A call for deeper insights into intramural pregnancy: An international data registry

Abstract

Intramural pregnancy (IMP) is a rare and potentially life‐threatening uterine ectopic pregnancy implanted within the myometrium. Despite its recognition as a distinct clinical entity, diagnostic challenges and a lack of standardized management protocols persist. IMP occurs when a gestational sac implants into the myometrium beyond the endometrial‐myometrial junction, often following uterine trauma. Diagnosis is hindered by non‐specific symptoms and frequent misclassification. While ultrasound is the primary diagnostic tool, magnetic resonance imaging (MRI) may be needed in unclear cases. Treatment options range from expectant management to surgical intervention, but no consensus exists on the optimal approach. To enhance understanding and improve clinical outcomes, we propose an international IMP registry to collect data on diagnosis, treatment, and fertility outcomes. This collaborative effort aims to inform evidence‐based guidelines, facilitating accurate early diagnosis and optimized patient care.

Abbreviations

EMJ

endometrial‐myometrial junction

IMP

intramural pregnancy

MRI

magnetic resonance imaging

Key message.

Intramural pregnancy (IMP) is a rare, potentially life‐threatening uterine ectopic pregnancy with diagnostic challenges and no standardized treatment. We propose an international data registry to collect all cases of IMP to enable the development of evidence‐based guidelines and enhance patient care.

Intramural pregnancy (IMP) was first identified in 1913 by Doederlein et al. as a “new type” of ectopic pregnancy, implanted within adenomyotic myometrial tissue. ¹ It was subsequently grouped under the classification of “uterine ectopic pregnancy” in 2020. ² Despite its significant risks to maternal health, including morbidity and mortality, progress in understanding and managing IMP over the past century has been slow, and standardized diagnostic or treatment protocols are lacking.

1. PATHOPHYSIOLOGY OF IMP

IMP is characterized by implantation within the uterine corpus, above the internal cervical os, and distinctly separate from the interstitial portions of the fallopian tubes, with the key morphological feature being implantation beyond the endometrial‐myometrial junction (EMJ). ² The etiology is not fully understood but always involves a breach of the EMJ, which allows implantation within the myometrium. This breach is often associated with prior uterine trauma; in the largest case series, 78% of IMP patients had a history of uterine surgery. ³ Dilatation and curettage is the most frequently reported risk factor, followed by salpingectomy and assisted reproduction techniques such as embryo transfer. ⁴ , ⁵ , ⁶ Other contributing factors include uterine abnormalities such as adenomyosis and fibroids, which can disrupt uterine architecture and facilitate abnormal implantation. ⁶ , ⁷ , ⁸ , ⁹

While the link with procedures that may naturally disrupt or iatrogenically injure the EMJ can be understood as risk factors, the underlying pathophysiology of a potential link between IMP and procedures such as salpingectomy remains unclear. Furthermore, while most IMP cases are linked to primary or secondary EMJ disruption, 22%–29% occur without identifiable risk factors. ³ , ⁸

2. PREVALENCE OF IMP

IMP is a rare form of uterine ectopic pregnancy, with approximately 100 cases reported in the literature to date. ³ , ⁴ This low number likely reflects the challenge of diagnosis rather than true prevalence, which remains unclear. Most early pregnancy providers lack experience with IMP, and this in combination with nonspecific symptoms probably contributes to the underdiagnosis, misdiagnosis, and underreporting.

3. DIAGNOSIS OF IMP

In 2020, the European Society of Human Reproduction and Embryology formally recognized IMP as a distinct clinical entity, separate from cervical and cesarean scar ectopic pregnancies. ² Diagnostic criteria require the pregnancy, whether that is a gestational sac or a heterogenous mass, to be located within the uterine corpus and breaching the EMJ. The pregnancy should be located above the internal cervical os, which helps to differentiate it from cervical ectopic pregnancies and cesarean scar ectopic pregnancies. It also must be separate from the interstitial portion of the fallopian tube to exclude interstitial pregnancy. Adopting these sonographic criteria should improve diagnostic accuracy and facilitate differential diagnosis from other types of uterine ectopic pregnancies.

As with all uterine ectopic pregnancies, IMP can be classified as partial or complete. Partial IMPs retain some communication with the uterine cavity, whereas complete IMPs are entirely enclosed within the myometrium, posing a higher risk of uterine rupture and hemorrhage. ² This distinction aids in clinical decision‐making and prognosis. Nevertheless, literature inconsistently describes IMP as implanted within the myometrium with “no connection” to the uterine cavity, potentially leading to misdiagnoses of partial IMPs as correctly sited eutopic pregnancies if the EMJ breach is overlooked. ¹⁰ , ¹¹ This is especially concerning in later gestations, where partial IMPs protrude predominantly into the uterine cavity. IMP has also been misdiagnosed, potentially because of operator unfamiliarity with the condition, as gestational trophoblastic disease, adenomyotic cysts, or degenerating fibroids. ³ , ⁴

Alternative diagnostic frameworks have been proposed. Luo et al. classified IMP into gestational cyst, mass, and uterine rupture types based on ultrasound findings, ¹² while others introduced a “rare variant” called subserosal pregnancy, where the gestational sac reaches the outer myometrium and is thus partially enclosed by uterine serosa. ¹³ However, all these pregnancies are primarily located within the myometrium, and they could all be classified as IMPs. The relation to the uterine serosa depends on the size of pregnancy, and if live IMPs were untreated and allowed to progress, the majority of them would eventually grow large enough to reach the uterine serosa and potentially end up rupturing. In view of that, the subserosal location of pregnancy is determined by their size rather than by their specific anatomical location. Therefore, we think that they should be classified as partial or complete along with the rest of IMPs and in accordance with the European Society of Human Reproduction and Embryology classification to ensure the use of a standardized approach and terminology that is applicable to all uterine ectopic pregnancies. Having a uniform and comprehensive classification system should help clinicians to offer an optimal treatment approach to all patients diagnosed with ectopic pregnancies and facilitate research in this area of practice.

Ultrasound remains the primary diagnostic modality of choice for IMP, with transvaginal two‐dimensional ultrasound used as standard. Three‐dimensional transvaginal ultrasound, with its multiplanar capabilities, offers enhanced visualization of the EMJ and uterine architecture, aiding differentiation between IMP and uterine pathologies such as adenomyosis. ¹⁴ , ¹⁵ Additionally, three‐dimensional imaging may offer advantages over two‐dimensional imaging by more precisely assessing whether the fallopian tube interstitial line is displaced rather than interrupted by the pregnancy—a key distinction in differentiating IMP from interstitial pregnancy. ¹⁶ , ¹⁷

Reported ultrasound diagnostic accuracy for IMP varies widely, ranging from 35% to 100%, with authors reporting reliance on additional modalities such as MRI, diagnostic laparoscopy, or even exploratory laparotomy to confirm diagnosis. ³ , ⁴ A recent review noted a 20% misclassification rate, with IMP frequently mistaken for an “angular,” “cornual,” or “interstitial pregnancy.” ⁴ The authors did not specify use of a reference standard for confirming IMP but reported using various modalities, including transvaginal ultrasound, three‐dimensional transvaginal ultrasound, contrast‐enhanced ultrasound, MRI, computed tomography, laparoscopy, laparotomy, and pathology to confirm the diagnosis.

A reference standard for confirming IMP is yet to be defined. While histology and surgery can be confirmatory, they are not universally applicable, as not all IMP cases are managed surgically, and histology mainly functions to confirm the presence of pregnancy tissue within the myometrium in hysterectomy specimens and to exclude gestational trophoblastic disease. Ultrasound could serve as a reference standard but achieving this requires agreement on standardized diagnostic criteria to improve its overall accuracy.

MRI has been highlighted as a useful adjunct for its multiplanar imaging and ability to differentiate IMP from other myometrial abnormalities. ¹⁴ , ¹⁸ , ¹⁹ However, it is typically reserved for when ultrasound findings are inconclusive, with one review reporting that MRI was required to diagnose IMP in 22% of cases. ⁴ More invasive modalities such as computed tomography, diagnostic laparoscopy and hysteroscopy have also been utilized, ⁴ but lack evidence of superiority over ultrasound.

These findings underscore the challenges of diagnosing IMP and the urgent need for standardized diagnostic protocols to improve reliability and outcomes.

4. NATURAL HISTORY OF IMP

The natural history of IMP is poorly understood, as most cases are managed medically or surgically, with only a small number managed expectantly. Given the apparent etiological similarities between IMP and cesarean scar ectopic pregnancies, it is plausible that progression of a viable partial IMP would also substantially increase the risk of maternal morbidity. Women should therefore be counseled about complications, including placenta accreta spectrum disorders, uterine rupture, severe hemorrhage, and need for emergency hysterectomy. To date, only two known cases of IMP have resulted in live births, both requiring emergency cesarean hysterectomy due to hemorrhage and uterine rupture at 30 and 37 weeks, respectively. ²⁰ , ²¹ In these cases, IMPs were not detected antenatally and the diagnosis was only made following histopathological examination of the uterus. The risk of uterine rupture requiring emergency surgery in IMP cases is estimated at 6%–15%. ³ , ⁴ The limited understanding of IMP's natural history complicates evidence‐based counseling for women considering continuation of their pregnancies.

5. MANAGEMENT OF IMP

Currently, there is no standardized treatment protocol for IMP, and various approaches have been employed, including expectant management, medical treatment (local ¹⁹ or systemic ¹⁰ , ¹⁷ methotrexate, potassium chloride injection ¹⁹ ), surgical interventions (transcervical suction curettage, ³ resection via laparoscopic, ¹⁰ , ²² laparotomy, ¹¹ , ¹⁴ , ¹⁷ hysteroscopic routes, ²³ or hysterectomy ¹¹ ), and other modalities such as uterine artery embolization. ²⁴ The hysterectomy rate has been reported as 13%, and medical management alone has a high failure rate, with 32% requiring subsequent surgery. ⁴ Despite American Society for Maternal‐Fetal Medicine guidelines advising against systemic methotrexate for cesarean scar ectopic pregnancies, it continues to be used for IMP. ²⁵

Success rates for expectant management vary widely. One study found a 75% success rate for expectant management in 44% of cases, ³ while another reported a 4% success rate. ⁴ Despite these mixed results, expectant management may be a viable option, especially for complete failing IMPs.

Given the diverse treatment options and their varying success, the optimal management strategy remains unclear. Treatment decisions are influenced by factors such as implantation site, gestational age, pregnancy viability, symptom severity, clinician expertise, available resources, and patient preferences, particularly regarding future fertility.

6. WHY IS AN INTERNATIONAL REGISTRY NEEDED?

Despite recognition within the gynecological community that IMP is linked to significant maternal and fetal morbidity, there is no standardized approach to its diagnosis or management. Our understanding remains limited, mainly due to the absence of comprehensive data on its natural history, and this complicates patient counseling. Most evidence comes from isolated case reports and small retrospective studies, resulting in significant variability in clinical management. The rarity of IMP further hinders consensus on optimal treatment strategies.

To address these challenges, we propose establishment of an international IMP data registry. We invite healthcare professionals to contribute IMP cases via www.medscinet.com/impregistry (Figure 1). This collaborative effort will provide essential insights to develop evidence‐based guidelines, improving diagnosis, management, and care for IMP patients.

FIGURE 1.

QR code to access intramural pregnancy registry.

7. INTRODUCING THE GLOBAL REGISTRY FOR INTRAMURAL PREGNANCY

The global registry for IMP is an international initiative to collect prospective data on IMP cases. It will focus on gathering information on obstetric and gynecological histories, diagnostic sonographic criteria (including ultrasound images and videos), disease progression, and management outcomes, alongside the impact on future fertility and pregnancy outcomes. Developed in partnership with OMDA MedSciNet, a company specialized in international medical databases, the registry will ensure anonymized and secure data storage.

The goal is to build a global dataset over an initial five‐year period, through 2030, to study the etiology, diagnosis, treatment complications, and natural history of IMP. Given its rarity, long‐term data collection is essential, with potential funding to extend beyond 2030. By consolidating global cases, the registry will offer critical insights to inform clinical guidelines and improve outcomes for this poorly understood condition.

AUTHOR CONTRIBUTIONS

DJ and SN conceived the idea. SN wrote the draft paper with support from all co‐authors. CB and DJ edited and provided critical input to improve the paper.

FUNDING INFORMATION

We gratefully acknowledge the generous donation from Miss Kelly Mobey and her family, which has been instrumental in funding the design and operation of the IMP registry.

CONFLICT OF INTEREST STATEMENT

The authors report no conflict of interest.

Nijjar S, Bottomley C, Jurkovic D. A call for deeper insights into intramural pregnancy: An international data registry. Acta Obstet Gynecol Scand. 2025;104:1420‐1423. doi: 10.1111/aogs.70007

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.