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Ultrasonography of pregnancy of unknown location

Ultrasonography of pregnancy of unknown location
Literature review current through: Jan 2024.
This topic last updated: Apr 19, 2023.

INTRODUCTION — Pelvic pain or vaginal bleeding during the first trimester of pregnancy is a common presentation to clinicians in the office or emergency department. Determining the location of the pregnancy is the first priority in the evaluation of these patients, with the exception of hemodynamic stability. Whether the pregnancy is intrauterine or ectopic (and the precise extrauterine location), and desired or undesired, guides the remainder of the evaluation and management. Early diagnosis of ectopic pregnancy is important to avoid adverse sequelae of this potentially life-threatening condition. Pelvic ultrasonography (US) is the most useful imaging modality for these patients.

Sonography of patients with pregnancy of unknown location will be reviewed here. Related topics are discussed in detail separately and include:

Evaluation and management of pregnancy of unknown location (see "Approach to the patient with pregnancy of unknown location")

Diagnosis of ectopic pregnancy (see "Ectopic pregnancy: Clinical manifestations and diagnosis")

Use of ultrasound examination in obstetrics and gynecology (see "Overview of ultrasound examination in obstetrics and gynecology")

Ultrasound measurements to calculate gestational age (see "Prenatal assessment of gestational age, date of delivery, and fetal weight")

ULTRASOUND VERSUS OTHER IMAGING MODALITIES — US is the pelvic/abdominal imaging modality of choice for pregnant patients. It does not require the use of potentially harmful ionizing radiation, is readily available, and allows real-time imaging. (See "Overview of ultrasound examination in obstetrics and gynecology".)

Magnetic resonance imaging (MRI) is useful if US is not able to elucidate the location of a pregnancy [1]. Examples of this include differentiating an intrauterine pregnancy from a cervical or interstitial pregnancy when visualization is made difficult by fibroids or patient body habitus, or in patients with an abdominal pregnancy or uterine duplication abnormalities. The performance of MRI can be superior to US, as it provides high soft tissue contrast in multiple planes with a larger field of view. MRI can be performed at any stage of pregnancy, though gadolinium-based contrast agents are typically avoided. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Magnetic resonance imaging'.)

Computed tomography generally has no role in the evaluation of pregnancy of unknown location, due both to its limited resolution of tissue planes and use of radiation.

ULTRASOUND TECHNIQUE

Transabdominal versus transvaginal — Transvaginal US (TVUS) is the principal approach used for sonographic evaluation of pregnancy of unknown location. TVUS allows for earlier and more reliable detection of an intrauterine or ectopic pregnancy (abdominal pregnancies are an exception) and is more sensitive for detecting embryonic cardiac activity at very early gestational ages compared with transabdominal US (TAUS) (image 1 and image 2) [2]. For the remainder of this review, the term "US" refers to TVUS if not otherwise specified.

TAUS is useful as an initial study since it allows for a larger field of view than transvaginal scanning. We start with a TAUS to get a general overview of the pelvic anatomy and also scan the upper abdomen. A low frequency transducer (typically 2 to 5 MHz) is used, which allows penetration through the anterior soft tissues. Imaging of the upper abdomen is used primarily to check for free fluid.

The next step is a TVUS, performed with a higher frequency transducer (typically 5 to 12 MHz). Since the area of interest is closer to the probe, less penetration is needed.

Doppler ultrasound — Doppler color flow US is of limited value in the diagnosis of ectopic pregnancy. Trophoblastic tissue has high velocity systolic flow and low impedance diastolic flow, characteristics that are highlighted with Doppler. However, the absence of a finding of color flow Doppler in a complex adnexal mass does not exclude an ectopic pregnancy [3]. In addition, color flow Doppler does not differentiate a tubal pregnancy from a corpus luteum, since a "ring of fire" appearance can be seen for either entity (image 3). (See 'Fallopian tubes' below.)

The primary contribution of Doppler in patients with pregnancy of unknown location is that it occasionally identifies an adnexal mass that was not detected on gray-scale US (image 4). In addition, Doppler US may aid in determining placental patterns of blood flow at ectopic sites, characterized by high velocity and low resistance [4,5]. However, this pattern is not diagnostic as it can also be seen with some corpus luteal cysts.

Three-dimensional ultrasound — Three-dimensional US provides views of the uterus that cannot be obtained with conventional two-dimensional US. It is typically not needed for diagnosis of ectopic pregnancy; however, it may be useful if the precise location of a pregnancy is unclear (eg, differentiating an interstitial from an angular pregnancy) [6-8]. It can also be helpful in providing information when there is an abnormal pregnancy occurring in the setting of a congenital uterine anomaly [9]. Although magnetic resonance imaging (MRI) performance may be superior to three-dimensional US, three-dimensional US should be performed, if available, prior to considering MRI.

ABSENCE OF FINDINGS — When a pregnant patient with pain and/or bleeding has an US that has no findings of pregnancy (ie, no intrauterine pregnancy [IUP], adnexal mass, or echogenic fluid in the pelvis), the differential diagnosis is normal early IUP, nonviable IUP, or ectopic pregnancy. Approximately 15 to 26 percent of patients with ectopic pregnancy will have a "normal" initial US [10-12].

Patients with a pregnancy of unknown location are often followed with serum human chorionic gonadotropin (hCG) levels and repeat US. The hCG is often positive before US can detect a pregnancy; thus, repeat US is performed either when the hCG level reaches the discriminatory zone for endometrial findings or in three to four days (sometimes sooner) since the gestational sac of an IUP grows approximately 1 mm per day and is visible on US when it reaches 3 mm or greater. In 11 to 16 percent of cases with an indeterminate initial scan, ectopic pregnancy is evident on follow-up US [13,14].This is discussed in detail separately. (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Detection of human chorionic gonadotropin' and "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'hCG discriminatory zone' and "Approach to the patient with pregnancy of unknown location", section on 'Subsequent testing in selected patients'.)

A patient with a pregnancy of unknown location and in whom the pregnancy is undesired may be able to forgo follow-up testing with hCG and US and undergo expedited active management (eg, diagnostic uterine aspiration [with laparoscopy if an adnexal mass is present]); this is discussed in detail elsewhere. (See "Approach to the patient with pregnancy of unknown location", section on 'Hemodynamically stable patients'.)

EARLY ENDOMETRIAL FINDINGS — During the first three to five weeks of pregnancy (conceptus phase), the endometrium has a "trilaminar" appearance. The first sonographic finding of either a normal or abnormal pregnancy is an endometrial fluid collection. As a pregnancy progresses, a yolk sac and embryo should eventually be visualized, which confirm the location of the pregnancy. (See 'Endometrial findings diagnostic of intrauterine pregnancy' below.)

Sonographic measurement of endometrial thickness has also been studied as a diagnostic test for ectopic pregnancy, but most investigators have not found it to be clinically useful [15-17].

Many patients develop pain and/or bleeding during early gestation, thus, it is important to identify characteristics of endometrial fluid collections associated with either intrauterine pregnancy (IUP) or ectopic pregnancy. Depending upon patient symptoms and hemodynamic status, management decisions often must be based upon this early information.

Intrauterine pregnancy — Findings consistent with a gestational sac are suggestive, but not diagnostic, of an IUP.

Gestational sac — The gestational sac of an early pregnancy may be distinguished from other intrauterine fluid collections (including an endometrial pseudosac) by the presence of the intradecidual sign and the double decidual sign. However, these signs were defined with use of transabdominal US (TAUS). With transvaginal US (TVUS), the intradecidual sign or double decidual sign are absent in at least 35 percent of gestational sacs [18,19]. (See 'Pseudosac' below and 'Decidual cyst' below.)

The presence of a gestational sac without a yolk sac and/or embryo at specific sac size thresholds is diagnostic of a pregnancy loss (image 5). (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

Intradecidual sign – The intradecidual sign is the earliest US finding associated with an IUP. On TVUS, this sign typically can be seen at approximately 4.5 weeks of gestation, when the human chorionic gonadotropin (hCG) is equal or greater than 1500 IU/L, and/or when the mean sac diameter (ie, the average measurement of the sac obtained in three planes) is 3 mm or greater [20].

The intradecidual sign is a small round fluid collection surrounded by an echogenic rim (image 6). It is eccentrically located within the endometrial cavity and should deviate the endometrial lining. This structure and its echogenic rim represent the chorionic cavity, implanting chorionic villi, and associated decidual tissue. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Gestational sac'.)

Detection of the intradecidual sign in a patient with first-trimester bleeding and/or pain is only partially reassuring since its sensitivity for detecting an IUP is 48 to 68 percent [20,21]. Further evaluation is needed for desired pregnancies to ensure an IUP and appropriate growth of the pregnancy.

Double decidual sac sign – The double decidual sign is visible at 4 to 6 weeks of gestation [21] until up to 9 weeks of gestation [22]. It is most helpful prior to 6 to 6.5 weeks of gestation, as an embryo is typically seen after that time. It consists of two concentric echogenic rings of tissue surrounding an intrauterine gestational sac (image 7). This sign is mostly useful for identifying an IUP using TAUS [22]. When the double decidual sac sign is seen on TAUS, a yolk sac can typically already be seen using TVUS.

Nonspecific findings

Pseudosac — Pseudosac (pseudogestational sac) is a small collection of fluid or blood that is centrally located within the endometrial cavity and is surrounded by a thick decidual reaction (image 8) [23]. Differentiation factors between a pseudosac and the intradecidual signs are that a pseudosac:

Does not have an echogenic rim

Tends to be located in the middle of the uterine cavity rather than embedded in the decidua

Can change in shape during the scan

May appear to be complex since it contains blood

The finding of a pseudosac is a nonspecific finding but is more consistent with an early IUP than an ectopic pregnancy. In a retrospective study of almost 650 patients with a positive serum hCG and an early US demonstrating only an intrauterine fluid collection (defined as an intrauterine saclike structure without a yolk sac or embryo and no extraovarian adnexal mass), subsequent sonograms demonstrated an IUP in all cases; no ectopic pregnancies were diagnosed [24]. At the end of the first trimester, 41 percent of these pregnancies were alive, and the remaining (59 percent) miscarried. In a subsequent retrospective study including patients with a pregnancy of unknown location and available for follow-up, more patients with an intrauterine collection were diagnosed with an intrauterine (363/789 patients, 46 percent) than an ectopic (8/162 patients, 4.9 percent) pregnancy [25].

Decidual cyst — Decidual cysts are small cysts within the endometrium that can be seen in either intrauterine or ectopic pregnancies [26]. Factors that differentiate these cysts from a gestational sac include that decidual cysts (image 9) [27]:

Tend to have a thinner wall

Do not abut the endometrial canal

Are generally located in the peripheral endometrium at the myometrial junction

Can be multiple

ENDOMETRIAL FINDINGS DIAGNOSTIC OF INTRAUTERINE PREGNANCY

Yolk sac — The yolk sac is a round fluid structure seen within the gestational sac [28]. The presence of a yolk sac within a gestational sac located in the endometrial cavity is diagnostic of an intrauterine pregnancy (IUP) but does not confirm viability. On transvaginal US (TVUS), the yolk sac is typically seen by approximately 5.5 weeks of gestation and should always be visible before the embryo is visible (image 2) [29].

Thus, in early pregnancy, when a yolk sac is not seen and an embryo is identified, an abnormal IUP is present. The yolk sac gradually decreases in size after the 10th week of gestation and is typically not visualized by the end of the first trimester. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

Embryo — The presence of an embryo within the endometrial cavity also confirms an IUP. An embryo is typically seen at approximately 6 to 6.5 weeks of gestation. A commonly used discriminatory criterion for visualization of an embryo on TVUS is a mean gestational sac diameter of 25 mm [30]. It should be noted that an embryo is typically seen in sacs much smaller than 25 mm. The 25 mm threshold is used in order to ensure that a normal pregnancy is not missed.

Embryonic cardiac activity is generally detected by the time the embryonic crown-rump length is 2 to 3 mm in size; if the crown-rump length is 7 mm or greater in size, without cardiac activity, it is a nonviable pregnancy [30]. As with gestational sac size, the 7 mm threshold is set high to avoid missing a normal pregnancy. Since cardiac activity is typically seen prior to this size, it is not a reassuring finding to see, for example, a 5 mm embryo without cardiac activity.

ADNEXAL FINDINGS — An extraovarian adnexal mass, seen in 89 to 100 percent of patients with ectopic pregnancy, is the most common US finding in tubal pregnancy [12,27,31].

Ovaries — In a patient with a pregnancy of unknown location, US of the ovaries is performed to differentiate the normal corpus luteum of pregnancy from a tubal or ovarian pregnancy. This distinction is simple when the corpus luteum has a thin, almost imperceptible wall and is clearly located within the ovary. However, when the corpus luteum is hemorrhagic with a thick wall or is exophytic, it can mimic the appearance of an ectopic pregnancy [32].

In challenging cases, the degree of echogenicity of an adnexal mass may help distinguish the tubal ring of an ectopic pregnancy from a corpus luteum (image 10) [33]. The corpus luteum is usually equal to or less echogenic than the ovary, while the tubal ring of an ectopic pregnancy is usually more echogenic than the ovarian parenchyma and endometrium, just as an intrauterine gestational sac is more echogenic than the endometrium.

A bimanual scanning technique can be used to determine whether the mass is separate from the ovary [34]. To perform this technique, one hand is on the transvaginal US probe, and the other hand applies gentle suprapubic pressure to move the uterus and adnexa. This technique can be helpful in the setting of an enlarged fibroid uterus when there is difficulty distinguishing ovaries and adnexal structures. If used, the pressure should be gentle to avoid rupturing an ectopic pregnancy.

It should be noted that the laterality of the corpus luteum has no significance regarding the potential side of tubal pregnancy. Implantation occurs contralateral from ovulation in up to one-third of tubal ectopic pregnancies [35].

Fallopian tubes — The fallopian tube is the site of 96 percent of all ectopic gestations; 75 to 80 percent of implantations occurring in the ampullary tubal segment (figure 1). Therefore, imaging will visualize most ectopic pregnancies between the uterus and ovary. (See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites".)

A range of sonographic adnexal findings can be seen in a tubal ectopic pregnancy. US confirmation of a tubal pregnancy is made when an extrauterine sac with a yolk sac and/or embryo is visualized. The embryo may or may not have cardiac activity, depending upon its gestational age and viability (image 11 and image 12). The finding of an embryo with cardiac activity in the adnexa is diagnostic of extrauterine pregnancy but has low sensitivity [36].

An adnexal finding that is suggestive, but not diagnostic, of a tubal pregnancy is a "tubal ring." This is an early finding, no yolk sac is seen. The fluid center represents the sac and the echogenic ring represents the trophoblastic tissue (image 13).

Commonly, a noncystic, extraovarian mass (image 14) is visualized. This is a nonspecific finding, and may represent either an ectopic pregnancy or another type of adnexal mass. A meta-analysis of 565 patients in 10 studies reported that using a sonographic finding of an adnexal mass other than a simple cyst or an intraovarian lesion for the diagnosis of a tubal pregnancy had a sensitivity of 84 percent and specificity of 99 percent [36].

Since some types of adnexal masses are long standing, an US with a nonspecific adnexal mass may be compared with prior studies to assess whether the mass was visualized previously and whether it has changed in appearance. In a patient without evidence of an intrauterine pregnancy, any type of new adnexal mass should be further evaluated until the location and status of the pregnancy have been confirmed.

PERITONEAL FREE FLUID — Echogenic peritoneal free fluid in a patient with a pregnancy of unknown location is associated with ectopic pregnancy.

A small amount of clear free fluid in the pelvis is a normal sonographic finding. There is no established threshold for the volume of fluid that is physiologic and the volume is difficult to measure sonographically. However, fluid that is anechoic and isolated to the pelvic cul-de-sac and adjacent recesses is likely physiologic [37]. Larger quantities of simple fluid are typically reflective of pathology, even if due to a ruptured simple ovarian cyst.

Echogenic or complex fluid is never physiologic, even when present in small quantities, and almost always represents hemoperitoneum (image 15) [13,14]. Alternatively, echogenic fluid may also be purulent. For example, patients with ruptured appendicitis with secondary abscess formation or tubo-ovarian abscess, can have focal, "walled-off" areas of echogenic complex fluid. This fluid appears more contained (rather than free intraperitoneal, as in the case of hemoperitoneum) and the clinical presentations of these patients are different from those with positive pregnancy test presenting for assessment for ectopic pregnancy. When echogenic fluid is seen in the pelvis, it is important to scan the upper abdomen around the liver, kidneys, and spleen, to assess for additional fluid (image 16). (See "Epidemiology, clinical manifestations, and diagnosis of tubo-ovarian abscess" and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis".)

Echogenic fluid in a pregnant patient with no evidence of an intrauterine pregnancy is worrisome for ectopic pregnancy. In a prospective study, the finding of echogenic fluid in pregnant patients with a pregnancy of unknown location had a sensitivity of 56 percent and specificity of 96 percent for predicting an ectopic pregnancy [10]. The main differential diagnosis for this finding is a ruptured hemorrhagic corpus luteal cyst. The presence of an adnexal mass with characteristics consistent with an ectopic gestation helps to clarify the diagnosis. (See 'Fallopian tubes' above.)

The presence or absence of peritoneal free fluid is not a reliable indicator of whether an ectopic pregnancy has ruptured [38,39]. This was illustrated in a retrospective study of 132 patients with tubal pregnancy who underwent transvaginal US prior to surgery. Among those found to have tubal rupture at the time of surgery, 21 percent had no fluid or trace peritoneal fluid on US. On the other hand, 37 percent of patients with large amounts of free fluid (defined as fluid present in the upper abdomen) on US had intact fallopian tubes at time of surgery [39].

Severe bleeding (ie, >300 mL) from either an ectopic pregnancy or a ruptured corpus luteal cyst requires immediate evaluation and treatment. (See "Tubal ectopic pregnancy: Surgical treatment" and "Approach to the patient with pregnancy of unknown location", section on 'Hemodynamically unstable patients' and "Evaluation and management of ruptured ovarian cyst", section on 'Patients with complicated cyst rupture'.)

SPECIAL ISSUES

Rare ectopic pregnancy locations — Although rare, ectopic pregnancy can occur in a nontubal location.

Interstitial pregnancy — An interstitial pregnancy is implanted in the interstitial portion of the fallopian tube, which is the proximal tubal segment embodied within the muscular wall of the uterus. Interstitial pregnancies may be misdiagnosed as intrauterine [40-42]. (See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites", section on 'Interstitial pregnancy'.)

The sonographic signs used to diagnose interstitial pregnancy are:

Eccentric location of the gestational sac proximal to the uterine cornua.

"Interstitial line," defined as an echogenic line that extends from the most superior and lateral aspect of the endometrium to the midportion of the interstitial mass or sac (image 17) [43].

Failure to see the myometrium completely surrounding the sac.

Failure of the sac to communicate with the endometrium.

The interstitial line likely represents either the endometrial canal or the interstitial portion of the fallopian tube, depending on the size of the gestation [43].

Among the signs used to diagnose interstitial pregnancy, data from small series suggest that the interstitial line is more useful than eccentric sac location or myometrial thinning [43,44].

The term interstitial pregnancy is often used interchangeably with cornual pregnancy, however, a cornual pregnancy specifically refers to a pregnancy in the horn of a bicornuate uterus.

The term angular pregnancy is seldom used. This refers to a pregnancy that extends beyond the interstitium into the lateral "angle" of the uterine cavity. This distinction is important since angular pregnancies, unlike interstitial pregnancies, are more likely to miscarry rather than rupture [45].

Ovarian pregnancy — Ovarian pregnancies are rare and their sonographic diagnosis can be very difficult [46,47]. An ovarian ectopic pregnancy can be mistaken for a corpus luteum, unless the gestational sac of an embryo is visualized surrounded by ovarian tissue. Laparoscopy and pathologic analysis are often necessary to make the diagnosis. Ovarian pregnancies can be confused for hemorrhagic cysts even at laparoscopy. Pathologic criteria developed by Spiegelberg to distinguish primary ovarian pregnancies from other ectopic pregnancies with secondary involvement of the ovary are as follows [48]:

(1) The fallopian tube on the involved side is intact and separate from the ovary.

(2) The gestational sac is in the normal position of the ovary.

(3) The ovary with the gestational sac is connected to the uterus by the ovarian ligament.

(4) The specimen has ovarian tissue attached to, and in, the wall of the gestation sac.

Heterotopic pregnancy — Patients who undergo in vitro fertilization (IVF) are at increased risk of heterotopic pregnancy compared with other pregnant patients. If an intrauterine pregnancy (IUP) is seen in a patient with pain and bleeding who has undergone IVF, the risk of also having an ectopic pregnancy is approximately 1 percent; this risk is similar to a patient who did not have IVF and has pain and bleeding and no IUP on US. Thus, even when US identifies an IUP in an IVF pregnancy, it is important to carefully survey potential ectopic gestation sites (eg, tube, ovary, cervix).

Sonographic signs suggestive of heterotopic pregnancy are the same as for any ectopic pregnancies (eg, complex adnexal mass, peritoneal free fluid).

The diagnosis and management of heterotopic pregnancy are discussed in detail separately. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Heterotopic pregnancy' and "Ectopic pregnancy: Choosing a treatment", section on 'Heterotopic pregnancy'.)

Other locations — Other potential ectopic or abnormally implanted intrauterine pregnancy sites are cervical, cesarean scar, and abdominal. Their sonographic diagnoses are discussed in detail separately. (See "Cervical pregnancy: Diagnosis and management" and "Cesarean scar pregnancy" and "Abdominal pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ectopic pregnancy" and "Society guideline links: Ultrasound imaging in pregnancy".)

SUMMARY AND RECOMMENDATIONS

Modality – Transvaginal pelvic ultrasonography (US) is the most useful imaging modality for patients with pregnancy of unknown location. (See 'Ultrasound versus other imaging modalities' above.)

Ultrasound findings

Absence of findings – For pregnant patient with an US that has no findings of pregnancy (ie, no intrauterine pregnancy [IUP], adnexal mass, or echogenic fluid in the pelvis), the differential diagnosis is a normal early IUP, nonviable IUP, or ectopic pregnancy. Approximately 15 to 26 percent of patients with ectopic pregnancy will have an initial US with no findings. (See 'Absence of findings' above.)

Gestational sac – Sonographic identification of an intrauterine gestational sac (image 5 and image 1) is suggestive, but not diagnostic, of an intrauterine pregnancy (IUP). (See 'Early endometrial findings' above.)

On transvaginal US (TVUS), a mean gestational sac diameter of >25 mm without an embryo is commonly used discriminatory criteria for diagnosis of miscarriage. (See 'Gestational sac' above.)

Yolk sac or embryo – The presence of a yolk sac (image 2) or an embryo within the endometrium is diagnostic of an IUP, but does not confirm viability. (See 'Endometrial findings diagnostic of intrauterine pregnancy' above.)

On TVUS, a crown-rump length of >7 mm without cardiac activity is commonly used discriminatory criteria for diagnosis of miscarriage. (See 'Embryo' above.)

Pseudo sac – The identification of centrally located endometrial fluid is a nonspecific US finding; which is more likely to represent an IUP rather than an ectopic pregnancy. (See 'Pseudosac' above.)

Adnexal findings – Adnexal findings that are suggestive, but not diagnostic, of a tubal pregnancy are a "tubal ring" or a noncystic adnexal mass. Sonographic confirmation of a tubal pregnancy is made when an extrauterine sac with a yolk sac and/or embryo is visualized. (See 'Adnexal findings' above.)

Peritoneal free fluid – Echogenic peritoneal free fluid in pregnant patients who present with pain and/or bleeding almost always represents hemoperitoneum (image 15 and image 16). The presence or absence of peritoneal free fluid is not a reliable indicator of whether an ectopic pregnancy has ruptured. (See 'Peritoneal free fluid' above.)

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Topic 5410 Version 27.0

References

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