case study on fibroid uterus

Case report

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• Published: 13 July 2021

Massive uterine fibroid: a diagnostic dilemma: a case report and review of the literature

• Wiesener Viva 1 ,
• Dhanawat Juhi   ORCID: orcid.org/0000-0002-4273-1376 1 , 2 ,
• Andresen Kristin 1 ,
• Mathiak Micaela 3 ,
• Both Marcus 4 ,
• Alkatout Ibrahim 1 &
• Bauerschlag Dirk 1  

Journal of Medical Case Reports volume  15 , Article number:  344 ( 2021 ) Cite this article

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Fibroids of the uterus are the most common benign pelvic tumors in women worldwide. Their diagnosis is usually not missed because of the widespread and well-established use of ultrasound in gynecological clinics. Hence, the development of an unusually large myoma is a rare event, particularly in first-world countries such as Germany. It is even more uncommon that a myoma is misdiagnosed as a dietary failure.

Case presentation

Herein, we report the case of a Caucasian woman with a giant fibroid that reached a size of over 50 cm, growing slowly over the past 15 years, and was misdiagnosed as abdominal fat due to weight gain. We aim to discuss the factors that lead to the growth of such a huge tumoral mass, including misdiagnosis and treatment, and the psychological impact. Through this case, we intend to increase the awareness among general physicians and gynecologists. Although menstrual disorders incorporate several pathologies, adequate assessment remains the primary responsibility of health care providers. A literature review revealed approximately 60 cases of giant uterine fibroids.

The use of clinical and diagnostic devices, especially ultrasound, in this case, is indispensable. In conclusion, the growth of a giant fibroid can have disastrous effects on a woman’s health, including surgical trauma and psychological issues.

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Introduction

Leiomyomas or fibroids are the most common benign pelvic tumors in females that grow monoclonally from the smooth muscle cells of the uterus. Such tumors occur in nearly half of women over the age of 35 years, with increased prevalence during the reproductive phase due to hormone-stimulated growth [ 1 ]. At 50 years of age, 80% of African and almost 70% of Caucasian women have fibroids [ 2 ]. As the underlying pathogenesis of the development of these tumors remains unclear, several risk factors, such as positive family history, genetic alterations, and lifestyle factors (smoking, obesity, dyslipidemia, nutrition, exercise, and medical contraception), have been identified. Treatment of these lifestyle-associated risk factors with vitamin D supplementation, statin use, and dietary modification appears to be protective, along with parity [ 1 , 3 ]. Myomas may occur as a single lesion or as multiple lesions as reported in two-third of the cases, with variation in size from microscopic to large macroscopic extent [ 1 , 4 ]. As the majority of women with myomas remain asymptomatic [ 2 ], the number of undiagnosed uterine fibroids is high. Symptomatic women most likely suffer from abnormal uterine bleeding (meno- or metrorrhagia and polymenorrhea) as well as dysmenorrhea. Other frequent symptoms include dyspareunia or chronic acyclic pelvic pain [ 3 ]. Fibroids affect fertility [ 5 ] and can have a severe psychological impact on a woman’s life [ 3 ]. With continued growth, myomas can cause compression-related symptoms, such as dyspnea, frequent urination, or bowel complaints. The growth rate of myomas varies intra- and interindividually, thereby regressing or gradually increasing in size until the climacteric period is possible [ 1 ]. The identification of rapidly progressing growing fibroids requires close observational ultrasound examinations. Extremely large myomas can involve serious complications such as respiratory failure due to diaphragmatic compression [ 6 ] or incarcerated abdominal wall hernia [ 7 ].

In Germany, universal access to healthcare services is guaranteed by law [ 8 ]. The German ambulatory care sector is densely structured with accessibility of general physicians in less than 30 minutes in more than 90% of all cases [ 9 ]. Utilization of gynecological services in Germany usually begins between the ages of 15 and 16 years [ 10 ] and continues at age 20 with annual visits for prevention of cervical carcinoma [ 11 ], followed by recurrent examinations for breast cancer prevention [ 12 ]. The self-reported prevalence of myomas is high in German women (8.0%), with a mean age of 33.5 years at diagnosis. After the USA, Germany has the second-highest hysterectomy rate among women with uterine fibroids (29.1% versus 21.8%) [ 3 ]. Although diagnosis of a giant myoma is difficult with several possible differential diagnoses, the majority of uterine myomas are confidently diagnosed in the (pre-)clinical routine [ 1 ]. Herein, we present a rare case of a German woman whose uterine tumor was misdiagnosed and remained untreated for the past 15 years, growing into a giant fibroid (16.4 kg) with a size over 50 cm.

A nulligravid, 46-year-old German woman presented to the gynecology clinic because of abnormal uterine bleeding and a slowly increasing abdominal extent in the past 15 years. She had no bowel or bladder complaints. The patient reported two episodes of polymenorrhea and menorrhagia in the past years. Due to the patient’s general fear of physicians and absence of frequent symptoms, she consulted her gynecologist and general physician sporadically. The gynecologist did not use ultrasound to clarify the uterine pathology. The general physician attributed her progressive abdominal extent to weight gain and advised dietary change and physical exercise as management. Both primary health care providers did not perform a thorough physical examination, including imaging methods, leaving the fibroid undiagnosed and untreated.

In our clinic, a preliminary physical examination was performed, which indicated good general condition and no evidence of pallor or pedal edema. The patient’s preoperative body mass index (BMI) was 32.1 kg/m 2 . Her abdomen was enormously enlarged and pendulous with flank fullness on both sides. An irregular mass arose from the pelvis up to the xiphisternum and was not discernible owing to abdominal wall obesity. There were no hernias or abdominal varices. Renal angle fullness was not observed. Because of the patient’s anxiety, a vaginal examination could not be performed. Transabdominal ultrasound showed a huge intraabdominal mass. The right kidney showed impaired cirrhosis, while the left kidney showed compensatory enlargement. A small amount of ascites was observed. An urgent computed tomography (CT) scan was performed revealing a large tumor that occupied the abdominopelvic cavity completely. On the CT scan, the mass measured 32 × 27 × 34 cm (intralesion diameter) and could not be visibly separated from the uterine cavity, bladder, or liver (Fig. 1 ). The tissue of origin and extent of tumor invasion remained unclear. The mass appeared heterogeneous, containing cystic and necrotic areas along with solid components. It compressed the intestines, right kidney, and both ureters. The spleen was mildly enlarged. The hepatorenal recess (Morison’s pouch) showed minimal ascites. No lymph nodes were observed. Due to the slow growth of the tumor, few ascites, and negative lymph nodes, malignancy was highly unlikely.

CT reveals extensive abdominal enlargement in the scout view ( a ). Sagittal CT reconstruction depicts a giant tumor in contact with the liver (black arrow, b ) and with the urinary bladder (black arrowhead, b ). The mass contains necrotic components (white asterisk, c ), as well as small calcifications (black asterisk, d ). The preoperative situs shows compression of the right kidney (white arrow, c ) and ascites adjacent to the tumor (white arrowhead, d )

A midline longitudinal incision was made from the xiphisternum to the pubic symphysis, and the abdomen was opened. A large mass arising from the uterus up to the xiphisternum, firm in consistency with enlarged superficial veins, was seen. The mass extended laterally to both flanks and occupied the right and left hypochondrium. No adhesions to the intestinal organs were observed. The bilateral ovaries were enlarged to twice the normal size, with ovarian artery pulsation seen on both sides. Additionally, the bilateral fallopian tube round ligaments were thickened (Fig. 2 a and b). Due to the in situ findings, a total abdominal hysterectomy en bloc with bilateral salpingectomy was performed, and both ovaries were left intraabdominally. Postoperatively, bilateral ureteric peristalsis was confirmed. Intraoperative blood loss was 400 ml. The patient’s postoperative clinical course within 5 days of hospital stay remained complication-free with quick recovery. She was discharged after 5 days of surgery and had good overall health.

The tumor shows a dilated fallopian tube and an enlarged ovary ( a ). The fibroids appear macroscopically inhomogeneous with enlarged superficial vessels ( b )

Pathology confirmed a myomatous uterus measuring 52 × 37 ×  3 cm and weighing 16.4 kg. The tumor consisted of two separate myomas with diameters of more than 30 cm. Macroscopically, the shape was irregular, with overall consistency being firm with few soft areas. The tumor was pinkish-red in color, similar to (smooth) muscle cells. On the surface, enlarged aberrant blood vessels were observed. The cervix appeared normal, as well as bilateral fallopian tubes, although they were enlarged. For further histopathological examination, a cut section (total of 38 blocks) was performed, and tissue sections were stained with hematoxylin and eosin and examined under a light microscope. The cut sections revealed a heterogeneous phenotype with predominant white whirling structures. Microscopically, the tumoral mass consisted of smooth muscle cells and collagen bundles. Few areas had nuclear polyploidy, blood vessels, and enlarged glands with some superficial hemorrhagic areas. There was no evidence of malignancy.

Although uterine leiomyomas are frequent in women, fibroids > 50 cm in size, similar to the present case, with a weight of 11.6 kg (25 lb) and more being defined as giant , are exceedingly rare. The potential for benign tumors to outgrow quietly without causing specific symptoms is reasonable because of the large volume of the abdominal cavity, flexibility, and slow growth rate of the tumor [ 2 ]. The largest myoma ever reported weighed 63.3 kg and was discovered on autopsy [ 13 ]. Online search using the PubMed database showed approximately 60 cases of giant uterine myomas in the past 50 years worldwide [ 14 ]. Table 1 summarizes the global cases of giant uterine fibroids in the past 20 years.

Preoperative imaging studies are useful to define the extent of the tumor and to assess the likelihood of malignancy in cases of expansive or infiltrative growth. Ultrasonography is the preferred technique for the initial evaluation of gynecologic pathology because of its ubiquitous availability, noninvasiveness, and convenient cost–benefit ratio [ 15 ]. In the present case, preclinical ultrasound imaging would have been absolutely appropriate with regard to diagnosis, surveillance, and prevention of myoma-associated complications. As fibroids continue to grow, they outgrow their blood supply. Therefore, giant myomas often undergo degenerative changes, and dystrophic calcification can complicate the diagnosis [ 16 ]. Although a CT scan may not be the preferred method, many myomas are detected incidentally by CT imaging [ 15 ]. The widespread clinical use of a CT scan lies in its availability, time saving, and comfortable use. Lastly, magnetic resonance imaging (MRI) is recommended to define and measure uterine pathology confidently. As our patient was claustrophobic, MRI was not suitable for her. This imaging method is predominantly utilized in first-world countries in maximum-care hospitals because of its high cost. The atypical appearance of fibroids substantially limits the preoperative informative value of all techniques [ 15 , 16 ]. Hence, the underestimation of the presented fibroid was due to its histologic composition that did not allow precise separation from the intestinal organs.

Uterine leiomyomas have been misdiagnosed as adenomyosis, hematometra, uterine sarcoma, ovarian masses, and pregnancy [ 15 , 17 , 18 ]. Other common non-gynecological differential diagnoses include gastrointestinal tumors or inflammation [ 19 ]. Fibroids often occur with endometriosis and adenomyosis, with an overlap of symptoms [ 20 ], which significantly reduces diagnostic confidence. The position of the fibroid in relation to the uterus affects the patient’s symptoms and diagnostic specificity. Myomas occur within the muscular layer (70% of all cases; intramural), on the outside (20% of all cases; subserosal), or the inside (10% of all cases; submucosal) of the uterine cavity where they possibly have a connective stalk (pedunculation). Pedunculated subserosal myomas can be acutely symptomatic owing to torsion with obstruction of blood vessels, which requires immediate surgery. They often mimic the ovarian pathology. Another differential diagnosis is uterine cancer, with carcinomas being the most frequent and sarcomas and carcinosarcomas occurring rarely [ 2 ]. Malignant transformation of a leiomyoma to a leiomyosarcoma occurs in 0.2% of all cases [ 16 ]. It should be stressed that no imaging method can rule out malignancy so far, leaving the diagnosis of a giant uterine fibroid a challenge. Fibroids of an enormous extent cannot be treated with the most widely used minimally invasive surgery techniques: hysteroscopic myomectomy, vaginal hysterectomy, or total laparoscopic hysterectomy (TLH)/laparoscopic-assisted supracervical hysterectomy (LASH). Similar to the present case, the majority of giant fibroids are removed during total abdominal hysterectomy with additional bilateral salpingo-oophorectomy, depending on the patient’s age and affection of both adnexa. Intraoperatively, severe complications such as hemodynamic instability can occur because of extensive blood loss [ 2 , 21 ]. With regard to the amount of surgery, the general morbidity and mortality in patients who receive a laparotomy is remarkably higher. Postoperative complications include venous thrombosis and acute renal failure [ 22 ]. Generally, giant myomas are fatal for the patient; therefore, such patients have to be treated similarly to older multimorbid patients [ 2 ], with death being a possible outcome [ 23 ].

The prevention of giant fibroid development with close surveillance and early surgical therapy for women with progressive myomas is the clinical gold standard. In Germany, uterine fibroids indicate surgical hysterectomy in 60.7% of all cases [ 20 ]. This underlies the fact that uterine tumors are a relevant reason for hospitalization in women. The development of such a giant myoma in the present case is surprising despite the easy accessibility to professional care and high educational standard of the population in Germany. According to Stentzel et al. , the utilization of professional care depends on several personal factors rather than travel time. In particular, a high socioeconomic status was positively correlated with visits to gynecological care [ 9 ]. Data from the cross-sectional German Health Survey (GEDA) indicate that low social status correlates with less participation in medical check-ups [ 24 ]. This strengthens the role of education in the requirement of self-consciousness and awareness of health checks.

Given the patient’s unemployment for the last 3 years and her modest family background, her low socioeconomic status could have contributed to her worsening condition. Additionally, her general anxiety and previously diagnosed depressive state of mind could have led to the rejection of professional care. The misdiagnosis by her previous doctors could be explained by her lack of complaint regarding irregular menstruation. Women with fibroids of this size are expected to most likely suffer from menstrual disorders [ 1 ], but the patient presented with menstrual irregularities only twice in the past 15 years. This possibly did not prompt her attending physicians to further evaluate the uterus as a cause of the irregular increase in abdominal size. This case was challenging to us as fibroids of this enormous size are rare, and hence, the first diagnosis of fibroid uterus was not made. Instead, it was suspected to be an ovarian carcinoma. Surgical challenges of access, intraoperative determination of anatomy, and hemorrhage were anticipated. Such large masses with uncertain diagnoses pose challenges for young and experienced surgeons alike. The patient was relieved after her treatment and was extremely thankful that she was acknowledged and not merely told that her problems were due to weight gain.

Preclinical utilization of the services of gynecologists in northern Germany depends on personal factors, such as family background, educational level, and socioeconomic status. Menstrual disorders are diverse in diagnosis and have organic and nonorganic reasons that require diagnostic clarification. Therefore, liberal utilization of physical and ultrasound examinations by general physicians could help prevent a delay in diagnosis and therapy of treatable causes such as fibroids. Giant fibroids remain a diagnostic and surgical challenge, requiring expertise and interdisciplinary cooperation. Nevertheless, these gigantic benign tumors can be managed complication-free with proper diagnosis and surgical expertise.

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Data sharing is not applicable to this article as no data were collected or analyzed>.

Abbreviations

Body mass index

Computed tomography

Magnetic resonance imaging

Total laparoscopic hysterectomy

Laparoscopic-Assisted supracervical hysterectomy

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Department of Gynecology and Obstetrics, University Medical Center UKSH, Campus Kiel, Arnold-Heller-Straße 3, Haus C, 24105, Kiel, Germany

Wiesener Viva, Dhanawat Juhi, Andresen Kristin, Alkatout Ibrahim & Bauerschlag Dirk

Spectrum Clinic and Endoscopic Research Institute, 6A and 6B Neelamber building, Shakespeare Sarani, Kolkata, West Bengal, 700020, India

Dhanawat Juhi

Institute of Pathology, University Medical Center UKSH, Campus Kiel, Arnold-Heller-Straße 3, Haus C, 24105, Kiel, Germany

Mathiak Micaela

Department of Radiology and Neuroradiology, University Medical Center UKSH, Campus Kiel, Arnold Heller Straße 3, Haus C, 24105, Kiel, Germany

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VW: manuscript writing; JD: manuscript writing; KA: data collection; MM: histology workup, provided immunohistochemical figures; MB: radiology workup, provided CT scan figures; IA: manuscript editing, surgery; DB: manuscript editing, surgery, provided figures. All authors read and approved the final manuscript.

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Viva, W., Juhi, D., Kristin, A. et al. Massive uterine fibroid: a diagnostic dilemma: a case report and review of the literature. J Med Case Reports 15 , 344 (2021). https://doi.org/10.1186/s13256-021-02959-3

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• Uterine mass
• Giant fibroid
• Misdiagnosis
• Weight gain

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The influence of uterine fibroids on adverse outcomes in pregnant women: a meta-analysis

• Hong Li 1 ,
• Zhonghua Hu 1 ,
• Yuyan Fan 1 &
• Yingying Hao 2  

BMC Pregnancy and Childbirth volume  24 , Article number:  345 ( 2024 ) Cite this article

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The objective of the meta-analysis was to determine the influence of uterine fibroids on adverse outcomes, with specific emphasis on multiple or large (≥ 5 cm in diameter) fibroids.

Materials and methods

We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed databases for eligible studies that investigated the influence of uterine fibroids on adverse outcomes in pregnancy. The pooled risk ratio (RR) of the variables was estimated with fixed effect or random effect models.

Twenty-four studies with 237 509 participants were included. The pooled results showed that fibroids elevated the risk of adverse outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, preterm premature rupture of membranes (PPROM), placental abruption, postpartum hemorrhage (PPH), fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjusting for the potential factors, negative effects were only seen for preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal death, breech presentation, and preeclampsia. Subgroup analysis showed an association between larger fibroids and significantly elevated risks of breech presentation, PPH, and placenta previa in comparison with small fibroids. Multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, and intrauterine growth restriction. Meta-regression analyses indicated that maternal age only affected the relationship between uterine fibroids and preterm birth, and BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH.

The presence of uterine fibroids poses increased risks of adverse pregnancy and obstetric outcomes. Fibroid size influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers had no impact on the risk of these outcomes.

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Introduction

Uterine fibroids are benign tumors that affect 1–10% of women of reproductive age [ 1 , 2 , 3 ]. As fibroids are usually asymptomatic, it is difficult to quantify the exact prevalence in the population. The prevalence in pregnant women, however, has been found to range from 1 to 10.7% [ 2 , 3 , 4 ] and as increasing numbers of women are delaying childbearing, these figures are likely to increase. Despite extensive investigation into ways of preventing and treating uterine fibroids, their underlying etiology is still unclear [ 5 , 6 ].

Several studies have assessed the effects of uterine fibroids on pregnancy and obstetric outcomes. However, there are many inconsistencies in their findings on the relationships between fibroids and cesarean delivery, preterm delivery, breech presentation, placenta previa, preterm premature rupture of membrane (PPROM), postpartum hemorrhage (PPH), and intrauterine growth retardation (IUGR) [ 1 , 4 , 7 , 8 , 9 , 10 , 11 ] with some investigations suggesting associations between fibroids and these complications and others reporting no elevated risks linked to the presence of fibroids [ 12 , 13 ]. The aim of this meta-analysis was to determine the influence of uterine fibroids on pregnancy and obstetric outcomes, specifically examining the effects of multiple or larger (≥ 5 cm in diameter) uterine fibroids on these adverse outcomes.

Search strategy

This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 14 ]. We searched several used electronic databases, including PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed, from their incept to January 15, 2023. The search strategy details are presented in the supplementary file 1 . The search was not restricted in terms of language or publication type. In addition, the reference lists of the included studies were manually searched to identify additional eligible articles that may have been omitted from the initial search.

Study inclusion criteria

According to the prespecified protocol, all studies that examined the associations between uterine fibroids and pregnancy/obstetric outcomes in pregnant women were included. Eligible studies were randomized controlled trials (RCTs), cohort studies, case-control studies, or comparative trials, and had to provide the pregnancy/obstetric outcomes. Reviews, letters, case reports, editorials, and comments were not included. If a clinical trial had been published in several journals, only the most informative study or the study with the longest follow-up was included to prevent duplication.

Data extraction

The extracted data included the following: (1) study information: name of first author, year of publication, country, sample size; (2) subjects’ information: sociodemographic and clinical characteristics, including maternal age, gestational age at delivery, gravidity, parity, body mass index (BMI), history of smoking, alcohol consumption, gestational diabetes mellitus, and hypertensive disorders; (3) outcome measures: cesarean delivery, fetal distress, breech presentation, intrauterine fetal death, IUGR, low birth weight, malposition, miscarriage, placenta previa, placental abruption, PPH, preeclampsia, preterm birth, and PPROM. Two independent investigators extracted the data and disagreements were addressed by discussion to reach a consensus.

Quality assessment

Two independent investigators were responsible for the assessment of methodological quality. For RCTs, methodological quality was evaluated using the Risk of Bias 2.0 tool [ 15 ] while the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) was used for interventional non-RCTs [ 16 ]. For cross-sectional studies, the Newcastle-Ottawa (NOS) scale with specific adaptations was used [ 17 ].

Statistical analysis

STATA software version 12.0 (Stata Corporation, College Station, TX, USA) was used for meta-analysis. Risk ratios (RRs) with 95% confidence intervals (95%CI) were used for dichotomous outcomes. Statistical heterogeneity among the included studies was assessed using the Cochrane Q and I 2 statistics [ 18 ], in which P  < 0.1 or I 2  > 50% were considered to be significant. In the event of significant heterogeneity, a random-effects model [ 19 ] was used for pooling the estimate or a fixed-effects model [ 20 ] was used. Sensitivity analyses were used to determine the effect of single-trial exclusions on the overall estimate. Publication bias was assessed by Begg’s [ 21 ] and Egger’s [ 22 ] tests. A P -value less than 0.05 was considered statistically significant, except where otherwise specified.

Subgroup analysis and data analysis after controlling for confounding factors

Subgroup analysis was performed to analyze the effects of uterine fibroid size (small [< 5 cm in diameter] vs. large [≥ 5 cm in diameter]) and number (single fibroids VS multiple fibroids). The size of leiomyomas was quantified by measuring the largest diameter. Consistent with previous research, we classified a fibroid as large when its diameter reached or exceeded 5 cm, as determined through ultrasonography [ 23 ].

Several of the included studies used univariate and multivariate logistic regression to assess relationships between uterine fibroids and pregnancy/obstetric outcomes. In these studies, the authors provided the adjusted odds ratio (OR) or RR after controlling for potential confounders, such as maternal age, race, BMI, parity, diabetes, hypertension, alcohol, and smoking. Thus, we extracted the adjusted values for data analysis.

Meta-regression analysis

We hypothesized that various factors might have affected the results of the included studies; these included demographic (maternal age and BMI) and clinical (gravidity, parity, smoking status, diabetes mellitus, and hypertension) variables. We, therefore, conducted a meta-regression analysis to determine the possible effects of these variables on the reported results. In the regression model, the outcome was regarded as the dependent variable (y) and the covariates described above as the independent variables (χ).

Study identification

A total of 2512 potentially relevant articles were identified from the database searches together with six additional articles from other sources. Of these, 1542 were duplicates and were removed, leaving 976 articles for article/abstract review. Of these, 935 were excluded because of various reasons. The full texts of the 41 remaining articles were reviewed, resulting in the exclusion of 17 articles. Finally, 24 studies [ 1 , 4 , 7 , 12 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] were considered to meet the inclusion criteria and were included for qualitative synthesis (Fig.  1 ).

Eligibility of studies for inclusion in meta-analysis

Characteristics of included studies and quality assessment

The baseline features of the included studies are shown in supplementary file 2 . All the studies had a retrospective cohort design, with seventeen carried out in China [ 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], five in the USA [ 1 , 4 , 7 , 27 ], one in Italy [ 25 ], and one in France [ 24 ]. Sample sizes ranged from 127 to 112 403 participants. These studies included a total of 237 509 participants, of whom 10 560 were cases (women with uterine fibroids) and 226 949 were controls (women without uterine fibroids). As a consequence of family planning and the one-child policy, women from China tended to be primigravidae. In some of the included studies, women with uterine fibroids tended to be older, smokers, and drinkers, and to have higher BMI, or histories of diabetes mellitus and chronic hypertension, compared with those without fibroids.

Overall, the risk of bias in the cohort studies ranged from serious to low. Low bias risk was associated with intervention classification and analysis, deviations from intended interventions, and missing data. The risk of bias in confounding was deemed serious in four studies, with no information in three studies, critical in two studies, and low in the other studies. Bias risk in participant selection was found to be moderate in three studies, with no information in one study, and low in the other studies. Bias risk outcome measurement was moderate in one study and low in other studies while the risk in the selection of result reporting was deemed serious in two studies, moderate in three studies, and low in other studies. Overall, the risk of bias was critical in two studies [ 36 , 37 ], serious in six studies [ 35 , 38 , 39 , 41 , 42 , 43 ], moderate in five studies [ 27 , 28 , 30 , 31 , 33 ], and low in eleven studies [ 1 , 4 , 7 , 12 , 24 , 25 , 26 , 29 , 32 , 34 , 40 ] (Supplementary file 3 ).

Preterm birth

Twenty-one studies [ 1 , 4 , 7 , 12 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] reported data on preterm birth. The preterm birth rate for pregnant women with uterine fibroids was 12.85% compared with 9.43% for the no-fibroid group. Pooled data showed that the presence of uterine fibroids posed a higher risk for preterm birth (RR = 1.72, 95%CI: 1.41, 2.10; P  < 0.001). Significant heterogeneity was observed in the included studies (I 2  = 74.5%, P  < 0.001). Sensitivity analysis was conducted by the exclusion of an outlier trial [ 29 ] resulting in a slight alteration in the overall estimate (RR = 1.82, 95%CI: 1.49, 2.22; P  < 0.001) with the heterogeneity still present (I 2  = 73.6%, P  < 0.001). Sensitivity analysis using the exclusion of a trial with a small sample size [ 39 ] also resulted in a small alteration in the pooled data (RR = 1.69, 95%CI: 1.39, 2.05; P  < 0.001), with the heterogeneity remaining (I 2  = 74.8%, P  < 0.001). Further successive exclusion of the remaining single studies did not change the overall estimates and heterogeneity (data not shown).

Cesarean delivery

Eighteen studies [ 1 , 4 , 7 , 24 , 25 , 26 , 29 , 30 , 31 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 ] reported data on cesarean delivery. The cesarean delivery rate in the fibroid group was 60.72% compared with 39.03% for the no-fibroid group. The aggregated data showed that fibroid presence led to an elevated risk of cesarean delivery (RR = 1.95, 95%CI: 1.67, 2.28; P  < 0.001). The test for heterogeneity was significant (I 2  = 96.8%, P  < 0.001). The exclusion of an outlying trial [ 40 ] resulted in a slight change in the overall estimate slightly (RR = 1.86, 95%CI: 1.59, 2.17; P  < 0.001) while heterogeneity was still present (I 2  = 96.7%, P  < 0.001). The exclusion of a trial with a small sample size [ 39 ] produced a similar effect, with no alteration in the overall estimate (RR = 1.92, 95%CI: 1.64, 2.25; P  < 0.001) and the continued presence of heterogeneity (I 2  = 96.9%, P  < 0.001).

Placenta previa

Sixteen studies [ 1 , 4 , 7 , 24 , 25 , 26 , 28 , 29 , 31 , 32 , 34 , 38 , 39 , 40 , 41 , 42 ] reported data on placenta previa. The placenta previa rate for pregnant women with uterine fibroids was 2.48% compared with 0.98% for the no-fibroid group. The aggregated data showed that the presence of uterine fibroids significantly raised the risk of placenta previa (RR = 2.99, 95%CI: 2.06, 4.35; P  < 0.001). There was significant heterogeneity (I 2  = 65.6%, P  < 0.001). The exclusion of an outlying trial [ 32 ] did not alter the overall estimate (RR = 2.86, 95%CI: 1.97, 4.15; P  < 0.001) or the heterogeneity (I 2  = 65.7%, P  < 0.001). Similarly, the exclusion of a trial with a small sample size [ 39 ] did not affect the overall estimate (RR = 2.92, 95%CI: 1.99, 4.30; P  < 0.001) or the heterogeneity (I 2  = 67.1%, P  < 0.001).

Miscarriage

Fifteen studies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 41 , 42 , 43 ] reported data on miscarriage. The miscarriage rate for pregnant women with uterine fibroids was 13.42% compared with 2.84% for the no-fibroid group. The pooled data indicated a significantly elevated risk of miscarriage associated with the presence of fibroids (RR = 4.51, 95%CI: 2.80, 7.26; P  < 0.001). Significant heterogeneity was observed (I 2  = 51.3%, P  = 0.011). The exclusion of an outlying trial [ 38 ] did not alter the overall estimate (RR = 4.28, 95%CI: 2.64, 6.94; P  < 0.001) or heterogeneity (I 2  = 51.8%, P  = 0.012) significantly, while the exclusion of the trial with a small sample size [ 39 ] also did not affect the overall estimate (RR = 4.47, 95%CI: 2.70, 7.40; P  < 0.001) or the heterogeneity (I 2  = 54.3%, P  = 0.008).

Preterm premature rupture of membranes

Fifteen studies [ 1 , 4 , 7 , 12 , 24 , 25 , 26 , 27 , 29 , 35 , 36 , 37 , 40 , 42 , 43 ] reported data on PPROM. The PPROM rates in the fibroid and no-fibroid groups were 9.65% and 9.53%, respectively. As shown by the pooled estimate, fibroid presence was associated with a significantly higher risk of PPROM in comparison with no fibroids (RR = 1.37, 95%CI: 1.09, 1.72; P  < 0.001). Significant heterogeneity was observed (I 2  = 74.7%, P  < 0.001). However, sensitivity analysis involving the exclusion of single studies did not identify the source of the heterogeneity.

Placental abruption

Fourteen studies [ 4 , 12 , 24 , 27 , 30 , 35 , 36 , 37 , 39 , 43 ] reported data om placental abruption. The rate of placental abruption for pregnant women with uterine fibroids was 6.28% compared with 5.51% for the no-fibroid group. The pooled data indicated that fibroids significantly raised the risk of placental abruption (RR = 1.85, 95%CI: 1.48, 2.32; P  < 0.001). No significant heterogeneity among the studies was observed (I 2  = 36.3%, P  = 0.086).

Postpartum hemorrhage

Thirteen studies [ 26 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 38 , 40 , 41 , 42 ] reported data on PPH. The rate of PPH for pregnant women with uterine fibroids was 10.10% compared with 3.96% for the no-fibroid group. As shown by the pooled data, the presence of fibroids raised the risk of PPH significantly (RR = 3.52, 95%CI: 2.16, 5.73; P  < 0.001). Significant heterogeneity was observed among the studies (I 2  = 80.8%, P  < 0.001) while sensitivity analysis was unable to identify the source of the heterogeneity.

Fetal distress

Sixteen studies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] reported data on fetal distress. The rates of fetal distress were 11.47% and 4.68% for the fibroid and no-fibroid groups, respectively and the pooled data indicated that the risk was significantly increased by the presence of fibroids (RR = 3.61, 95%CI: 2.08, 6.27; P  < 0.001). Significant heterogeneity was observed (I 2  = 72.8%, P  < 0.001) while the source of the heterogeneity was not identified by sensitivity analysis.

Malposition

Sixteen studies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] reported data on malposition. The malposition rate for the fibroid group was 14.41% compared with 14.38% for the no-fibroid group with the pooled data showing a significant risk for malposition in the fibroid group (RR = 2.54, 95%CI: 1.75, 3.69; P  < 0.001). Significant heterogeneity was observed (I 2  = 64.7%, P  < 0.001) which remained unaffected by sensitivity analysis.

Intrauterine fetal death

Ten studies [ 1 , 12 , 29 , 30 , 33 , 34 , 35 , 36 , 37 , 43 ] reported data on intrauterine fetal death. The rate of intrauterine fetal death in the fibroid group was 3.07% compared with 0.69% for the no-fibroid group, with pooled data showing a significant risk for intrauterine fetal death resulting from the presence of fibroids (RR = 2.34, 95%CI: 1.42, 3.84; P  < 0.001). Significant heterogeneity was seen (I 2  = 50.5%, P  = 0.0033). Exclusion of an outlying trial [ 34 ] altered the overall estimate slightly (RR = 2.57, 95%CI: 1.95, 3.39; P  < 0.001) and also eliminated the heterogeneity (I 2  = 0.0%, P  = 0.706), indicating that the trial of Xu JZ [ 34 ] was responsible for the heterogeneity among the included studies.

Low birth weight

Eight studies [ 12 , 29 , 31 , 32 , 34 , 39 , 40 , 42 ] reported data on low birth weight. The rates for the fibroid and no-fibroid groups were 11.53% and 10.40%, respectively, with the pooled data showing a significant increase in the risk of low birth rate in the fibroid group (RR = 1.72, 95%CI: 1.03, 2.85; P  < 0.001). Although significant heterogeneity was observed (I 2  = 73.0%, P  = 0.001), this remained unaffected by sensitivity analysis.

Breech presentation

Six studies [ 1 , 4 , 7 , 25 , 26 , 34 ] reported data on breech presentation. The rate of breech presentation for pregnant women with uterine fibroids was 8.30% compared with 3.70% for the no-fibroid group. Pooled data showed that the presence of uterine fibroids significantly elevated the risk of breech presentation (RR = 2.26, 95%CI: 1.56, 3.29; P  < 0.001). Significant heterogeneity among the studies was observed (I 2  = 91.2%, P  < 0.001) but its source was not identified by sensitivity analysis.

Intrauterine growth retardation

Six studies [ 1 , 25 , 29 , 31 , 32 , 34 ] reported data on IUGR. The rate of IUGR was 10.69% in the fibroid group compared with 12.97% in the no-fibroid group. The pooled data did not show any increased risk of IUGR associated with fibroids (RR = 1.25, 95%CI: 0.61, 2.55; P  = 0.543). No significant heterogeneity was observed (I 2  = 47.7%, P  = 0.088).

Preeclampsia

Five studies [ 1 , 4 , 24 , 29 , 42 ] reported data on preeclampsia. The preeclampsia rates were 5.93% and 5.94% for the fibroid and no-fibroid groups, respectively, with pooled data indicating a significantly elevated risk in the fibroid group (RR = 1.48, 95%CI: 1.10, 2.00; P  = 0.009). Significant heterogeneity among the studies was observed (I 2  = 52.3%, P  = 0.079).

Data analysis after adjusting for potential confounder factors

Nine studies [ 1 , 4 , 7 , 12 , 24 , 26 , 30 , 33 , 42 ] provided the adjusted values for controlling the potential confounder factors. The pooled data indicated that the presence of fibroids significantly elevated the risks of breech presentation (RR = 1.88, 95%CI: 1.18, 2.99; P  = 0.008), placental abruption (RR = 1.94, 95%CI: 1.19, 3.16; P  = 0.008), PPH (RR = 2.29, 95%CI: 1.78, 2.94; P  < 0.001), preeclampsia (RR = 1.20, 95%CI: 1.02, 1.42; P  = 0.031), intrauterine fetal death (RR = 1.82, 95%CI: 1.01, 3.28; P  = 0.046), preterm birth (RR = 1.48, 95%CI: 1.12, 1.96; P  = 0.006), cesarean delivery (RR = 2.13, 95%CI: 1.12, 4.04; P  = 0.021), and placenta previa (RR = 1.62, 95%CI: 1.03, 2.53; P  = 0.037). No significant associations were seen between fibroid presence and PPROM (RR = 1.30, 95%CI: 0.98, 1.72; P  = 0.073) and low birth weight (RR = 1.36, 95%CI: 0.87, 2.13; P  = 0.172) (Table  1 ).

Subgroup analysis of uterine fibroid size and number

Five studies [ 1 , 7 , 25 , 26 , 27 ] reported data that evaluated the effects of fibroid size and number on outcomes. The subgroup analysis analyzing fibroid size showed that the presence of large fibroids significantly elevated the risk of breech presentation (RR = 1.50, 95%CI: 1.03, 2.19; P  = 0.036), placenta previa (RR = 5.04, 95%CI: 2.12, 12.01; P  < 0.001), and PPH (RR = 1.62, 95%CI: 1.16, 2.25; P  = 0.004), compared with small fibroids. Small fibroids, however, significantly raised the risk of breech presentation (RR = 1.40, 95%CI: 1.10, 1.79; P  = 0.006), placental abruption (RR = 3.75, 95%CI: 2.83, 4.97; P  < 0.001), cesarean delivery (RR = 1.48, 95%CI: 1.33, 1.65; P  < 0.001), PPH (RR = 1.65, 95%CI: 1.41, 1.92; P  < 0.001), and IUGR (RR = 1.15, 95%CI: 1.01, 1.30; P  = 0.029), compared with an absence of fibroids (Table  2 ).

Subgroup analysis of the effects of fibroid number showed that the presence of multiple fibroids did not increase the risk of PPROM (RR = 1.31, 95%CI: 0.55, 3.13; P  = 0.545), placental abruption (RR = 1.22, 95%CI: 0.51, 2.94; P  = 0.651), placenta previa (RR = 1.50, 95%CI: 0.90, 2.51; P  = 0.122), preterm birth (RR = 0.87, 95%CI: 0.51, 1.50; P  = 0.627), cesarean delivery (RR = 0.85, 95%CI: 0.50, 1.44; P  = 0.539), and PPH (RR = 1.45, 95%CI: 0.53, 3.95; P  = 0.464), compared with a single fibroid (Table  2 ).

To further evaluate the influence of potential confounding factors (maternal age, BMI, parity, gravidity, smoking status, diabetes mellitus, and hypertension) on the outcomes, we conducted meta-regression analyses. While maternal age affected the difference in preterm birth between the fibroid and no-fibroid groups (t = 2.87, P  = 0.012), other factors did not (Table  3 ). BMI influenced the difference in intrauterine fetal death (t = 3.13, P  = 0.04) while other factors did not. None of these factors influenced malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH (Table  3 ).

Publication bias

The determination of potential publication bias using Egger’s and Begg’s tests indicated an absence of publication bias in the included studies (Egger’s test: t = 0.68, P  = 0.533; Begg’s test: Z = 1.13, P  = 0.260).

This meta-analysis was performed to investigate the impact of uterine fibroids on adverse pregnancy outcomes, specifically evaluating the effects of multiple or large (≥ 5 cm in diameter) uterine fibroids on the adverse outcomes. Our findings indicated that fibroids elevated the risk of certain pregnancy and obstetric outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, PPROM, placental abruption, PPH, fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjustment, these negative effects were confined to preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal demise, breech presentation, and preeclampsia.

Moreover, results from subgroup analysis showed a relationship between the presence of larger fibroids and significantly higher risks of breech presentation, PPH, and placenta previa compared with small fibroids. The presence of multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, or IUGR.

In the meta-regression analysis, we also found that only maternal age affected the relationship between uterine fibroids and preterm birth, while BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH.

The biological basis for the associations between fibroids and adverse outcomes is not clear. Several studies, however, have suggested that reduced uterine distension resulting from physical interference by the fibroids may be one of the reasons [ 44 ]. Moreover, women with fibroids have been found to have lower oxytocinase activity, leading to higher levels of oxytocin which, in turn, would lead to preterm contractions [ 45 ]. It is also possible that degraded submucosal fibroids may lead to chronic inflammation or infection, with the consequent production of cytokines potentially resulting in elevated risks for preterm delivery [ 13 ].

In this study, we screened the recent literature with the objective of evaluating the influence of uterine fibroids on adverse outcomes. Twenty-four studies were finally included in the analysis. All these studies used a retrospective cohort design and the ROBINS-1 method was, therefore, used to evaluate their quality. Eleven of the studies were considered to have a low risk of bias, with five showing moderate risk, six serious risk, and two showing a critical bias risk. Bias in cofounding factors and the selection of reported results can result in a low quality of evidence. Our research highlighted that several adverse outcomes were strongly associated with the presence of uterine fibroids. However, when we pooled data from studies that provided the adjusted RR estimate for confounding factors, we found that the risks of PPROM and low birth weight were not significantly raised by the presence of fibroids.

In the meta-regression, we noticed that maternal age was positively related to preterm birth (Coefficient = 21.05, P  = 0.01). This finding agrees with previous evidence that the preterm birth risk increased with increasing maternal age [ 46 , 47 , 48 ]. Leader J, et al. [ 46 ] in a meta-analysis of 15 studies found that women with very advanced maternal ages (≥ 45 years old) had a 1.96-times greater likelihood of preterm birth. Similarly, in another meta-analysis [ 47 ] including 10 studies, the authors found that women of advanced maternal age (≥ 35 years old) were more likely to have preterm deliveries than younger women [35–40 years old (OR = 1.21, 95%CI: 1.16, 1.27) and those > 40 years old (OR = 1.18, 95%CI: 1.10, 1.27)]. Besides maternal age, the meta-regression found that BMI was significantly related to intrauterine fetal death. Aune D, et al. [ 49 ] in a systematic review and meta-analysis comprising 38 cohort studies investigating whether specific levels of BMI increased the likelihood of fetal or infant death found that the pooled RR per five-unit increase in BMI for fetal death was 1.21 (95%CI: 1.09, 1.35) and was 1.24 (95%CI: 1.18, 1.30) for stillbirth.

In this meta-analysis, we not only investigated the effects of uterine fibroids on major outcomes, such as preterm birth, cesarean delivery, breech presentation, malposition, fetal distress, PPROM, miscarriage, IUGR, placenta previa, and placental abruption but have also analyzed the outcomes in terms of fibroid size and number. Although several studies have investigated these aspects, the results were inconsistent due to small sample sizes. Here, we found that women with fibroids greater than 5 cm in diameter had an increased risk of breech presentation, PPH, or placenta previa, compared with women with fibroids less than 5 cm. However, in terms of fibroid numbers, we observed that the presence of multiple fibroids did not increase the risk of placental abruption, cesarean delivery, PPH, placenta previa, PPROM, and preterm birth, compared with single fibroids. These results suggested that only the size of the fibroids influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers did not affect these outcomes. There are very few studies on the associations between fibroid size and number on adverse outcomes. Our results provide valuable information for the identification of the risks of breech presentation, PPH, and placenta previa.

This meta-analysis has several potential limitations. First, the meta-analysis pooled data from 24 studies with 237 509 participants; while this increased the statistical power for determining the influence of uterine fibroids on adverse outcomes, it also led to heterogeneity. Some heterogeneity might be explained by differences in geographical locations and participants’ characteristics. We conducted sensitivity analyses to identify the potential sources of this heterogeneity; unfortunately, this was unable to identify the sources. Second, several of the included studies did not adjust for potential confounding factors, and the factors selected for adjustment differed across the studies. This might have influenced the overall estimate. Third, the meta-analysis was based on retrospective cohort studies. Such studies are subject to selection bias as they rely on care utilization and imaging data and recruit subjects only from academic medical centers. Fourth, most of the included studies were conducted in China, which may prevent the broad generalizability of our results. Finally, it is important to note that due to the limitations of the available data, we were unable to conduct subgroup analyses based on fibroid size, specifically for those with a diameter exceeding 10 cm, and fibroid location. This limitation restricted our ability to fully explore the impact of these variables on the outcomes.

Despite these weaknesses, our meta-analysis has some notable strengths. First, the large sample size of 237 509 participants from 24 included studies resulted in increased statistical power and, consequently, more reliable and accurate findings. Second, our study provided more comprehensive information compared with previous meta-analyses. Other meta-analyses have only focused on one pregnancy or obstetric outcomes, such as placenta abruption, placenta previa, or preterm birth [ 50 , 51 , 52 ]. Third, to minimize the effect of confounding factors on our results, we corrected our analyses for multiple confounders using meta-regression analysis and pooled data. Fourth, we developed a complete and comprehensive search strategy, as well as accessing articles from multiple databases and the gray literature, to minimize missing potential studies. We also used stringent screening criteria in the literature selection and strict statistical methods in the data analysis to improve the accuracy of our results. Last, we included recently published studies, which ensures that our results are more applicable to present clinical settings.

In conclusion, this meta-analysis suggested that women with uterine fibroids have elevated risks of pregnancy and obstetric outcomes. Specifically, fibroid size was found to influence the risk of breech presentation, PPH, and placenta previa, while the number of fibroids did not affect the risk of these outcomes.

Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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This study was funded by Liaoning Provincial Natural Science Foundation of China (No. 2023-MS-155), and Liaoning Provincial Public Welfare Research Fund for Science (Soft Science Research Program) (No. 2023JH4/10600030).

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Li, H., Hu, Z., Fan, Y. et al. The influence of uterine fibroids on adverse outcomes in pregnant women: a meta-analysis. BMC Pregnancy Childbirth 24 , 345 (2024). https://doi.org/10.1186/s12884-024-06545-5

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MARIA SYL D. DE LA CRUZ, MD, AND EDWARD M. BUCHANAN, MD

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Uterine fibroids are common benign neoplasms, with a higher prevalence in older women and in those of African descent. Many are discovered incidentally on clinical examination or imaging in asymptomatic women. Fibroids can cause abnormal uterine bleeding, pelvic pressure, bowel dysfunction, urinary frequency and urgency, urinary retention, low back pain, constipation, and dyspareunia. Ultrasonography is the preferred initial imaging modality. Expectant management is recommended for asymptomatic patients because most fibroids decrease in size during menopause. Management should be tailored to the size and location of fibroids; the patient's age, symptoms, desire to maintain fertility, and access to treatment; and the experience of the physician. Medical therapy to reduce heavy menstrual bleeding includes hormonal contraceptives, tranexamic acid, and nonsteroidal anti-inflammatory drugs. Gonadotropin-releasing hormone agonists or selective progesterone receptor modulators are an option for patients who need symptom relief preoperatively or who are approaching menopause. Surgical treatment includes hysterectomy, myomectomy, uterine artery embolization, and magnetic resonance–guided focused ultrasound surgery.

Uterine fibroids, or leiomyomas, are the most common benign tumors in women of reproductive age. 1 Their prevalence is age dependent; they can be detected in up to 80% of women by 50 years of age. 2 Fibroids are the leading indication for hysterectomy, accounting for 39% of all hysterectomies performed annually in the United States. 3 Although many are detected incidentally on imaging in asymptomatic women, 20% to 50% of women are symptomatic and may wish to pursue treatment. 4

WHAT IS NEW ON THIS TOPIC: UTERINE FIBROIDS

Compared with total laparoscopic hysterectomy or laparoscopically assisted vaginal hysterectomy, vaginal hysterectomy is associated with shorter operative time, less blood loss, shorter paralytic ileus time, and shorter hospitalization.

In 2014, the U.S. Food and Drug Administration recommended limiting the use of laparoscopic power morcellation to reproductive-aged women who are not candidates for en bloc uterine resection. Morcellation should not be used in women with suspected or known uterine cancer.

An estimated 15% to 33% of fibroids recur after myomectomy, and approximately 10% of women undergoing myomectomy will undergo a hysterectomy within five to 10 years.

Epidemiology and Etiology

Fibroids are benign tumors that originate from the uterine smooth muscle tissue (myometrium) whose growth is dependent on estrogen and progesterone. 5 , 6 Fibroids are rare before puberty, increase in prevalence during the reproductive years, and decrease in size after menopause. 6 Aromatase in fibroid tissue allows for endogenous production of estradiol, and fibroid stem cells express estrogen and progesterone receptors that facilitate tumor growth in the presence of these hormones. 5 Protective factors and risk factors for fibroid development are listed in Table 1 . 7 – 9 The major risk factors for fibroid development are increasing age (until menopause) and African descent. 7 , 8 Compared with white women, black women have a higher lifetime prevalence of fibroids and more severe symptoms, which can affect their quality of life. 10

Clinical Features

Uterine fibroids are classified based on location: subserosal (projecting outside the uterus), intramural (within the myometrium), and submucosal (projecting into the uterine cavity). The symptoms and treatment options are affected by the size, number, and location of the tumors. 11 The most common symptom is abnormal uterine bleeding, usually excessive menstrual bleeding. 12 Other symptoms include pelvic pressure, bowel dysfunction, urinary frequency and urgency, urinary retention, low back pain, constipation, and dyspareunia. 13

Uterine fibroids may be associated with infertility, and some experts recommend that women with infertility be evaluated for fibroids, with potential removal if the tumors have a submucosal component. 14 However, there is no evidence from randomized controlled trials to support myomectomy to improve fertility. 15 One meta-analysis included two studies that showed improvement in spontaneous conception rates in women who underwent myomectomy for submucosal fibroids (relative risk [RR] = 2.034; 95% confidence interval [CI], 1.081 to 3.826; P = .028). 16 However, no statistically significant difference was noted in the ongoing pregnancy/live birth rate. Women with intramural fibroids had no differences in pregnancy rates after undergoing myomectomy. Although studies have had conflicting results on the change in fibroid size during pregnancy, 17 , 18 a large retrospective study of women with uterine fibroids found a significantly increased risk of cesarean delivery compared with a control group (33.1% vs. 24.2%), as well as increases in the risk of breech presentation (5.3% vs. 3.1%), pre-term premature rupture of membranes (3.3% vs. 2.4%), delivery before 37 weeks' gestation (15.1% vs. 10.5%), and intrauterine fetal death with growth restriction (3.9% vs. 1.5%). 19 Therefore, fibroids in pregnant women warrant additional maternal and fetal surveillance.

In the postpartum period, women with fibroids have an increased risk of postpartum hemorrhage secondary to an increased risk of uterine atony. 20 The risk of malignancy for uterine fibroids is very low; the prevalence of leiomyosarcoma is estimated at about one in 400 (0.25%) women undergoing surgery for fibroids. 21 Because the natural course of fibroids involves growth and regression, enlarging fibroids are not an indication for removal. 22 , 23

The evaluation of fibroids is based mainly on the patient's presenting symptoms: abnormal menstrual bleeding, bulk symptoms, pelvic pain, or findings suggestive of anemia. Fibroids are sometimes found in asymptomatic women during routine pelvic examination or incidentally during imaging. 24 In the United States, ultrasonography is the preferred initial imaging modality for fibroids. 4 Transvaginal ultrasonography is about 90% to 99% sensitive for detecting uterine fibroids, but it may miss subserosal or small fibroids. 25 , 26 Adding sonohysterography or hysteroscopy improves sensitivity for detecting submucosal myomas. 25 There are no reliable means to differentiate benign from malignant tumors without pathologic evaluation. Some predictors of malignancy on magnetic resonance imaging include age older than 45 years (odds ratio [OR] = 20), intratumoral hemorrhage (OR = 21), endometrial thickening (OR = 11), T2-weighted signal heterogeneity (OR = 10), menopausal status (OR = 9.7), and nonmyometrial origin (OR = 4.9). 27 , 28 Risk factors for leiomyosarcoma include radiation of the pelvis, increasing age, and use of tamoxifen, 29 , 30 which has implications for surgical management of fibroids. Table 2 includes the differential diagnosis of uterine masses. 31

Treatment of uterine fibroids should be tailored to the size and location of the tumors; the patient's age, symptoms, desire to maintain fertility, and access to treatment; and the physician's experience 4 , 11 ( Table 3 32 – 42 and Table 4 4 , 16 , 34 , 38 , 40 – 44 ) . The ideal treatment satisfies four goals: relief of signs and symptoms, sustained reduction of the size of fibroids, maintenance of fertility (if desired), and avoidance of harm. Figure 1 presents an algorithm for the management of uterine fibroids. 4

EXPECTANT THERAPY

About 3% to 7% of untreated fibroids in premenopausal women regress over six months to three years, and most decrease in size at menopause. Because there is minimal concern for malignancy in women with asymptomatic fibroids, watchful waiting is preferred - for management. 4 There are no studies that support - surveillance with imaging or repeat imaging in asymptomatic women with fibroids. 4 , 11

MEDICAL THERAPY

Hormonal Contraceptives . Women who use combined oral contraceptives have significantly less self-reported menstrual blood loss after 12 months compared with placebo. 33 However, the levonorgestrel-releasing intra-uterine system (Mirena) results in a significantly greater reduction in menstrual blood loss at 12 months vs. oral contraceptives (mean reduction = 91% vs. 13% per cycle; P < .001). 33 In six prospective observational studies, reported expulsion rates of intrauterine devices were between zero and 20% in women with uterine fibroids. 45 There is a lack of high-quality evidence regarding oral and injectable progestin for uterine fibroids. 46 – 48

Tranexamic Acid . Tranexamic acid (Cyklokapron) is an oral nonhormonal antifibrinolytic agent that significantly reduces menstrual blood loss compared with placebo (mean reduction = 94 mL per cycle; 95% CI, 36 to 151 mL). 37 , 38 One small nonrandomized study reported a higher rate of fibroid necrosis in patients who received tranexamic acid compared with untreated patients (15% vs. 4.7%; OR = 3.60; 95% CI, 1.83 to 6.07; P = .0003), with intralesional thrombi in one-half of the 22 cases involving fibroid necrosis (manifesting as apop-totic cellular debris with inflammatory cells, and usually hemorrhage). 49 However, in a systematic review of four studies with 200 patients who received tranexamic acid, none of the studies detailed the adverse effects of fibroid necrosis or thrombus formation. 50

Nonsteroidal Anti-inflammatory Drugs . Another medical option for the treatment of uterine fibroids is a non-steroidal anti-inflammatory drug. These agents significantly reduce blood loss (mean reduction = 124 mL per cycle; 95% CI, 62 to 186 mL) and improve pain relief compared with placebo, 34 but are less effective in decreasing blood loss compared with the levonorgestrel-releasing intrauterine system or tranexamic acid at three months. 51

Hormone Therapy . Gonadotropin-releasing hormone (GnRH) agonists and selective progesterone receptor modulators (SPRMs) are options for patients who need temporary relief from symptoms preoperatively or who are approaching menopause. Preoperative administration of GnRH agonists (e.g., leuprolide [Lupron], goserelin [Zoladex], triptorelin [Trelstar Depot]) increases hemoglobin levels preoperatively by 1.0 g per dL (10 g per L) and postoperatively by 0.8 g per dL (8 g per L), as well as significantly decreases pelvic symptom scores. 32 Adverse effects resulting from the hypoestrogenized state, including hot flashes (OR = 6.5), vaginitis (OR = 4.0), sweating (OR = 8.3), and change in breast size (OR = 7.7), affect the long-term use of these agents. 32

Compared with placebo, the SPRM mife-pristone (Mifeprex) significantly decreases heavy menstrual bleeding (OR = 18; 95% CI, 6.7 to 47) and improves fibroid-specific quality of life, but does not affect fibroid volume. 35 Ulipristal (Ella) is an SPRM approved as a contraceptive in the United States but used in other countries for the treatment of fibroids in adult women who are eligible for surgery. Compared with placebo, a 5-mg dose of ulipristal significantly reduces mean blood loss (94% vs. 48% per cycle; 95% CI, 55% to 83%; P < .001), decreases fibroid volume by more than 25% (85% vs. 45%; 95% CI, 4% to 39%; P = .01), and induces amenorrhea in significantly more patients (94% vs. 48%; 95% CI, 50% to 77%; P < .001). 52 Treatment is limited to three months of continuous use. The most common adverse effects include headache and breast tenderness. The advantage of SPRMs over GnRH agonists for preoperative adjuvant therapy is their lack of hypoestrogenic adverse effects and bone loss. However, SPRMs can result in progesterone receptor modulator–associated endometrial changes, although these seem to be benign. 36

Other Agents . Other, less-studied options for the treatment of uterine fibroids include aromatase inhibitors and estrogen receptor antagonists. Aromatase inhibitors (e.g., letrozole [Femara], anastrozole [Arimidex], fadrozole [not available in the United States]) block the synthesis of estrogen. Limited data have shown that they help reduce fibroid size as well as decrease menstrual bleeding, with adverse effects including hot flashes, vaginal dryness, and musculoskeletal pain. 53 , 54 Overall, there is insufficient evidence to support the use of aromatase inhibitors for the treatment of uterine fibroids. 55 Selective estrogen receptor modulators act as partial estrogen receptor agonists in bone, cardiovascular tissue, and the endometrium. In a small prospective trial of 18 patients, tamoxifen did not reduce fibroid size or uterine volume, but did reduce menstrual blood loss by 40% to 50% and decrease pelvic pain compared with the control group. 56 Based on its adverse effects (e.g., hot flashes, dizziness, endometrial thickening), the authors concluded that its risks outweigh its marginal benefits for fibroid treatment. Another selective estrogen receptor modulator, raloxifene (Evista), has also shown inconsistent results, with two of three studies included in a Cochrane review showing significant benefit. 57

Hysterectomy . Hysterectomy provides a definitive cure for women with symptomatic fibroids who do not wish to preserve fertility, resulting in complete resolution of symptoms and improved quality of life. Hysterectomy by the least invasive approach possible is the most effective treatment for symptomatic uterine fibroids. 39 Vaginal hysterectomy is the preferred technique because it provides several statistically significant advantages, including shorter surgery time than total laparoscopic hysterectomy or laparoscopically assisted vaginal hysterectomy (70 minutes vs. 151 minutes vs. 130 minutes, respectively), decreased blood loss (183 mL vs. 204 mL vs. 358 mL), shorter hospitalization (51 hours vs. 77 hours vs. 77 hours), and shorter paralytic ileus time (19 hours vs. 28 hours vs. 26 hours); however, vaginal hysterectomy is limited by the size of the myomatous uterus. 43 Abdominal hysterectomy is an alternative approach, but the balance of risks and benefits must be individualized to each patient. 44

The laparoscopic extraction of the uterus may be performed with morcellation, whereby a rotating blade cuts the tissue into small pieces. This technique has come under scrutiny because of concerns about iatrogenic dissemination of benign and malignant tissue. The U.S. Food and Drug Administration recommends limiting the use of laparoscopic morcellation to reproductive-aged women who are not candidates for en bloc uterine resection. 58 The American College of Obstetricians and Gynecologists recommends morcellation as an option, but emphasizes the importance of informed consent and notes that the technique should not be performed in women with suspected or known uterine cancer. 59 , 60 Approximately one in 10 women have new symptoms after hysterectomy with bilateral salpingo-oophorectomy. 61

Myomectomy . Hysteroscopic myomectomy is the preferred surgical procedure for women with submucosal fibroids who wish to preserve their uterus or fertility. It is optimal for submucosal fibroids less than 3 cm when more than 50% of the tumor is intracavitary. 62 Laparoscopy is associated with less postoperative pain at 48 hours, less risk of postoperative fever (OR = 0.44; 95% CI, 0.26 to 0.77), and shorter hospitalization (mean of 67 fewer hours; 95% CI, 55 to 79 hours) compared with open myomectomy. 41 An estimated 15% to 33% of fibroids recur after myomectomy, and approximately 10% of women who undergo this procedure will have a hysterectomy within five to 10 years. 24

Uterine Artery Embolization . Uterine artery embolization is an option for women who wish to preserve their uterus or avoid surgery because of medical comorbidities or personal preference. 4 It is an interventional radiologic procedure in which occluding agents are injected into one or both of the uterine arteries, limiting blood supply to the uterus and fibroids. Compared with hysterectomy and myomectomy, uterine artery embolization has a significantly decreased length of hospitalization (mean of three fewer days), decreased time to normal activities (mean of 14 days), and a decreased likelihood of blood transfusion (OR = 0.07; 95% CI, 0.01 to 0.52). 42 Long-term studies show a reoperation rate of 20% to 33% within 18 months to five years. 24 Contraindications include pregnancy, active uterine or adnexal infections, allergy to intravenous contrast media, and renal insufficiency. The most common complication is postembolization syndrome, which is characterized by mild fever and pain, and vaginal expulsion of fibroids. 63

There is insufficient evidence on the effect of uterine artery embolization on future fertility. An observational study of 26 women treated with uterine artery embolization and 40 treated with hysterectomy found no difference in live birth rates. 42 In a retrospective study with five years of follow-up in women who received uterine artery embolization for fibroids, 27 (4.2%) had one (n = 20) or more (n = 7) pregnancies after uterine artery embolization. 64 Of these pregnancies, there were 15 miscarriages and 19 live births, 79% of which were cesarean deliveries because of complications. Further studies are needed on fertility outcomes after uterine artery embolization so that patients can be counseled appropriately.

Myolysis . Myolysis is a minimally invasive procedure targeting the destruction of fibroids via a focused energy delivery system such as heat, laser, or more recently, magnetic resonance–guided focused ultrasound surgery (MRgFUS). A study of 359 women treated with MRgFUS showed improved scores on the Uterine Fibroid Symptoms Quality of Life questionnaire at three months that persisted for up to 24 months ( P < .001). 40 In another study comparing women who underwent MRgFUS with those who underwent total abdominal hysterectomy, the groups had similar improvement in quality-of-life scores at six months, but the MRgFUS group had significantly fewer complications (14 vs. 33 events; P < .0001). 65 In a five-year follow-up study of 162 women, the reoperative rate was 59%. 66 Overall, this less-invasive procedure is well tolerated, although risks include localized pain and heavy bleeding. 40 Spontaneous conception has occurred in patients after MRgFUS, but further studies are needed to examine its effect on future fertility. 67

This article updates a previous article on this topic by Evans and Brunsell. 68

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Two Case Reports of Fibroid Treatment with Ulipristal Acetate Before In Vitro Fertilization

• Published: 25 June 2021
• Volume 3 , pages 2332–2338, ( 2021 )

Cite this article

• Teresa Gastañaga-Holguera 1 ,
• Virginia González González   ORCID: orcid.org/0000-0002-4753-2384 1 ,
• Marta Calvo Urrutia 1 ,
• Isabel Campo Gesto 2 ,
• Marta Vidaurreta Lázaro 1 &
• Ignacio Cristóbal García 1  

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Uterine fibroids are common benign uterine neoplasms in women of reproductive age and pregnancy desire. Several surgical approaches for symptomatic fibroids are available, such as surgical or pharmacologic treatments. We report two cases of fibroids treatment with ulipristal acetate (UPA) in women with primary sterility. The first case reports a successful in vitro fertilization (IVF) after UPA as an alternative treatment to reduce the size of fibroids in a patient with two previous abdominal myomectomies, resulting in an evolutive pregnancy. The second patient is a clinical case of a successful IVF after UPA treatment in a patient with a submucous fibroid which induced myoma migration leading to its prolapse. Even though myomectomy appears to be the gold standard treatment for fibroids in women with reproductive desires, UPA treatment could be considered in those patients at high surgical risk, although more clinical series are needed to establish the safety of UPA as treatment in those women.

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Ulipristal acetate before in vitro fertilization: efficacy in infertile women with submucous fibroids

Comparison of the influence of three fibroid treatment options: supracervical hysterectomy, ulipristal acetate and uterine artery embolization on ovarian reserve – an observational study

Uterine Fibroids and Effect on Fertility

Abbreviations.

controlled ovarian stimulation

European Medicines Agency

follicular-stimulating hormone

human chorionic gonadotropin

human menotropin hormone

international units

in vitro fertilization

magnetic resonance image

recombinant FSH

uterine artery embolization

ulipristal acetate

ultrasound scan

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The authors would like to thank the colleagues who assisted the patients during their pregnancies.

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Gynecology and Obstetrics Department, Assisted Reproduction Unit, Hospital Clínico San Carlos, Calle del Prof Martín Lagos, s/n, 28040, Madrid, Spain

Teresa Gastañaga-Holguera, Virginia González González, Marta Calvo Urrutia, Marta Vidaurreta Lázaro & Ignacio Cristóbal García

Gynecology and Obstetrics Department, Prenatal Diagnosis Unit, Hospital Clínico San Carlos, Madrid, Spain

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T.G.H., M.C.U., I.C.G., M.V.L., and I.C.G. contributed to patients’ healthcare and the collection of the data. T.G.H. and V.G.G. contributed to writing the manuscript. All authors contributed to revising the manuscript and approved the final version.

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Gastañaga-Holguera, T., González González, V., Calvo Urrutia, M. et al. Two Case Reports of Fibroid Treatment with Ulipristal Acetate Before In Vitro Fertilization. SN Compr. Clin. Med. 3 , 2332–2338 (2021). https://doi.org/10.1007/s42399-021-01003-1

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Accepted : 16 June 2021

Published : 25 June 2021

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DOI : https://doi.org/10.1007/s42399-021-01003-1

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• Ulipristal acetate
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Diffusion-weighted imaging as a potential non-gadolinium alternative for immediate assessing the hyperacute outcome of MRgFUS ablation for uterine fibroids

Affiliations.

• 1 Center of MRgFUS, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, No.6 Qinren Road, Foshan, 528000, Guangdong, China. [email protected].
• 2 Center of MRgFUS, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, No.6 Qinren Road, Foshan, 528000, Guangdong, China.
• 3 Chancheng High-Tech District Hospital of Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong, China.
• 4 Department of Gynecology, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, 528000, Guangdong, China.
• PMID: 38684835
• PMCID: PMC11058248
• DOI: 10.1038/s41598-024-60693-4

The aim of this study was to investigate the value of diffusion-weighted imaging (DWI) as a potential non-gadolinium alternative for promptly assessing the hyperacute outcome of magnetic resonance-guided focused ultrasound (MRgFUS) treatment for uterine fibroids. In this retrospective study we included 65 uterine fibroids from 44 women, who underwent axial DWI (b-value: 800 s/mm 2 ) and contrast-enhanced (CE) MR within 15 min post-ablation. Two blinded observers independently reviewed the DWI findings of ablated necrotic lesions and measured their volumes on DWI and CE images. The post-ablation DWI images revealed clear depiction of ablative necrotic lesions in all fibroids, which were classified into two types: the bull's eye sign (type 1) and the bright patch sign (type 2). The inter-observer intraclass correlation coefficient for classifying DWI signal types was 0.804 (p < 0.001). Volumetric analysis of ablated necrosis using DWI and CE T1-weighted imaging showed no significant variance, nor did the non-perfused volume ratios (all p > 0.05). Bland-Altman analysis revealed a mean difference of 2.38% and 1.71% in non-perfused volume ratios between DWI and CE, with 95% limits of agreement from - 19.06 to 23.82% and - 18.40 to 21.82%, respectively. The findings of this study support the potential of DWI as a viable non-gadolinium alternative for evaluating the hyperacute outcomes of MRgFUS ablation in uterine fibroids.

© 2024. The Author(s).

Publication types

• Research Support, Non-U.S. Gov't
• Contrast Media
• Diffusion Magnetic Resonance Imaging* / methods
• High-Intensity Focused Ultrasound Ablation* / methods
• Leiomyoma* / diagnostic imaging
• Leiomyoma* / pathology
• Leiomyoma* / surgery
• Middle Aged
• Retrospective Studies
• Treatment Outcome
• Uterine Neoplasms / diagnostic imaging
• Uterine Neoplasms / pathology
• Uterine Neoplasms / surgery

• Patient Care & Health Information
• Diseases & Conditions
• Uterine fibroids

Uterine fibroids are common growths of the uterus. They often appear during the years you're usually able to get pregnant and give birth. Uterine fibroids are not cancer, and they almost never turn into cancer. They aren't linked with a higher risk of other types of cancer in the uterus either. They're also called leiomyomas (lie-o-my-O-muhs) or myomas.

Fibroids vary in number and size. You can have a single fibroid or more than one. Some of these growths are too small to see with the eyes. Others can grow to the size of a grapefruit or larger. A fibroid that gets very big can distort the inside and the outside of the uterus. In extreme cases, some fibroids grow large enough to fill the pelvis or stomach area. They can make a person look pregnant.

Many people have uterine fibroids sometime during their lives. But you might not know you have them, because they often cause no symptoms. Your health care professional may just happen to find fibroids during a pelvic exam or pregnancy ultrasound.

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• Fibroid locations

There are three major types of uterine fibroids. Intramural fibroids grow within the muscular uterine wall. Submucosal fibroids bulge into the uterine cavity. Subserosal fibroids project to the outside of the uterus. Some submucosal or subserosal fibroids may be pedunculated. This means they hang from a stalk inside or outside the uterus.

Many people who have uterine fibroids don't have any symptoms. In those who do, symptoms can be influenced by the location, size and number of fibroids.

The most common symptoms of uterine fibroids include:

• Heavy menstrual bleeding or painful periods.
• Longer or more frequent periods.
• Pelvic pressure or pain.
• Frequent urination or trouble urinating.
• Growing stomach area.
• Constipation.
• Pain in the stomach area or lower back, or pain during sex.

Rarely, a fibroid can cause sudden, serious pain when it outgrows its blood supply and starts to die.

Often, fibroids are grouped by their location. Intramural fibroids grow within the muscular wall of the uterus. Submucosal fibroids bulge into the uterine cavity. Subserosal fibroids form on the outside of the uterus.

When to see a doctor

See your doctor if you have:

• Pelvic pain that doesn't go away.
• Heavy or painful periods that limit what you can do.
• Spotting or bleeding between periods.
• Trouble emptying your bladder.
• Ongoing tiredness and weakness, which can be symptoms of anemia, meaning a low level of red blood cells.

Get medical care right away if you have severe bleeding from the vagina or sharp pelvic pain that comes on fast.

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The exact cause of uterine fibroids isn't clear. But these factors may play roles:

• Gene changes. Many fibroids contain changes in genes that differ from those in typical uterine muscle cells.

Hormones. Two hormones called estrogen and progesterone cause the tissue the lines the inside of the uterus to thicken during each menstrual cycle to prepare for pregnancy. These hormones also seem to help fibroids grow.

Fibroids contain more cells that estrogen and progesterone bind to than do typical uterine muscle cells. Fibroids tend to shrink after menopause due to a drop in hormone levels.

• Other growth factors. Substances that help the body maintain tissues, such as insulin-like growth factor, may affect fibroid growth.
• Extracellular matrix (ECM). This material makes cells stick together, like mortar between bricks. ECM is increased in fibroids and makes them fibrous. ECM also stores growth factors and causes biologic changes in the cells themselves.

Doctors believe that uterine fibroids may develop from a stem cell in the smooth muscular tissue of the uterus. A single cell divides over and over. In time it turns into a firm, rubbery mass distinct from nearby tissue.

The growth patterns of uterine fibroids vary. They may grow slowly or fast. Or they might stay the same size. Some fibroids go through growth spurts, and some shrink on their own.

Fibroids that form during pregnancy can shrink or go away after pregnancy, as the uterus goes back to its usual size.

Risk factors

There are few known risk factors for uterine fibroids, other than being a person of reproductive age. These include:

• Race. All people of reproductive age who were born female could develop fibroids. But Black people are more likely to have fibroids than are people of other racial groups. Black people have fibroids at younger ages than do white people. They're also likely to have more or larger fibroids, along with worse symptoms, than do white people.
• Family history. If your mother or sister had fibroids, you're at higher risk of getting them.
• Other factors. Starting your period before the age of 10; obesity; being low on vitamin D; having a diet higher in red meat and lower in green vegetables, fruit and dairy; and drinking alcohol, including beer, seem to raise your risk of getting fibroids.

Complications

Uterine fibroids often aren't dangerous. But they can cause pain, and they may lead to complications. These include a drop in red blood cells called anemia. That condition can cause fatigue from heavy blood loss. If you bleed heavily during your period, your doctor may tell you to take an iron supplement to prevent or help manage anemia. Sometimes, a person with anemia needs to receive blood from a donor, called a transfusion, due to blood loss.

Pregnancy and fibroids

Often, fibroids don't interfere with getting pregnant. But some fibroids — especially the submucosal kind — could cause infertility or pregnancy loss.

Fibroids also may raise the risk of certain pregnancy complications. These include:

• Placental abruption, when the organ that brings oxygen and nutrients to the baby, called the placenta, separates from the inner wall of the uterus.
• Fetal growth restriction, when an unborn baby doesn't grow as well as expected.
• Preterm delivery, when a baby is born too early, before the 37th week of pregnancy.

Researchers continue to study the causes of fibroid tumors. More research is needed on how to prevent them, though. It might not be possible to prevent uterine fibroids. But only a small percentage of these tumors need treatment.

You might be able to lower your fibroid risk with healthy lifestyle changes. Try to stay at a healthy weight. Get regular exercise. And eat a balanced diet with plenty of fruits and vegetables.

Some research suggests that birth control pills or long-acting progestin-only contraceptives may lower the risk of fibroids. But using birth control pills before the age of 16 may be linked with a higher risk.

Uterine fibroids care at Mayo Clinic

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• Kellerman RD, et al. Uterine leiomyomas. In: Conn's Current Therapy 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed March 29, 2023.
• Extracellular matrix. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/extracellular-matrix. Accessed March 31, 2023.
• FAQs: Uterine fibroids. American College of Obstetricians and Gynecologists. https://www.acog.org/womens-health/faqs/uterine-fibroids. Accessed March 29, 2023.
• Kaunitz AM. Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management. https://www.uptodate.com/contents/search. Accessed March 29, 2023.
• Laparoscopic power morcellators. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/surgery-devices/laparoscopic-power-morcellators. Accessed March 29, 2023.
• Bradley LD, et al. Clinical performance of radiofrequency ablation for treatment of uterine fibroids: Systematic review and meta-analysis of prospective studies. Journal of Laparoendoscopic & Advanced Surgical Techniques. 2019; doi:10.1089/lap.2019.0550.
• AskMayoExpert. Uterine fibroids. Mayo Clinic; 2022.
• Jarell JF, et al. No. 164-Consensus guidelines for the management of chronic pelvic pain. Journal of Obstetrics and Gynaecology Canada. 2018; doi:10.1016/j.jogc.2018.08.015.
• Warner KJ. Allscripts EPSi. Mayo Clinic, Rochester, Minn. May 2, 2019.
• Burnett TL (expert opinion). Mayo Clinic. April 6, 2023.
• Lonnerfors C. Robot-assisted myomectomy. Best Practice and Research: Clinical Obstetrics and Gynaecology. 2018; doi:10.1016/j.bpobgyn.2017.09.005.
• Pfisterer K, et al. The extracellular matrix in skin inflammation and infection. Frontiers in Cell and Developmental Biology. 2021; doi:10.3389/fcell. 2021.682414 .
• Kohn JR, et al. Pregnancy after endometrial ablation: A systematic review. BJOG. 2018; doi:10.1111/1471-0528.14854.
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• Mayo Clinic Minute: Black women and uterine fibroids July 28, 2022, 03:30 p.m. CDT
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Clinical & Case Studies

Uterine fibroid treatment.

Clinical Studies

Questions? Give us a call!

Dallas: T 214-838-6440 • F 214-838-6441

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>> Society of Interventional Radiology: Minimally-Invasive Uterine Fibroid Treatment Safer and as Effective as Surgical Treatment

>> Radiology Journal: Uterine Fibroid Embolization Helps Restore Fertility

>> Society of Interventional Radiology: Minimally-Invasive, Less Expensive Treatment for Uterine Fibroids Underutilized

>> Uterine Artery Embolization: A Treatment Option for Symptomatic Fibroids in Postmenopausal Women

>> Uterine Artery Embolization in Patients with Large Fibroid Burden: Long-Term Clinical and MR Follow-up

>> Cost and Distribution of Hysterectomy and Uterine Artery Embolization in the United States: Regional/Rural/Urban Disparities

>> Nonsurgical Fibroid Treatment: Research Shows Improved Sexual Desire, Function

>> Long-term Risk of Fibroid Recurrence After Laparoscopic Myomectomy

Case Study: Jasmine

Jasmine, a 44-year-old Black woman, faced debilitating and life-changing symptoms from her uterine fibroids. Her symptoms included heavy menstrual bleeding, prolonged periods that lasted 2 weeks, and passing clots that led her to use Depends or a full box of sanitary pads each day. Because of the heavy blood loss, Jasmine experienced extreme anemia that landed her in the hospital. She had become so weak she needed a blood transfusion, which she had also needed a few years earlier. At that time, she had been diagnosed with fibroids and was told she needed a hysterectomy to resolve her symptoms.

Those are frightening words for any woman to hear. Jasmine was worried, not just because of the thought of surgery, but because she was unable to take time off work. The idea of not being treated; however, was just as daunting. In addition to the heavy bleeding, she also had painful cramps with her periods, pelvic pressure and back pain that was only getting worse.

Jasmine finally decided she had suffered enough and wanted to find a viable treatment option for her uterine fibroids. That is when she found Dallas fibroid specialist Dr. Suzanne Slonim and Fibroid Institute Dallas. She was tearful during her first visit as she was unsure that she could afford treatment for her fibroids. She had four children and no intention to get pregnant again.

After evaluating Jasmine’s personal and medical history, Dr. Slonim recommended Uterine Fibroid Embolization (UFE) as the best treatment option. Jasmine was happy to learn that we could perform the procedure in our office and that she could go home the same day, reducing costs, the risk of complications and recovery time. Furthermore, her health insurance covered the UFE procedure which made this treatment option affordable to her.  For the first time Jasmine sensed hope.

After Dr. Slonim completed the procedure, Jasmine’s symptoms slowly began to improve. At her last follow-up visit 4 months post UFE, her menstrual flow was down to 5 days, she was no longer passing clots, her pelvic pressure and back pain were gone, and her menstrual cramps were much improved.

Two years after her UFE treatment at the Fibroid Institute, she hasn’t needed another blood transfusion, she’s no longer anemic, and she has no need to wear Depends again. Jasmine is grateful to have her health and life back.

Refer a Patient for UFE with Fibroid Institute

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Does vitamin D play a role in uterine fibroids? A case control study

Panacea Journal of Medical Sciences

Uterine fibroids are monoclonal tumors of uterine smooth muscle cells. They are found in 20-40% of females in the reproductive age group. Ovarian hormones play an important role in its etiology. Recent studies have shown that low serum 25(OH)vitamin D levels are associated with increased risk of uterine fibroids. To investigate the association between serum vitamin D levels and uterine fibroids.A case control study was conducted in a tertiary care hospital among 183 women between the age of 18-50 years with uterine fibroids who attended obstetrics and gynecology department and 183 women of the same age group who had no uterine fibroids attending comprehensive health checkup clinic. Serum 25(OH)vitamin D levels were estimated in both groups by electrochemiluminescence immunoassay.Statistical analysis was performed using IBM SPSS version 20.0. P value of &lt;0.05 was considered statistically significant. The mean serum 25(OH) vitamin D levels of women with uterine fibroids were 15.03 ...

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New Study Finds the Best (and Worst) Foods to Help Prevent Uterine Fibroids

Here’s what you can do to help prevent and treat this condition.

Uterine fibroids are one of the most common benign tumors in women of reproductive age. They also disproportionately affect women of color. But just because they’re benign does not mean they can’t have some negative consequences that affect quality of life. 

While not all of those affected will experience symptoms, according to the U.S. Department of Health & Human Services Office on Women’s Health , they can vary from heavy bleeding, frequent urination and painful intercourse to lower back pain, enlarged lower abdomen and infertility. Uterine fibroids can also cause complications during pregnancy and labor—those with uterine fibroids have a six-times greater chance of having a c-section.

Known risk factors for uterine fibroids include age, race, BMI, pregnancy history, hypertension, vitamin D levels, hormonal imbalances and exposure to endocrine-disrupting chemicals (EDCs). There is some recent research that suggests that exposure to these chemicals during childhood may reprogram myometrial stem cells, contributing to uterine fibroid development.

Genetic factors and lifestyle choices, such as diet and stress levels, can also play a role. 

Typically, uterine fibroids are treated by removing them from the uterine wall in a procedure called myomectomy. If the fibroids come back or continue to be a problem, some opt for a partial hysterectomy in which the uterus is removed. 

But these treatments are invasive, expensive and carry potential complications. 

What if there was a way to prevent uterine fibroids from occurring to begin with? A new review study published on March 12, 2024 in the journal Nutrients suggests there may be. 

What Did This Review Study Show?

This review looked at almost 200 studies to develop evidence-based recommendations for what they coined LIFE UP awareness (Lifestyle Interventions, Food Modifications, and Environmental Practices for Uterine Fibroid Prevention).

As with any other health issue, the study authors state that prevention efforts should focus on promoting healthy behaviors and lifestyle choices, including eating nutritious foods, promoting physical activity, reducing tobacco and alcohol use, and enhancing stress management skills.

Starting with dietary choices, they found that fiber-rich vegetables, such as leafy greens, cruciferous vegetables, carrots, sweet potatoes and bell peppers, along with fruits like berries, citrus fruits, apples, pineapple and kiwi may play a role in uterine fibroid prevention. 

Related: 10 Amazing Health Benefits of Fiber

Study authors also underscore the importance of including nutrients like omega-3 fatty acids from fish, EGCG (found in green tea), vitamin D and poultry products as essential in a uterine fibroid prevention diet.

The researchers also found evidence that there may be a link between inflammation-calming herbs, spices and natural compounds and a reduction in uterine fibroids. Some of the ones they mention include curcumin (found in turmeric), resveratrol (found in peanuts and grapes), quercetin (found in onions, berries and broccoli), sulforaphane (found in cruciferous vegetables), anthocyanins (found in berries) and lycopene (found in tomatoes, carrots, papaya and watermelon). 

In addition, they also found evidence of individual links between vitamin A, selenium, magnesium and probiotics and reduced risk of uterine fibroids. 

Managing your stressors can also be important in uterine fibroid prevention. In their literature review, the study authors found research that suggests that chronic psychological stress may increase the risk of uterine fibroids by 24%. The reason this may occur is due to a domino effect that starts in certain hormone-producing glands and the hormones they produce that affect reproductive organs. 

There is also evidence that being physically active may decrease the risk of uterine fibroids. The study authors found research that suggests that those who engaged in at least four hours of vigorous physical activity per week were more likely to experience a decreased risk of uterine fibroids.

They also found a link between having a higher BMI and the risk of uterine fibroids, and suggest that studies back up the recommendation of regular physical activity and a balanced diet for helping to reduce the risk. 

In their literature review, these researchers also found foods to limit due to their association with increased risk for uterine fibroids. This includes red meat , high-fat dairy products, caffeine and alcohol. Researchers do note that more research needs to be done with each of these to strengthen the correlation between them and uterine fibroids. 

In addition to limiting certain foods, researchers state there is evidence that suggests certain chemicals act as hormone disruptors and should be avoided. This includes phthalates, which can be found in certain plastic bottles, including disposable water bottles and shampoo and conditioner bottles. Because there is some evidence that children exposed to these chemicals may end up with health issues—like uterine fibroids—into adulthood, it’s never too early to start reducing the use of plastic that contains these chemicals.

The Bottom Line

Uterine fibroids are common. And while they are typically benign, they can still negatively affect quality of life and fertility. As with health in general and other chronic conditions, eating a variety of nutritious foods—especially foods with anti-inflammatory benefits—engaging regularly in physical activity, managing stressors—including getting enough quality sleep—maintaining a healthy weight and a healthy gut microbiome may all go a long way in preventing uterine fibroids—and in treating them if you already have them.

Read the original article on Eating Well .

• Case Report
• Open access
• Published: 27 April 2024

Minimally invasive treatment of uterine necrosis with favorable outcomes: an uncommon case presentation and literature review

• Tengge Yu 1  

BMC Women's Health volume  24 , Article number:  267 ( 2024 ) Cite this article

210 Accesses

Metrics details

Uterine necrosis is a rare condition and is considered a life-threatening complication. However, cases of uterine necrosis were rarely reported, particularly those caused by infection. In terms of treatment, no minimally invasive treatment for uterine necrosis has been reported, and total hysterectomy is mostly considered as the treatment option.

The article specifically focuses on minimally invasive treatments and provides a summary of recent cases of uterine necrosis.

Case presentation

We report the case of a 28-year-old patient gravid 1, para 0 underwent a cesarean section after unsuccessful induction due to fetal death. She presented with recurrent fever and vaginal discharge. The blood inflammation markers were elevated, and a CT scan revealed irregular lumps with low signal intensity in the uterine cavity. The gynecological examination revealed the presence of gray and white soft tissue, approximately 5 cm in length, exuding from the cervix. The secretions were found to contain Fusobacterium necrophorum, Escherichia coli, and Proteus upon culturing. Given the patient’s sepsis and uterine necrosis caused by infection, laparoscopic exploration uncovered white pus and necrotic tissue openings in the anterior wall of the uterus. The necrotic tissue was removed during the operation, and the uterus was repaired. Postoperative pathological findings revealed complete degeneration and necrosis of fusiform cell-like tissue. Severe uterine necrosis caused by a multi-drug resistant bacterial infection was considered after the operation. She was treated with antibiotics for three weeks and was discharged after the infection was brought under control. The patient expressed satisfaction with the treatment plan, which preserved her uterus, maintained reproductive function, and minimized the extent of surgery.

Based on the literature review of uterine necrosis, we found that it presents a potential risk of death, emphasizing the importance of managing the progression of the condition. Most treatment options involve a total hysterectomy. A partial hysterectomy reduces the extent of the operation, preserves fertility function, and can also yield positive outcomes in the treatment of uterine necrosis, serving as a complement to the overall treatment of this condition.

Peer Review reports

Uterine necrosis is a rare complication. Several cases of uterine necrosis have been reported following embolization of the uterine arteries for postpartum hemorrhage or uterine fibroids, or as a result of severe endometritis [ 1 ]. Symptoms of uterine necrosis caused by infection typically include lower abdominal pain, fever, and foul-smelling vaginal discharge. When the infection affects the tissue surrounding the uterus, the uterus becomes enlarged and tender, and the edema of the inflamed tissue holds the uterus in place. Some complications may occur infrequently, including peritonitis, pelvic vein thrombosis, pulmonary embolism, pelvic abscess, sepsis, kidney damage, and even death. Diagnosis is usually based on clinical symptoms and physical examination. Inflammatory markers, imaging studies, and secretion cultures can also assist in the diagnosis. Hysteronecrosis is typically treated with a total hysterectomy. Most patients recover, and only a small number of patients do not survive. We reported a case of uterine necrosis caused by infection. We removed part of the uterus instead of performing a total hysterectomy. The patient recovered well. Few cases of uterine necrosis have been reported, and no one has reported minimally invasive treatment for it. Given the rarity of the case and the lack of minimally invasive treatment options for uterine necrosis, this report was written in conjunction with a literature review summarizing similar cases of uterine necrosis.

We report the case of a 28-year-old patient who was gravid 1, para 0, with no significant medical history. The patient is Asian, from the Han ethnic group, China’s largest ethnic group. When she was 32 weeks pregnant, intrauterine fetal demise was confirmed by ultrasound. A cesarean section was performed due to the difficulty of vaginal trial labor following a lateral perineal incision, which was necessary because the fetus’s shoulder was exposed. After the operation, the patient continued to experience a high fever, with a maximum temperature of 39.5 degrees Celsius, and the fat around the abdominal incision has become liquefied. The number of patient’s pulses was 140, respiratory rate was 22 times per minute, and blood pressure was 131/87mmhg. After receiving treatment with medications such as Tienam and Piperacillin, the patient’s body temperature and inflammation returned to normal, and she was discharged from Municipal integrated traditional Chinese and Western medicine hospital. The type of antibiotic Tienam is Carbapenem antibiotics, and the dose is 500 mg by injection three times a day. The type of antibiotic Piperacillin is semi-synthetic penicillin antibiotics, and the dose is 1.5 g by injection three times a day. The disease subside after 7 days treatment.

A week later, she was admitted to Municipal integrated traditional Chinese and Western medicine hospital for the second time due to fever and pain in her lower left abdomen. The patient’s heart rate was normal, respiratory rate was 20 times per minute, and blood pressure was 121/80mmhg. The blood inflammation index was elevated, indicated by a C-reactive protein level of 52.01 mg/L. Brain CT and lung CT scans revealed no significant abnormalities. She was discharged after two weeks of treatment with medications such as Tienam and Piperacillin with the same dose as last time. The disease subside after 5 days treatment.

Five days later, she was admitted to our hospital for the third time due to a recurring fever, accompanied by vaginal purulent discharge and odor. The patient’s heart rate was 110 times per minute, respiratory rate was 23 times per minute, and blood pressure was 132/85mmhg. There was no increase in β-HCG, white cell count was 12.3 × 10^9 /L in the differential blood count, hemoglobin was 104 g/L, and procalcitonin was 0.12 ng/ml. She felt feverish and lethargic, with mild nausea. The patient was treated orally with Moxifloxacin by 1 tablet once a day for 3 days. A vaginal color ultrasound revealed a hypoechoic area in front of the uterus, indicating encapsulated effusion. The ultrasound also revealed an abnormal uterine echo, uneven uterine enlargement with abundant blood supply, trace effusion of the cervical canal, and pelvic effusion. The enhanced CT scan revealed swelling and adhesion of the anterior wall of the uterus and the adjacent anterior abdominal wall, along with changes in the surrounding exudate. Additionally, a lumpy, uneven low signal shadow was observed in the uterine cavity, along with visible pelvic fluid (Fig.  1 ). The histopathological analysis of intrauterine effluents revealed degenerative smooth muscle tissue accompanied by pus. Anaerobic culture of cervical secretions suggested the presence of Fusobacterium necrophorum. Biopsy of cervical and vaginal lesions revealed complete necrosis of fusiform cell-like tissue, with increased infiltration of inflammatory cells, and no identifiable endometrial tissue. Due to the presence of pus in the uterus, morinidazole was administered, and uterine drainage was performed. However, the result was not favorable. A gynecological examination revealed the presence of necrotic tissue in the vagina, extending approximately 5 cm from the cervical opening. The tissue appeared white and emitted a foul odor. It was recommended to undergo a laparoscopic surgery.

Sagittal computed tomography images. The uterus shows heterogeneous spongiform enlargement with multiple air locules, measuring 4 × 2.6 cm and extending over 5 cm. We have observed a difficulty in distinguishing between the myometrium and the endometrial cavity

Given that the patient had strong fertility requirements, the surgical procedure included laparoscopic necrotic tissue excision, uterine reconstruction, and the uterine drainage tube placement. During the laparoscopy, adhesion of the uterus to the anterior wall of the abdomen was observed. An opening with white pus and necrotic tissue was visible in the anterior wall of the uterus. The necrotic tissue in the cavity was removed during the operation (Fig.  2 Fig.  3 ). Cefoxitin (1.5 g tid ivgtt) and ornidazole (500 mg bid oral) were administered postoperatively to prevent infection for 2 days. After the surgery, the patient developed a fever with a peak body temperature of 39.3 degrees Celsius, which prompted a switch to cefoperazone-sulbactam sodium (2 g bid ivgtt) and ornidazole antibiotics (500 mg bid oral) for 7 days. After the body temperature returned to normal, the antibiotics were downgraded, the uterine drainage tube was removed, and oral antibiotics were continued after discharge. The results of the vaginal secretion culture indicated the presence of Escherichia coli and Proteus bacteria. The pathological results revealed extensively denatured necrotic tissue with calcification and heightened inflammatory cell infiltration.

The images seen during the surgery. The necrotic tissue of the uterus, attached to the anterior wall of the abdomen, is clearly visible in gray and white colors. It is situated in the anterior wall of the uterus and is connected to the uterine cavity

The gross specimen appeared gray in color, with an extremely soft texture, measuring about 5 cm in length, and accompanied by a foul odor

Uterine necrosis is a rare and serious complication. Cases of uterine necrosis have been reported in the literature as a complication of cesarean section, embolization for postpartum hemorrhage, or for a leiomyomatous uterus, as well as in cases of severe endometritis [ 2 , 3 , 4 , 5 , 6 , 7 ] (Table  1 ). Several authors have described cases of uterine necrosis associated with intrapartum or postpartum complications that increase the risk of infection. The literature reports cases of uterine necrosis resulting from the placement of B-Lynch compression sutures, uterine artery embolization, or surgical ligation techniques used to treat postpartum hemorrhage. These procedures may increase the risk of infection as the tissue becomes devascularized. A. Fouad et al. described a case similar to ours in which a patient underwent a cesarean section due to fetal death, followed by postoperative sepsis and purulent uterine necrosis. Despite undergoing a hysterectomy, the disease continued to progress and ultimately resulted in death due to septic shock and multiple organ failure.

The case we report has identified pathogenic bacteria in the culture, which is significant for diagnosing infection-induced uterine necrosis. Fusobacterium necrophorum is a pleomorphic, Gram-negative, non-spore-forming obligate anaerobic coccobacillus. It is associated with localized abscesses, throat infections, and life-threatening systemic diseases. It is a common resident of the oral cavity and the vagina. Of the two subspecies of Fusobacterium necrophorum, biovar B is the primary pathogen for humans. Potential virulence factors include cell wall endotoxin lipopolysaccharide, hemagglutinin, and hemolysin. Most reported cases related to gynaecology occurred in the postpartum or post-abortion period, in addition to a few reports associated with the use of intrauterine devices, tubo-ovarian abscesses, and gynecological Lemierre’s syndrome [ 8 , 9 , 10 ]. Although infected with the same pathogen, the case reported by T. Widelock et al. developed more severe symptoms, including lung abscesses and kidney failure, as a result of hematoplasm infection [ 11 , 12 , 13 ].

A pelvic ultrasound is the initial diagnostic test that can reveal signs of uterine necrosis. The uterine cavity is typically expanded and exhibits multiple echogenic foci with accompanying dirty acoustic shadowing. Little or no vascularity is observed [ 14 ]. The diagnosis requires further exploration through a CT scan or MRI, as these are the preferred methods of investigation. The CT scan is highly useful for diagnosis as it demonstrates the presence of gas in the myometrium, the lack of enhancement of the myometrium after contrast injection associated with uterine enlargement, and the presence of free fluid in the peritoneal space [ 15 , 16 ].

Since uterine necrosis is described as a life-threatening complication, it is suggested to manage it with hysterectomy and broad-spectrum antibiotic therapy [ 17 , 18 ]. But sometimes it’s a case-by-case situation.

Avoid the chances of associated infections by systematic vaginal sampling in the third trimester, and promote good asepsis during surgery and antibiotic coverage in case of doubt about any undiagnosed prepartum infection, which may potentiate hypoxia and the risk of necrosis. Uterine necrosis may be secondary to all these intertwined factors and could be potentiated by an environment of hypoxia, hypoperfusion, hypovolemia secondary to hemorrhage, massive transfusions with disadvantages in a patient who is immunocompromised by pregnancy, and possibly, by other vitamin and iron deficiencies.

Given the limited number of reported cases of uterine necrosis in the past, there is no standardized treatment protocol. However, due to the potential fatality of uterine necrosis, most treatment options involve total hysterectomy. In our case, only the necrotic tissue of the uterus was removed in young women who had not given birth, and the prognosis for the patient is good. This study also has limitations, including the short follow-up time and the small number of cases collected. It needs to be complemented by subsequent case reports related to uterine necrosis.

Data availability

No datasets were generated or analysed during the current study.

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Department of Gynecology and Obstetrics, West China Xiamen Hospital of Sichuan University, Xiamen, 361000, China

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Yu, T. Minimally invasive treatment of uterine necrosis with favorable outcomes: an uncommon case presentation and literature review. BMC Women's Health 24 , 267 (2024). https://doi.org/10.1186/s12905-024-03089-w

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Received : 21 December 2023

Accepted : 12 April 2024

Published : 27 April 2024

DOI : https://doi.org/10.1186/s12905-024-03089-w

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