Effectiveness and safety of ultrasound-guided intramuscular lauromacrogol injection combined with hysteroscopy in cervical pregnancy treatment: A case report

lNTRODUCTlON

Cervical pregnancy is a type of ectopic pregnancy associated with induced abortion, diagnostic curettage, cesarean section, spontaneous abortion, cervical surgery, and assisted reproductive technology[1,2]. It results in increased morbidity and is diagnosed in around 0.15% of all ectopic pregnancies[3]. A definite diagnosis in the early stages is challenging due to the specific onset site. It is commonly diagnosed by ultrasound because of vaginal bleeding[4], and is often accompanied by critical medical conditions. Surgery is the mainstay in the conventional management of cervical pregnancy, but tends to cause cervical adhesions and decreased function, resulting in the loss of natural fecundity. With significant advances in clinical diagnostic techniques and a growing demand for fertility, non-invasive or minimally invasive surgery has attracted increasing attention[5]. Currently, conservative treatment combining a local injection of methotrexate (MTX) or potassium chloride, oral mifepristone, and hysteroscopy is commonly used for cervical pregnancy with good efficacy[6-9]. However, high drug doses may induce damage to liver and renal function, as well as female fertility. In this context, it is challenging to develop a conservative treatment with a good safety profile[10].

Here, we report a typical case of cervical pregnancy treated by ultrasound-guided lauromacrogol injection combined with hysteroscopy. The effectiveness and safety were evaluated and the patient had a good outcome.

CASE PRESENTATlON

Chief complaints

The patient was 23 years old. She previously had five pregnancies and five abortions, including one ectopic pregnancy. She had menopause for 39 d and a little irregular vaginal bleeding for 10 d, and the last menstruation was recorded on January 23, 2020. She visited our hospital on March 2, 2020 due to similar symptoms. Her serum beta progesterone (P) was 17.06 ng/mL, and beta human chorionic gonadotropin (β-HCG) was 5077.0 IU/L. The patient was diagnosed with cervical pregnancy by transvaginal ultrasound (Figure 1) and was hospitalized.

History of present illness

The patient had menopause for 39 d and a little irregular vaginal bleeding for 10 d, and the last menstruation was recorded on January 23, 2020.

History of past illness

The patient had five intrauterine pregnancies including one tubal ectopic pregnancy, but no delivery.

Cervical pregnancy is mainly composed of fibrous connective tissue. It can cause compromised cervical contractions and a high risk of extensive bleeding[11]. If inappropriately managed, the outcome can be catastrophic. Conventional treatment mainly includes hysterectomy. With improvements in clinical diagnostic techniques and an increasing demand for fertility, non-invasive or minimally invasive surgery is preferred by both doctors and families. Therefore, the hysterectomy rate significantly decreased from 89.5% in 1979 to 21.7% in 1994[12]. Conservative treatments mainly include MTX +curettage + interventional embolization + mifepristone or potassium chloride, local injection of vasoconstrictor, ligation of the uterus, blood vessels, and internal iliac artery, cervical cerclage, cervical Foley tube tamponade, electrosurgical excision, and radiofrequency ablation[10,13-15]. However, the safety of conservative treatment has been less studied. MTX and mifepristone are commonly used drugs with definite efficacy in the treatment of cervical pregnancy. However, in the context of a high dose, patients can develop nausea, vomiting, or impaired liver and renal function, in addition to unpredictable fertility. It was reported that a minimum 3 mo interval after MTX application is required for a subsequent pregnancy[16].

Personal and family history

There was no abnormality in personal and family history.

Physical examination

At 15:09 on March 4, aborting under hysteroscopic visualization was performed under general anesthesia with intubation. A villous tissue block (approximately 1 cm x 1.5 cm) was present and removed (around 8 g) after intramuscular injection of 3 U of pitavastatin and 1 wk with a suction tube.Further hysteroscopy revealed a rough cervical canal with a little bleeding, and balloon compression for hemostasis was provided. The procedure was uneventful and the intraoperative blood loss was approximately 50 mL. On March 5, no abnormalities were observed on B-ultrasound (Figure 3A). β-HCG was 2049.0 IU/L on March 6, 1213.0 IU/L on March 7, 496.6 IU/L on March 9, and 0.68 IU/L on March 17.No abnormalities were detected in the uterine cavity on transvaginal ultrasound on March 6, and postoperative pathologic examination on March 17 showed the presence of villi and changes in the endometrium in the secretory phase (Figure 3B).

（2）地方法規方面：截至2017年三季度末，上海、河北、湖北和浙江四省市率先通過了地方綜合性信用法規相關立法條例，分別為《上海市社會信用條例》《河北省社會信用信息條例》《湖北省社會信用信息管理條例》和《浙江省公共信用信息管理條例》。在內容安排上，四部法規均涉及信用信息的歸集、披露、應用（激勵與懲戒/約束）、主體權益保障等共性內容。其中《上海市社會信用條例》對規范促進信用服務發展和信用環境建設進行了專章的介紹。

3.2 掩蓋藥物的不良氣味 大部分藥物均具有苦味和不良嗅味，隨著時代的發展，人們對藥物口味的要求越來越高。吉明霞[22]利用單凝聚法將藥物替米考星與明膠制成微囊進行苦味測定，結果發現微囊掩蓋苦味效果良好。楊抒等[23]對乳清蛋白酶解物進行微囊化處理，其苦味下降為原來的1/8，有效改善了苦味。微膠囊化可掩飾藥物本身的刺激氣味，而姜黃素具有苦味和辛辣味，將其包裹于囊中，可以掩蓋不良氣味，提高患者的順應性，便于服用。

Laboratory examinations

Serum beta progesterone was 17.06 ng/mL, and β-HCG was 5077.0 IU/L.

Imaging examinations

當海歸新生代企業接班人在融入中國情境后，便需要了解天時地利人和的理念。天時地利便是需要海歸新生代企業接班人了解企業的外部環境與企業現實基礎，這便是將時機與企業的生命周期結合；對待員工以人為本、善待競爭對手，是符合人和的觀念。

總會有一位旅客，在由長安出發之前，已由舊雨故交里打聽到了去萬花谷的路，會主動站出來，帶領大家離開黃梁驛，走向月光照耀的迷宮一樣的山嶺，發現那個草木交纏的洞口。雖然口口聲聲說不知道什么萬花谷，但老板娘心里一定也是像吞了螢火蟲似的，知道去萬花谷的溝溝坎坎，也許就是下一刻，她就會由墻壁上取下氣死風燈，提在手里，溫柔地一笑，對這三四十個長安客說：“你們已將十兩一盤的驢肉吃完了吧，現在跟我來，今晚我們不住黃梁驛，萬花谷的床鋪更溫暖！”

FlNAL DlAGNOSlS

The patient was diagnosed with cervical pregnancy.

1.盈利水平與研發支出資本化強度呈負相關關系。企業盈利水平越高，為減少可能承擔的社會責任，往往不會將研發支出資本化；而那些盈利水平較低的企業，為了提高企業價值，吸引更多投資，則更趨向于將研發費用資本化。

TREATMENT

Physical examination showed that the patient’s blood pressure was 122/83 mmHg, pulse rate was 89 bpm, temperature was 37.4℃, and respiratory rate was 20 breaths/min. Obstetrical examination findings included non-vaginal delivery, smooth vagina, slight bleeding, smooth and full cervix with no pain when held, severe uterine anteversion without tenderness, and normal bilateral fallopian tubes and ovaries.

In addition, there were no significant differences between baseline and 1-wk postoperative data with regard to serum indices including liver function, renal function, and routine blood analysis (Table 1).

從表1看出，黃土高原各生態區植被覆蓋度多年平均變化最小的是祁連山森林與高寒草甸草原生態區(Ⅲ-1)，最大的是黃土高原農業與草原生態區(Ⅰ -12)。從圖4看出， Ⅰ-12的植被覆蓋變化幅度最大，2001-2007年為第1階段緩慢上升，且變浮不大，在2007-2011年上升幅度較前一階段有所加大，而2011-2013年植被覆蓋上升到最大值0.595，2013-2014年開始下降； Ⅲ-1的植被覆蓋則一直較平穩，從2001年到2007年緩慢上升，2007年到2011年出現波動，有增有減。2011-2014年則幾乎持平，變化不大。

During the follow-up period, the patient had normal menstruation on April 12, with a normal volume and color, which finished within 5 d (Table 2).

The present case demonstrated the effectiveness and safety of lauromacrogol injection plus hysteroscopy in the treatment of cervical pregnancy, which had no adverse effects on liver and renal function,fertility, and fetal development following subsequent conception. This treatment strategy deserves to be promoted and applied in the clinic. Lauromacrogol, a sclerosant used to treat cystic disease or vascular disease, has certain adverse reactions, such as low-grade fever, local pain, venous embolism, and anaphylactic reaction, most of which are mild and self-limited. However, there is a risk of serious adverse reactions during the treatment of venous disease, and the occurrence of adverse heart events should be prevented[25]. Further research on clinical indications, contraindications, and its potential as a replacement for conventional hemostatic agents and blasticidin is necessary.

B-ultrasound was scheduled for the following day, and a gestational sac (approximately 22 mm x 13 mm) was situated in the cervical canal with a yolk sac and blood flow signals inside. In the meantime transvaginal ultrasound-guided tunnel puncture was thus arranged after routine disinfection using a 21G-EV type needle. Approximately 2 mL of fluid was obtained from the mass. Multiple lauromacrogol injections (3 mL) were performed targeting the cystic wall and cavity (Figure 2A). No pain or bleeding at the puncture area was observed during and after treatment. The patient was then transferred to the ward. Postoperative uterine three-dimensional B-ultrasound revealed the absence of blood flow signals around the gestational sac (Figure 2B).

OUTCOME AND FOLLOW-UP

Reproductive hormones, antral follicle count, and the endometrium all recovered to normal values, and no impairment of liver and renal function was observed after treatment. These findings indicate that lauromacrogol injection combined with hysteroscopy is effective and safe in the treatment of cervical pregnancy, and does not have adverse effects on fertility. Gestational and postnatal examinations showed subsequent normal fetal development. Thus, no short-term adverse effects were observed following this treatment strategy and subsequent pregnancy can be expected.

DlSCUSSlON

自2016年中國石化推出“公眾開放日”大型品牌活動以來，目前累計邀請社區居民、學生、媒體代表、政府官員等近10萬人次入廠參觀，展示了中國石化創新、綠色、開放的良好企業形象，成為央企首個品牌化公眾開放日活動，以及我國企業中最大規模的公眾開放日活動。

Lauromacrogol is a novel vascular sclerosant harboring hydrophilic and lyophilic groups, which conform to a directional alignment on a liquid surface to allow a significant decline in surface tension. It is important in sclerotherapy, as it can cause sterile inflammation with the groups which can help obtain protein precipitation in several seconds and thus cause damage to the lipid bilayer of the cell membrane, thereby leading to fibrous tissue hyperplasia and adhesions[17,18]. In addition, it has great applications in digestive, cardiovascular, and nervous system diseases[19,20]. However, there is a paucity of reports on lauromacrogol as a hemostatic agent in ectopic pregnancy. Wei[21] previously adopted ultrasound-guided local lauromacrogol injection plus suction curettage in the treatment of type II cesarean scar pregnancy with a favorable therapeutic outcome, but the safety of lauromacrogol was not evaluated.

Our patient had five intrauterine pregnancies including one tubal ectopic pregnancy, but no delivery.Considering the strong will of the patient and her family for fertility preservation, an attempt was made to decrease the blood supply in the gestational sac using local injections of lauromacrogol, instead of uterine artery embolization, combined with ultrasound-guided intervention. It has been established that lauromacrogol can block the blood circulation of the embryo and cervical vein without interfering with the blood supply to the ovary. The sclerosis and hemostasis induced by lauromacrogol are mainly realized in the following two ways: Vascular lauromacrogol injection can cause direct damage to vascular endothelial cells in attached veins at the site of injection, allowing local thrombosis, the formation of a protective layer for fibrous tissue surrounding the ruptured vessels, and an increase in vascular resistance. In that way, hemostasis can be obtained by regional vascular compression contributing to decreased blood flow. In addition, lauromacrogol injection can cause superficial small areas of fibrosis in veins around the injection site, resulting in vascular compression and occlusion[22].Here, B-ultrasound 24 h after lauromacrogol injection showed no blood supply to the gestational sac.Hysteroscopic curettage was instantly performed with a little intraoperative bleeding. This suggested the favorable vascular stiffening and rapid onset of action (3-24 h) of lauromacrogol, which greatly decreased intraoperative bleeding, shortened the time to curettage, and increased the success rate[23].Lauromacrogol is also a type of local anesthetic that can achieve local analgesia and alleviate discomfort in patients during treatment. Polycinol injection combined with uterine curettage under ultrasound intervention for cesarean scar pregnancy has no significant effect on endometrial thickness and scar thickness in patients. After the operation, the blood supply to the uterine scar recovers well, and the menstrual recovery time is significantly shorter than that following MTX treatment. In addition, the fertility of patients can be well preserved

Liver and renal function in our patient were also evaluated and showed no difference before and after treatment. Consistent with the existing literature, lauromacrogol had no adverse effects on the liver and kidneys. Similar results were observed for reproductive hormones, ovarian volume, antral follicle count,and the endometrium, resulting in a well preserved uterus and ovarian physiological functions. The patient had normal menstruation 40 d after treatment. She conceived naturally after 2 mo with normal fetal development (Figure 4) and successful delivery.

CONCLUSlON

There were 5-7 antral follicles in the left ovary and 6-8 follicles in the right ovary. The endometrium was 11 mm thick on the 15th day of menstruation. On September 18, 2020 (day 79 of subsequent pregnancy), nuchal translucency examination suggested normal fetal development (Figure 4). No abnormalities were observed on routine screening during pregnancy. A live healthy infant was delivered on April 8, 2021.

FOOTNOTES

Ye YJ and Gao Y wrote the introduction and discussion sections; Ye YJ and Ye JP performed the review of the literature and wrote the case report; Ye YJ and Lu LW revised the manuscript.

The patient agreed to the publication of this report and provided informed consent.

The authors declare no conflicts of interest for this article.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

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Jian-Pei Ye 0000-0003-0675-3751; Yang Gao 0000-0002-9177-7872; Li-Wei Lu 0000-0002-1218-3647;Yong-Ju Ye 0000-0002-7269-3251.

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