Intramural pregnancy (IMP) is defined as a fertilized egg that has implanted in the myometrium and surrounded by myometrial tissue [1] and not in direct communication with uterine endometrium. The incidence is less than 1/100 of pregnancies [2]. The common types of ectopic pregnancy are tubal pregnancy, cervical pregnancy, cornual pregnancy, ovarian pregnancy whilst intramural pregnancy is an uncommon type of ectopic pregnancy [3]. During intramural pregnancy the gestational sac is located within the muscular wall of the uterus and may present with symptoms of amenorrhea, abdominal pain, vaginal bleeding and hemorrhagic shock. The symptoms can be severe and acute, and can be confused with ectopic pregnancy and trophoblastic disease [4]. Intramural pregnancies are rare but dangerous, early diagnosis and timely treatment can reduce damage to the uterus, decrease the incidence of bleeding and protect a women’s fertility [5].

At present there are several therapeutic options for treatment of intramural pregnancy, both surgery and medication are available [6]. Pharmacological interventions include medication with mifepristone and methotrexate, mifepristone antagonizes progesterone and causes degeneration and necrosis of the meconium and chorion, methotrexate inhibits trophoblast cells and also kills the chorion and destroys embryonic tissue [7]. Several surgical methods have been reported, including transabdominal surgery, hysteroscopic surgery [8] and laparoscopic surgery [9]. Laparoscopic surgery has the benefit of less trauma and rapid postoperative recovery in addition to sutures in the myometrium that will reduce the risk of uterine rupture in a subsequent pregnancy [10]. Hysteroscopy can also be used to treat intramural pregnancy. The hook electrode can cut the endometrial layer and myometrium layer through the sinus tract and electrosurgery can cut the intramural pregnancy tissue. This method reduces the damage to the endometrium and is suitable for patients who wish to maintain fertility as hysteroscopy is also feasible for patients with implantation close to the endometrial layer. This manuscript analyzes the medical records of laparoscopic and hysteroscopic treatment of intramural pregnancy in our institution. A total of 12 patients with intramural pregnancy were collected and the advantages and disadvantages of laparoscopic and hysteroscopic treatment of intramural pregnancy were systematically evaluated.

In this study 12 patients had a history of uterine operations whilst 3 patients had never been pregnant. Two patients had a history of hysteroscopic surgery and the other 10 patients had one or more previous pregnancies. Six patients conceived by embryo transfer. Six cases indicated cornual pregnancy with a gestational sac located within the myometrium near the cornu but separate from the endometrial lining as seen by 3D transvaginal ultrasound. The other 6 cases showed gestational sacs located in the lateral wall of uterus. All patients had successful laparoscopic removal of the chorionic tissue from the uterus. Average blood loss 50.9 $\pm$ 5.5 (mL), average hospital stay 5.4 $\pm$ 0.6 (days), average hospital cost 10,487 $\pm$ 548 (RMB) (Table 2).

The etiology of intramural pregnancy is unclear [11], according to available literature relevant factors include damaged or defective endometrium, induced abortion and cesarean delivery that can lead to endometrial injury [12]. The fertilized egg implants in the muscular wall or uterine scar of the damaged endometrium with the formation of a sinus tract and false canal due to previous uterine surgery. Many patients have a history of cesarean section and induced abortion [13]. Other causes include adenomyosis where the ectopic endometrium deep in myometrium produces metaphase morphology through estrogen and progesterone which becomes a potential site for egg implantation and the embryo enters the myometrium by an ectopic endometrial sinus [14]. In addition a defective uterine serous membrane as result of pelvic surgery and serious inflammation leads to the destruction of serous membrane. Once the zygote is free from the fallopian tube it travels in the pelvic cavity and is implanted in the uterine membrane defect and into the myometrium. During in vitro fertilization (IVF), a “false path to implantation” may be formed in the myometrium if the embryo transfer is difficult [15]. This allows the fertilized egg to implant in the myometrium and in our report, we identified 6 patients with a history of in vitro fertilization. Finally there is a hypothesis that trophoblast cell activity is enhanced and decidual defense is weakened resulting in ectopic pregnancy. All 12 patients in this study had at least one of the above risk factors, 6 patients had experienced an embryo transfer.

In the past, because of the special location of intramural pregnancy, it was not diagnosed until the occurrence of uterine rupture. In recent years with the development of ultrasound, especially the use of transvaginal ultrasound, it is possible to reach a timely diagnosis of this condition before surgery. We determined the following ultrasound features of intramural pregnancy: (1) the gestation sac was completely surrounded by the myometrium; (2) the endometrial cavity and fallopian tube were not connected. Three-dimensional ultrasound shows the relationship between the gestational sac and endometrial cavity, as well as the association of endometrial and uterine myometrium that allows a clear visualization of endometrial myometrial junction, and Color Doppler flow imaging shows abundant blood flow with low resistance [16].

There are several treatments for intramural pregnancy, including conservative treatment with methotrexate drug therapy, surgical methods including laparotomy, hysteroscopic and laparoscopic surgery, laparotomy which is rarely used due to the severity of the trauma and slow recovery [17]. For gestational sacs with small gestational age, small mass and thin serosal layer, laparoscopic removal of intrauterine pregnancy can be safely performed. Laparoscopic surgery is characterized by minimal trauma, rapid postoperative recovery, and the possibility of suturing the myometrial wound to reduce the risk of subsequent pregnancy rupture. Auer-schmidt reported hysteroscopic treatment for intramural pregnancy [8], as the hook electrode can cut the mucosa and muscle of uterus by the false tract, and gradually cut the pregnancy tissue between the muscle tissue walls, thus reducing the damage to the endometrium in those with future fertility needs. Hysteroscopic surgery is characterized by less trauma, less bleeding and faster recovery for those with pregnancy sac implantation close to the mucosa. In this paper, 5 patients were first selected for hysteroscopy, but the location of the gestational sac was not found during the procedure, so they were converted to laparoscopic surgery to open myometrium and successfully locate the sac and remove the chorionic villi.

We describe 12 extremely rare cases of ectopic pregnancy. According to statistics of the 12 patients, the average blood loss is 50.9 $\pm$ 5.46 (mL), average hospital stay is 5.36 $\pm$ 0.59 (days), and the average hospital cost is 10,487 $\pm$ 548 (RMB). Postoperative $\beta$-hCG values decreased significantly in all patients, with a decrease of more than 50%. For pregnancy sac with small gestational age, laparoscopy and hysteroscopy is a reliable treatment method with less trauma and faster postoperative recovery, the laparoscopic procedure allows for suturing of the myometrial wound, reducing the risk of uterine rupture in another pregnancy [18]. The uterus and reproductive function were preserved in all patients, and postoperative recovery was faster. Laparoscopic treatment of early intramural pregnancy is a safe and reliable procedure. Patients with fertility issues were not included in the statistics for this article. Future studies should include the fertility conception interval, and mode of delivery of these women in order to comprehensively evaluate the effectiveness of laparoscopy in the treatment of intramural pregnancy.

The datasets used during the current study are available from the corresponding author on reasonable request.

HX conceived of the study and wrote the article. JH collected the data and analyzed the data; BL conceived the topic of the article, design the paper structure, interpreted and analyzed the data, and edited the article. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of 044(2021). All participants gave written informed consent prior to entering the study.

We would like to express my gratitude to all those who helped me during the writing of this manuscript.

This research was funded by Women and Children’s Hospital of Chongqing Medical University, grant number 2020YJMS10. This research was funded by Chongqing Science and Technology Commission, grant number CSTB2022NSCQ-MSX0907.

The authors declare no conflict of interest.