used to evaluate uterine pathology because of its excellent diagnostic accuracy, minimal patient discomfort, low cost and wide -spread availability.With the addition of transvaginal sonography, color Doppler imaging, and sonohysterography, Ultrasound has become a sensitive technique for detecting endometrial and myometrial pathology.During the excretory phase of the menstrual cycle, when the endometrial thickness ad the echo complex are better characterized.For congenital anomaly evaluation, the timing of the sonography examination is not critical.It involve airless, sterile, saline infusion through a soft plastic catheter in the cervix with simultaneous endovaginal US. It allow excellent visualization of the endometrial cavity and its lining.The procedure can also confirms tubal patency by demonstrating spillage of saline from a distended tube into pelvic cavity.

MRI.MR imaging is the best imaging modalities for delineating the morphology and orientation of the pelvic structures.Detects pathological lesions like adenomyosis, endometriosis and leiomyoma.Detect tubal lesions, Müllerian duct abnormality and ovarian pathology.Detect extra-pelvic causes like pituitary adenoma.MR imaging is often used as a problem solving modality when sonography finding are inconclusive.Limitations:Higher cost, limited availability and longer scanning time.

EndometriosisAn estimated 30%–50% of women with endometriosis are infertile, and 20% of infertile women have endometriosis, a condition defined by the presence of endometrial glands and stroma outside the uterus The US features of endometriosis are variable; US has low sensitivity for the detection of focal implants, but it may depict endometriomas . Endometriomas have a variable appearance, with the most specific US signs being an adenxial mass with faint internal echoes and highly echogenic mural foci . They generally occur within the ovary, often bilaterally. The sensitivity and specificity of MR imaging for the identification of endometriosis are higher (71% and 82%, respectively) than those of US . MR imaging features of endometriosis include cystic masses with thickened walls and loss of the interface between the lesion and adjacent organs. The masses have internal high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Other high signal- intensity features seen on T1-weighted images may include hydrosalpinx (the luminal contents of which may include blood products) and endometrial implants . However, the sensitivity (13%) of MR imaging for the detection of endometrial implants is low . For this reason, MR imaging alone cannot take the place of laparoscopy for the definitive diagnosis of endometriosis.

Endometrioma. Sagittal transvaginal US image obtained in a woman with a history of endometriosis shows an

ovarian mass with multiple fine internal echoes (arrows) and several hyperechoic mural foci (arrowheads).

Endometriosis. Unenhanced axial T1- weighted fat-suppressed MR image shows dilatation of the right fallopian tube (arrow) with internal high

signal intensity due to blood products, findings indicative of hematosalpinx. Smaller high-signal-intensity foci along the posterior uterine serosa (arrowhead) are indicative of endometrial implants.

Ovarian AbnormalitiesOvarian causes of infertility include primary conditions such as nonfunctional ovaries, premature ovarian failure, and absence of ovaries (gonadal dysgenesis). These conditions are usually diagnosed on the basis of clinical and biochemical findings. Imaging is more valuable for diagnosing the secondary ovarian causes of infertility, which include polycystic ovary syndrome, endometriosis, and ovarian cancer. Pelvic US is usually performed for initial evaluation of the ovaries. Polycystic ovary syndrome reportedly affects approximately 8% of women and may be one of the most common causes of female infertility . Women with this syndrome have hyperandrogenism, which leads to morphologic changes in the ovary, and elevated serum levels of luteinizing hormone . The overproduction of luteinizing hormone results in incomplete ovulatory cycles. Clinical manifestations of the condition include hirsutism, obesity, and oligoamenorrhea.

Polycystic ovary syndrome. (a) Transvaginal US image of the right ovary depicts multiple peripheral subcentimetric follicles (arrow). (b) Coronal T2-weighted MR image from the same patient shows bilateral ovarian enlargement with multiple peripheral follicles (arrows).

Müllerian Duct AnomaliesMüllerian duct anomalies are another potential cause of alteration in the normal uterine contour and, thus, of female infertility. It is estimated that approximately 1% of all women and 3% of women with recurrent pregnancy losses have a uterovaginal anomaly. As many as 25% of women with müllerian duct anomalies (compared with only 10% of the general population) have reproductive problems, including increased risk for spontaneous abortion, prematurity, intrauterine growth retardation, abnormal fetal lie, and dystocia at delivery. Accurate characterization of müllerian duct anomalies is essential because pregnancy outcomes and treatment options vary between the different classes of anomalies.

Class I: Uterine Hypoplasia and Agenesis: Hypoplasia and agenesis of the uterus and proximalvagina, which result from failed or incompletedevelopment of both müllerian ducts, account for5%–10% of müllerian duct anomalies. Patientsmay present with primary amenorrhea and often are initially evaluated with pelvic US or MR imaging, which reveals a small or absent uterus and proximal vagina. Mayer-Rokitansky-Küster- Hauser syndrome, the most common variant in this class of anomalies, is manifested by complete vaginal agenesis and, in most cases, uterine agenesis. The reproductive potential of patients with uterine hypoplasia is limited, and that of patients with uterine agenesis is absent.

Mayer-Rokitansky-Küster-Hauser syndrome in an 18-year-old female patient with primary amenorrhea. Sagittal T2-weighted MR image shows absence of the uterus, cervix, and proximal vagina, with an anomalous pelvic location of

the kidney (arrow). A remnant distal vagina (arrowheads) is seen.

Class II: Unicornuate Uterus.A unicornuate uterus is the result of failed or incomplete development of one of the müllerian ducts. Unicornuate uteri account for approximately 20% of all müllerian duct anomalies . Hysterosalpingography, US, and MR imaging characteristically reveal a laterally deviated, banana-shaped uterine horn with a single fallopian tube. In many cases, there is a rudimentary horn on the contralateral side, with or without an endometrial cavity that may or may not communicate with the dominant horn. Rudimentary horns are usually best visualized with MR imaging, which also readily demonstrates the absence of an endometrium in the rudimentary horn. Rudimentary horns with an endometrium often are resected because they are associated with an increased risk of endometriosis and a risk of pregnancy in the rudimentary horn.

Right unicornuate uterus. (21) Axial (a)and coronal oblique (b) T2-weighted MR images demonstrate a laterally deviated, banana-shaped right unicornuate uterus (arrow) with a non-cavitary rudimentary left horn (arrowhead in b). (22) Hysterosalpingogram shows opacification of a single right uterine cavity and a single right fallopian tube with contrast material spillover

Class III: Uterus Didelphys.A uterus didelphys (also known as didelphic uterus), which results from failed ductal fusion, is characterized by two symmetric, widely divergent uterine horns and two cervixes at hysterosalpingography, US, and MR imaging. Didelphic uteri account for approximately 11% of müllerian duct anomalies. MR imaging may be required to fully characterize the complex anomalies in this group. In approximately 75% of cases, a longitudinal vaginal septum is present, with or without a unilateral horizontal vaginal septum and resultant unilateral hematometrocolpos . Metroplasty may be performed in patients who have experienced recurrent spontaneous abortions or preterm deliveries, but the benefit of such surgery remains unclear.

Uterus didelphys. (a, b) Transverse transabdominal pelvic US image (a) and oblique axialT2-weighted MR image (b) demonstrate two divergent uterine horns (arrows) with distention of the right endometrial cavity (arrowheads in b). (c) Sagittal T1-weighted fat-suppressed MR image depicts high-signal-intensity material distending the right endometrial cavity and cervix (arrowheads), a finding indicative of right hematometrocolpos. An obstructive horizontal right vaginal septum was subsequentlyresected. (d) Coronal T2-weighted MR image demonstrates associated right renal agenesis.

Class IV: Bicornuate Uterus.Incomplete fusion of the müllerian ducts results in a bicornuate uterus, a condition that accounts for approximately 10% of uterine anomalies. In patients with this condition, hysterosalpingography shows two symmetric but divergent uterine horns. US and MR imaging may help confirm the presence of a bicornuate uterus by depicting a deep (> 1 cm) fundal cleft in the outer uterine contour and an intercornual distance of more than 4 cm. In some patients, US and MR imaging show two separate cervical canals; in such a case, the anomaly is characterized as bicornuate bicollis. A bicornuate bicollis uterus is distinguished from a uterus didelphys by a greater degree of myometrial fusion between the horns along the lower uterine segment. Patients with infertility related to a bicornuate uterus may undergo metroplasty to prevent recurrent second- and third-trimester pregnancy losses.

Bicornuate uterus. Oblique coronal T2-weighted MR image shows two symmetric uterine horns (arrowheads) with a deep fundal cleft (arrow). The low-signal-intensity change in the right endometrial

cavity is due to biopsy-proved endometrial carcinoma.

Class V: Septate Uterus.Partial or incomplete septal resorption after müllerian duct fusion results in a septate uterus, which is the most common uterine anomaly, accounting for approximately 55% of müllerian duct anomalies . Similar to a bicornuate uterus, a septate uterus has two cavities that are visible at hysterosalpingography. US and MR imaging may help differentiate a septate from a bicornuate uterus by depicting a normal convex, flat, or minimally concave (< 1-cm-deep) external fundal contour with a septate uterus . MR imaging also readily demonstrates the composition and extent of the septum: A fibrous septum is typically thin, with low signal intensity on T2-weighted images, whereas a muscular septum tends to be thicker, with intermediate signal intensity on T2-weighted images . Patients with a septate uterus have the poorest reproductive and obstetric outcomes, with spontaneous abortion rates ranging from 26% to 94%. A septectomy may be performed in those who have experienced recurrent spontaneous abortions. A fibrous septum can be resected hysteroscopically, whereas a muscular septum may require metroplasty

Septate uterus. (a, b) Oblique coronal T2-weighted MR images show a normal external uterine fundal contour (arrow in a) and a low-signal-intensity fibrous septum (arrowhead) that extends to the external cervical os (arrow in b). (c) Axial T2-weighted MR image shows septalextension into the vagina, with separate right and left vaginal canals (arrows).

Class VI: Arcuate Uterus. An arcuate uterus is the mildest anomaly and may be considered a normal variant. Near complete septal resorption results in a shallow, smooth, broad-based impression on the uterine cavity, which may be depicted at hysterosalpingography, US, and MR imaging. Observation of a normal outer uterine contour at US and MR imaging helps confirm the diagnosis.An arcuate uterus usually has no effect on fertility or obstetric outcomes.HSG of arcuate uterus may also show smooth indentation into the fundal cavity which cause saddle shaped appearance.

Arcuate uterus. Three-dimensional coronal US image (26) and coronal oblique T2-weighted MR image (27), obtained in different patients, show a smooth, broad-based, shallow endometrial impression (arrow) with a normal external contour of the uterine fundus (arrowhead).

Class VII: DES-related Uterine Anomalies. Between 1945 and 1970, DES was used for prevention of spontaneous abortions and treatment of hyperemesis gravidarum. Female fetuses exposed to DES in utero are at risk for developing a hypoplastic, irregular, T-shaped uterus and hypoplastic and strictured fallopian tubes, and they have an increased incidence of vaginal clear cell carcinoma later in life (38,39). In pregnant women who underwent in utero exposure to DES, the hypoplastic whom the presence of this condition is suspected may be assessed with a postcoital test that does not involve imaging.

DES-related uterine anomaly. Hysterosalpingogram demonstrates a hypoplastic T-shaped uterus. The patient had been exposed to DES while in utero.

Adenomyosis.Adenomyosis may be detected with various imaging modalities, including hysterosalpingography, US, and MR imaging. At hysterosalpingography, adenomyosis is identifiable with a finding of multiple linear or saccular contrast material collections that protrude beyond the normal contour of the endometrial cavity . The endometrial cavity may appear enlarged or distorted. US and MR imaging may be performed if the findings at hysterosalpingography are suggestive but inconclusive. US features of adenomyosis include globular uterine enlargement, heterogeneous myometrial echo texture The sensitivity of endovaginal US for detecting adenomyosis is 53%–89%, with a specificity of 67%–98%. MR imaging also is highly accurate for the diagnosis of adenomyosis and may be useful for problem solving. The reported sensitivity and specificity of pelvic MR imaging for the detection of adenomyosis are 78%–88% and 67%–93%, respectively. The diagnostic finding at MR imaging is diffuse or focal thickening of the junctional zone to more than 12 mm in association with low signal intensity on T2-weighted images. A junctional zone thickness of less than 8 mm virtually excludes the diagnosis, whereas a thickness of 8–12 mm requires additional investigation.

Adenomyosis. Sagittal transvaginal US image illustrates globular uterine enlargement with asymmetric thickening and heterogeneity of the myometrium (arrows) and poor definition of the endomyometrial junction (arrowheads). E = endometrium.

Adenomyosis. Sagittal T2-weighted MRimage shows high-signal-intensity foci (arrow) indicative of ectopic endometrial glandular implants with associated thickening of the junctional zone (> 12 mm) (arrowheads) due to smooth-muscle hypertrophy in a patient with focal anterior body adenomyosis.

Adenomyosis and leiomyoma. CoronalT2-weighted fat-saturated MR image depicts focal thickening of the junctional zone (arrowheads), which is a characteristic finding of focal adenomyosis, and an adjacent well-defined intramural leiomyoma (arrow) that produces a greater mass effect on the outer uterine contour.

LeiomyomasUterine leiomyomas are the most common benign pelvic mass lesions and the most common cause of uterine enlargement in non pregnant women (23). Leiomyomas may be found in any part of the uterus, in submucosal, intramural, and sub-serosal locations. They most often occur in multiples but also may occur singly. Infertility may result when leiomyomas are numerous or have submucosal or intra-cavitary locations that interfere with embryo transfer and implantation. In addition, patients with multiple leiomyomas are at an increased risk for early spontaneous fetal loss . A finding of uterine enlargement, distortion, or mass effect on the endometrial cavity on hysterosalpingograms is suggestive of uterine leiomyoma. If the lesion is located near the uterine cornua, it may obstruct the ipsilateral fallopian tube and thus cause a lack of tubal opacification.

Submucosal leiomyomas. (16) Hysterosalpingogram shows a large intrauterine filling defect (arrows) due to a large submucosal leiomyoma that produces a mass effect on almost the entire uterus. (17) Axial T2-weighted MR image demonstrates a region of heterogeneous increased signal intensity that represents a fundal intramural fibroid (arrow) with a submucosal component (arrowheads). Nabothian cysts are visible in the cervix.

Endocavitary leiomyoma. within and distending the endometrial cavity, a finding characteristic of an endocavitary leiomyoma. Several intramural fibroids (arrowheads) also are visible.

Cervical AbnormalitiesCervical Stenosis:The term cervical stenosis is clinically defined as cervical narrowing that prevents the insertion of a 2.5-mm-wide dilator . This condition may be congenital or secondary to infection or trauma.Risk factors include previous cone biopsy, cryotherapy, laser treatment, and biopsy for cervical dysplasia . The more severe the stenosis, the more likely it is to be symptomatic . Consequences of cervical stenosis include obstruction of menstrual flow with resulting amenorrhea, dysmenorrhea, and potential infertility due to inability of sperm to enter the upper genital tract . Cervical stenosis also may be a serious impediment to assisted fertility techniques including embryo transfer and intrauterine insemination. At hysterosalpingography, cervical stenosis may appear as narrowing of the endocervical canal (normal diameter, 0.5–3.0 cm), or it may manifest as complete obliteration of the cervical os, preventing insertion of the hysterosalpingographic catheter.

Conclusions.The pelvic causes of female infertility include tubal, peritoneal, uterine, endometrial, cervical, and ovarian abnormalities. A multimodality imaging approach may be useful for determining the cause of infertility and guiding clinical management in specific cases. An imaging evaluation for female infertility typically begins with an assessment of tubal patency at hysterosalpingography, which may be followed by pelvic US, pelvic MR imaging, or both to further characterize any additional findings (e.g., intrauterine filling defects or uterine contour abnormalities). Failure to cannulate the cervix at hysterosalpingography is suggestive of a cervical abnormality, whereas a normal hysterosalpingographic examination may point toward the possibility of an ovarian cause of infertility.

Process diagram shows a systematic approach to diagnostic imaging for female infertility. Findings from each imaging examination help determine whether further

examinations are needed and what modality or modalities would be most useful.

Thank You.