A Rare Case of Spontaneous Heterotopic Pregnancy at 12 weeks of Gestation Following Natural Conception With Literature Review.

A 36-year-old woman presented for her first antenatal visit at a local primary care hospital at 7 weeks and 4 days of gestation, according to her own timeline. An ultrasound examination revealed an intrauterine pregnancy with no abnormalities in the bilateral adnexa. The pregnancy was a result of natural conception, and she had no previous risk factors for ectopic pregnancy. Ten years prior, she had a healthy vaginal delivery, and her previous pregnancies were uneventful. She reported a history of irregular menstruation, with cycles ranging from 25 to 45 days. She denied any significant medical history, previous surgeries, and did not smoke or drink alcohol. There was no notable family history of pelvic disease. Throughout her pregnancy, serial TVUS consistently indicated an intrauterine pregnancy. However, at 12 weeks of gestation, the patient was admitted due to sudden severe abdominal pain. Prior to admission, she experienced mild abdominal discomfort, which she initially attributed to normal pregnancy symptoms. She was advised to monitor her condition and seek medical attention only if her symptoms worsened. Unfortunately, as her condition progressed to severe abdominal pain, she presented to the hospital. On admission, her temperature was 36.5°C, heart rate was 76 beats per minute, and blood pressure was 93/70 mmHg. Physical examination revealed the patient was alert but pale, and her abdomen was rigid with signs of peritoneal irritation. A gynecological examination showed a smooth external genitalia and vaginal mucosa, with a clean cervix and uterus consistent with a 12-week size pregnancy; however, there was marked tenderness in the bilateral adnexa. An emergency ultrasound conducted at Jining No.1 People’s Hospital revealed a viable intrauterine pregnancy with a fetal heart rate of 166 beats per minute and a crown-rump length of 6.6 cm, corresponding to a gestational age of 12 weeks and 6 days ( Figure 1 ). An accumulation of free fluid measuring 8.7 cm × 7.5 cm × 5.4 cm, corresponding to an estimated volume of approximately 352 cm³, was noted in the rectouterine pouch. A thick-walled cystic structure in the right ovary measured 2.3 cm × 2.0 cm × 1.9 cm, with an estimated volume of about 8.7 cm³. Additionally, an irregular hypoechoic area beneath the right ovary measured 4.3 cm × 3.2 cm × 2.8 cm, corresponding to an estimated volume of approximately 38.5 cm³ ( Figure 2 ). Additionally, fluid collections were noted in both the right and left pelvic cavities as well as in the hepatorenal recess, suggesting a possible corpus luteum cyst or hematoma. Laboratory tests revealed a white blood cell count of 19.5 × 10 9 /L, hemoglobin of 113 g/L, hematocrit of 33.2%, and a beta-human chorionic gonadotropin (β-hCG) level of 57,278.00 mIU/mL. Figure 1 Ultrasonography image of the uterus showing an intrauterine gestation. Figure 2 An uneven hypo echo with a range of 4.3×3.2×2.8cm below the right ovary. Ultrasonography image of the uterus showing an intrauterine gestation. An uneven hypo echo with a range of 4.3×3.2×2.8cm below the right ovary. Given the suspicion of pelvic and abdominal bleeding, the hospital quickly activated a green channel for admission. The surgical team decided to proceed with an urgent diagnostic laparoscopy. Preoperative assessments were within normal limits. After being informed of the risks, the patient signed the consent form for surgery and was taken to the operating room. During the procedure, approximately 1200 cubic centimeter of non-echoic fluid was found in the rectouterine pouch, and the uterus was consistent with a 12-week pregnancy. The right fallopian tube was significantly dilated, measuring 3.5 cm in length, with thickened walls measuring 4.0×3.0 × 3.0 cm and an estimated volume of approximately 36.0 cm³. It exhibited a bluish-purple appearance with a 2 mm rupture site and active bleeding. The diagnosis was a ruptured right ectopic pregnancy causing hemorrhagic shock at an early stage of pregnancy. A right salpingectomy was performed, and the excised tissue was sent for pathological examination. The surgical procedure was completed without complications. Pathological analysis of the excised fallopian tube revealed structures consistent with an embryo. Postoperative β-hCG levels on the second and third days were 49,213 mIU/mL and 57,577 mIU/mL, respectively. On the second postoperative day, laboratory results showed a white blood cell (WBC) count of 7.85 × 10 9 /L, red blood cell (RBC) count of 3.02 million/μL, and hemoglobin of 95 g/L. The patient received blood transfusions and progesterone support (200 mg/day intravaginally) to support fetal health, and her postoperative course remained stable. She was discharged on the fourth postoperative day without any complications. During follow-up, she chose to undergo an elective termination of pregnancy at 14 weeks gestation for personal reasons.

Heterotopic pregnancy is a rare condition characterized by the simultaneous occurrence of an intrauterine pregnancy and an ectopic pregnancy. 1 The underlying factor for this phenomenon may be attributed to an ovulatory dysfunction or a variation in the migration rates of the two embryos. This could occur as a result of a delay in the fertilized egg being captured by the fallopian tube. This pathological condition is estimated to occur in approximately 1 in 30,000 pregnancies. 2 However, with the increasing use of assisted reproductive technologies and ovulation-stimulating medications, the incidence of heterotopic pregnancy has risen to about 1 in 3,900 pregnancies. 3 , 4 The risk factors associated with heterotopic pregnancy closely resemble those seen in ectopic pregnancies. These include smoking, a past occurrence of ectopic pregnancy, history of inflammatory pelvic disease, sexually transmitted infections (notably Chlamydia), surgical procedures involving the fallopian tubes, previous abdominal surgeries, endometriosis, infertility treatments, and certain contraceptive methods. 5 Patients with heterotopic pregnancy often present with symptoms such as a history of amenorrhea, abdominal pain, the presence of an abdominal mass, and vaginal bleeding. Due to the rarity of this condition, there are currently no universally accepted guidelines for its management. Currently, transvaginal ultrasound (TVUS) and 2D/3D ultrasound imaging play crucial roles in the initial assessment and diagnosis of heterotopic pregnancy. 6 , 7 TVUS is particularly advantageous in early pregnancy evaluation due to its higher resolution and ability to provide clearer images of pelvic structures compared to transabdominal ultrasound. Meanwhile, 2D and 3D ultrasound techniques enhance the visualization of the anatomical features of both intrauterine and ectopic pregnancies. However, the low sensitivity of these imaging modalities can still lead to challenges in early detection, resulting in missed or misdiagnosed cases. 8 Surgical intervention is typically required to manage heterotopic pregnancy, with the primary goal of removing the ectopic pregnancy while preserving the intrauterine pregnancy. 9 , 10 This case report presented a unique instance of spontaneous intrauterine pregnancy complicated by the rupture of a right fallopian tube ectopic pregnancy at 12 weeks of gestation, along with a comprehensive review of the relevant literature.

This case of heterotopic pregnancy is notable not only because it involves a viable intrauterine pregnancy but also due to the absence of typical risk factors associated with ectopic implantation. When a pregnant woman presents with acute abdominal pain, a comprehensive evaluation is essential. We emphasize that all pregnant patients with clinical signs such as abdominal pain, free fluid in the Douglas pouch, hypovolemic shock, or those classified as high-risk should undergo a thorough assessment of the adnexa. A diagnosis of ectopic pregnancy must be strongly considered, even in the presence of a confirmed intrauterine pregnancy. It is crucial to understand that confirmation of an intrauterine pregnancy through clinical evaluation or ultrasound does not rule out the possibility of a concurrent ectopic pregnancy. Timely surgical intervention is critical for the effective management of heterotopic pregnancies and can significantly improve outcomes for both the mother and the newborn.

Heterotopic pregnancy refers to the simultaneous presence of a pregnancy within the uterus and another pregnancy outside the uterus. 11 The condition results from the simultaneous implantation of multiple embryos, which are released from the ovaries and mature in the uterus. While heterotopic pregnancy is a rare and potentially life-threatening complication, it occurs in approximately 1 in 30,000 natural conceptions. 12 The risk factors for heterotopic pregnancy are similar to those of ectopic pregnancy and include adhesions, intrauterine devices, pelvic inflammatory illness, history of ectopic pregnancy, assisted reproductive technologies, and ovarian hyperstimulation syndrome. 5 However, as demonstrated in the case we reported, heterotopic pregnancy can also occur spontaneously, without the presence of these risk factors, making it an exceptionally rare and difficult condition to diagnose. In our case, menstrual irregularities were noted, which may be linked to underlying endocrine disturbances contributing to abnormal ovulation. A review of the literature on heterotopic pregnancies, involving the coexistence of an ectopic pregnancy and a viable intrauterine pregnancy, was conducted. The method was referred according to a previous study. 13 Using the search terms “spontaneous heterotopic pregnancy”, “outcomes” “diagnosis” ‘management’ in PubMed, Medline, and Google Scholar from 2020–2024, a total of 141 results were generated. After carefully analyzing all titles and abstracts, only studies in English, describing cases of heterotopic pregnancies with a coexisting viable intrauterine pregnancy, were included. A total of 25 papers reporting heterotopic pregnancy with intrauterine fetus were identified. 4 , 10 , 14–36 Detailed information, such as the demographics, clinical presentation, diagnostic methods, management strategies, and outcomes, was presented in Table 1 . The main presenting symptoms were abdominal or pelvic pain in 24 cases and vaginal bleeding in 10 cases, only one case presented no symptoms at all, which illustrated the diverse presentations of heterotopic pregnancy. This finding was consistent with our own case, where the patient presented with severe abdominal pain at 12 weeks of gestation. The variability in symptom presentation emphasized the diagnostic challenge of heterotopic pregnancy, especially when symptoms overlap with other pregnancy-related complications such as threatened miscarriage or ruptured corpus luteum cysts. Table 1 Included Articles in the Literature Review Authors and References Publish Year Ages (Years) Parity GA at Diagnosis (Weeks+Days) Pregnancy Complications Treatment Outcome Černiauskaitė M et al 14 2020 28 G1P0 7 Weakness, pain in lower abdomen and spotting bleeding LS Vaginal Maharjan S et al 15 2021 28 G1P0 8 Lower abdomen pain LS C/S Momtahan M et al 16 2021 31 G1P0 36+4 Labor pain, severe bleeding C/S +skin incision extended to T shape C/S Ouafidi B et al 17 2021 32 G3P3 9+2 Acute pelvic pain Laparotomy Vaginal Lober R et al 18 2024 36 6 Severe acute lower abdominal pain Laparoscopy Vaginal Valencia V et al 4 2024 37 G3P1 7 Vaginal bleeding and lower abdominal pain LS (-) Khouloud M et al 19 2024 36 G5P3 12 Persistent pelvic pain and abnormal vaginal bleeding Laparotomy Induced abortion Abdelmonem AH et al 20 2021 38 G5P4 9+5 Lower abdominal pain LS (-) Kathopoulis N et al 21 2023 26 G2P1 17 Lower abdominal pain Laparotomy C/S Maree G et al 22 2022 37 G7P6 12 Lower abdomen and intermittent Vaginal bleeding Laparotomy Induced abortion Aziz M et al 23 2020 28 G2P1 7 Abdominal, back and pelvic pain, dyspnea, chest pressure, chills, sweats, cough, rhinorrhea LS Induced abortion Tariq A et al 24 2024 34 G4P3 6+2 Delayed period Conservative treatment C/S Soecki G et al 25 2024 26 G2P1 9+6 Nausea and abdominal pain Drug therapy Death due to misdiagnose Dubbewar A et al 26 2020 40 (-) 12 Abdominal pain Salpingectomy Induced abortion Murewanhema G et al 27 2020 34 G3P2 12 Bleeding vaginally, mild backache, abdominal pain Laparotomy (-) Maduako KT et al 28 2022 25 G4P2 6 Acute abdominal pain, vomiting LS C/S Kajdy A et al 29 2021 24 26 Upper abdominal pain Salpingectomy C/S Julien A et al 30 2023 34 G3P2 8+1 & 5+4 Abdominal pain Laparoscopy (-) Bouab M et al 10 2024 28 G1P0 8 Acute pelvic pain, vaginal bleeding Laparotomy (-) Ntounis T et al 31 2021 43 G4P3 7 Abdominal pain and sudden-onset Vaginal bleeding Laparotomy C/S Dipanda AN et al 32 2021 22 G3P1 8 Pelvic + abdominal + shoulder pain Salpingectomy Spontaneous abortion Fomukong NH et al 33 2021 32 G3P2 7 Acute abdominal pain LS (-) Nkurunziza C et al 34 2020 34 G6P2 18 Abdominal pain, distended abdomen Subtotal hysterectomy Induced abortion Cucinella G et al 35 2021 25 G2P0 5+4 Abdominopelvic pain and vaginal bleeding Salpingectomy C/S Nguyen KP et al 36 2022 27 G4P1 5 Acute abdominal pain and vaginal bleeding LS Abortion Abbreviation : LS, laparoscopic salpingectomy; C/S, cesarean section; GA, gestational age; (-), missing. Included Articles in the Literature Review Abbreviation : LS, laparoscopic salpingectomy; C/S, cesarean section; GA, gestational age; (-), missing. The diagnosis of heterotopic pregnancy was often delayed, as it was difficult to distinguish from other conditions, such as early miscarriage or uncomplicated intrauterine pregnancies. 37 In the 25 cases reviewed, only 14 cases (56.00%) were diagnosed during the period of five to eight weeks of pregnancy, 3 cases (12.00%) were diagnosed between nine and ten weeks, and 8 cases (32.00%) were diagnosed after the eleventh week. The delayed diagnosis of heterotopic pregnancy, especially in spontaneous cases, highlighted a critical challenge in clinical practice. Imaging studies, particularly TVUS, were critical in identifying both the intrauterine pregnancy and the ectopic mass in these cases. However, TVUS has limitations in diagnosing heterotopic pregnancy, particularly when the intrauterine pregnancy is well visualized, potentially obscuring the ectopic pregnancy. It has been reported that TVUS has a sensitivity of 92.4% and a specificity of 100%. 38 According to a comprehensive assessment of the literature conducted between 2005 and 2010, up to 33% of heterotopic cases had previously had a routine sonography, which resulted in misplaced confidence and a misdiagnosis. 2 This highlighted the need for heightened clinical awareness and the use of advanced imaging techniques, such as 2D/3D ultrasound, which can offer clearer delineation of both the intrauterine and ectopic pregnancies. In addition to imaging, monitoring the patient’s serum β-hCG levels may provide helpful diagnostic clues. However, while elevated β-hCG levels are often associated with an intrauterine pregnancy, they can also be elevated in ectopic pregnancies, making the interpretation of β-hCG levels alone insufficient for a definitive diagnosis of heterotopic pregnancy. In our case, the patient had a β-hCG level of 57,278 mIU/mL at the time of presentation, which was consistent with the intrauterine pregnancy, but it also indicated the possibility of an ectopic pregnancy. As such, while β-hCG testing can support the diagnosis, it is not a standalone tool, and the use of TVUS or 2D/3D ultrasound remains paramount in clinical practice. The management approaches for heterotopic pregnancy varied widely across the studies, with several different approaches employed depending on the patient’s clinical condition, the stage of pregnancy, and the location of the ectopic pregnancy. 36 Surgical management is the most common intervention, with a variety of procedures utilized to treat the ectopic pregnancy and preserve the intrauterine pregnancy. In some cases, a salpingectomy was performed to remove the ectopic pregnancy, while others chose salpingostomy in an attempt to preserve the fallopian tube and the possibility of future fertility. The decision to terminate the intrauterine pregnancy was generally based on maternal health concerns, the size of the ectopic pregnancy, and the risks associated with carrying both pregnancies to term. Certainly, if there are no symptoms of abdominal bleeding, a conservative approach can be safely adopted, and the patient can be closely monitored. 1 In our study, given the diagnosis of a ruptured ectopic pregnancy with active bleeding and the presence of a viable intrauterine pregnancy, an urgent surgical intervention was necessary. We opted for laparoscopic salpingectomy under general anesthesia, which required the complete removal of the affected tube to ensure the patient’s safety and effectively control the hemorrhage. Following the surgical procedure, the patient was closely monitored and received progesterone support (200 mg/day intravaginally) to support fetal health. Meanwhile, pathological examination and serial measurement of β-hCG levels were performed, confirming the resolution of the ectopic pregnancy while the intrauterine pregnancy continued to progress normally. The patient’s recovery was uneventful, and no major complications, such as infection or excessive bleeding, were observed. Postoperatively, the patient was advised to continue regular follow-up visits to ensure the ongoing viability of the intrauterine pregnancy.