Early pregnancy loss is a common event in the first trimester of pregnancy, occurring in 10%–20% of confirmed pregnancies [1, 2, 3]. Approximately 50%–60% of all cases of early pregnancy loss are associated with fetal chromosomal abnormalities [1, 4, 5, 6]. However, the common risk factors identified among women who have experienced early pregnancy loss are advanced maternal age and prior early pregnancy loss [1, 6]. Other maternal etiologies include antiphospholipid syndrome, assessment of uterine anatomy, hormonal and metabolic factors, and lifestyle variables [7, 8, 9, 10, 11].

Intrauterine adhesion (IUA) is a condition characterized by the formation of bands of fibrous tissue within the uterine cavity, which partially or completely replace the endometrial lining. This occurs due to injury to the basal layer of the endometrium [12, 13, 14]. Hysteroscopy is a precise diagnostic method for identifying IUA [15]. Based on hysteroscopic assessment, IUA can be classified into different types such as isthmic, marginal, central, or severe [16]. While approximately one in five women encounter IUA after early pregnancy loss terminated by uterine aspiration [17, 18, 19], the prevalence of IUA in patients terminated by medical treatment is rarely reported. In turn, endometrial scarring can hinder embryo implantation or halt its development [20]. Given the acceptance of reproductive freedom, IUA resulting from early pregnancy loss should not be overlooked. How to reduce the incidence of early pregnancy loss is the common goal of clinicians.

This study aimed to explore the risk factors of early pregnancy loss by comparing with early termination of pregnancy. In this study, hysteroscopy was innovatively used to diagnose IUA during abortion, so IUA is analyzed as a possible risk factor, which perhaps further provide help for the prevention and treatment of early pregnancy loss.

From March 2020 to February 2021, we assessed 226 early pregnancy loss participants and 51 early pregnancy participants for eligibility (Table 1). All cases had completed the process without perforation, infection, or other complications. There were 8 cases of early pregnancy loss and 5 cases of early pregnancy underwent emergency uterine aspiration followed by hysteroscopy due to massive bleeding and incomplete expulsion after 6 hours of treatment with medicine. 264 participants had been observed 6 hours after management with medicine and were then examined by hysteroscopy. Complete expulsion occurred in 93 of 226 women (41.15%) in early pregnancy loss cases, and in 5 of 51 women (9.8%) in early pregnancy cases (Fig. 1).

Fig. 1.

Enrollment and Analysis.

Residual gestational tissue and shape of the uterine cavity were evaluated by hysteroscopy. If complete expulsion occurred, there was no sac in the uterine cavity (Fig. 2A); instead, the sac was still in the uterine cavity (Fig. 2B), in which event uterine aspiration was performed under hysteroscopy. When the residual gestational tissue was removed, the shape of the uterine cavity could be visually evaluated as either normal (Fig. 2C), with a band of scar adhesion tissue found in the middle of the uterine cavity (central IUA) (Fig. 2D), or with scar adhesion tissue found on the wall of the uterine cavity (marginal IUA) (Fig. 2E). Extensive firm adhesions with agglutination of the uterine walls or in which at least one tuba ostium area was occluded were also diagnosed as IUA.

Fig. 2.

The shape of the uterine cavity under hysteroscopy after medicine management. (A) The gestational tissue was completely expelled, and the shape of the uterine cavity was normal. (B) The gestational tissue was not expelled. (C) The shape of the uterine cavity was normal after uterine aspiration. (D) Central intrauterine adhesion was found after uterine aspiration. (E) Marginal intrauterine adhesion was found after uterine aspiration. IUA, intrauterine adhesion; GS, gestational sac.

In our retrospective study, IUA, or Asherman’s syndrome, as an acquired uterine cavity abnormality, was a risk factor for early pregnancy loss, in line with the published literature [21, 22, 23]. IUA is a scar disease in fact, which will cause the embryo implantation failure, or the embryo stops developing. This may be the reason why IUA was positively associated with early pregnancy loss in this study. Hysteroscopy is the gold standard for the diagnosis of IUA [24, 25, 26]. In this study, hysteroscopy was used to confirm whether there was residual trophoblast tissue which could then be removed in time; moreover, it was effective in evaluating the shape of the uterine cavity after abortion, as typical adhesions can be observed and simultaneous adhesiolysis can be operated to prevent the aggravation of IUA. However, diagnosing IUA immediately might not be optimal due to the risk of missed diagnosis, as uterine involution might not be complete at this stage. Although all hysteroscopy operations in this study were performed by one senior physician to minimize bias, the actual prevalence of IUA might have been higher than our data suggest. Additionally, early pregnancy patients who needed hysteroscopy termination of pregnancy might have harbored concerns about IUA or insufficient medication efficacy, leading to potential selection bias in the study.

According to the guidelines for transvaginal ultrasonographic diagnosis of early pregnancy loss [1, 27], diagnosing early pregnancy loss can be challenging in the gestational weeks due to the requirement of waiting for more than two weeks. As the gestational week increases, the diagnosis of early pregnancy loss becomes easier and more definitive. This may be the reason why gestational weeks was positively associated with early pregnancy loss in this study. Hence, timely diagnosis of early pregnancy loss is often challenging. Maternal age was the risk factor for early pregnancy loss, in line with the published literature [1, 6]. Previous early pregnancy loss is considered a risk factor for subsequent occurrences, but this study did not find it to be a significant factor [1, 6]. This may be due to sample size limitations.

In clinic, for those patients with risk factors for early pregnancy loss, follow-up and monitoring should be emphasized to facilitate early diagnosis and treatment. For patients experiencing early pregnancy loss and presenting risk factors for IUA, such as a history of recurrent miscarriages, multiple dilation and curettage procedures, multiple pregnancies, or issues like retained products of conception and placenta implantation, it is necessary to consider uterine aspiration under hysteroscopy or hysteroscopy following treatment with medication [28, 29, 30]. The goal is to prevent missed diagnosis of IUA and subsequent early pregnancy losses from the same cause.

Early pregnancy loss is a common event in the first trimester of pregnancy. The common risk factors identified among women who have experienced early pregnancy loss are advanced maternal age and prior early pregnancy loss. According to this study, we found that maternal age, gestational weeks and, IUA were risk factors associated with early pregnancy loss. Approximately one in five women encounter IUA after early pregnancy loss terminated by uterine aspiration. In turn, endometrial scarring can hinder embryo implantation or halt its development. IUA resulting from early pregnancy loss should not be overlooked. Combined IUA should be vigilant when managing early pregnancy loss.

Data and other materials can be made available by the corresponding author upon a reasonable request.

CC and XL contributed equally to this work. CC, QZ, XL and ZH contributed to the study concept and design; CC completed Hysteroscopy; CC, XY and YC contributed to the acquisition of the data; BP, YC analyzed and interpreted the data; QZ, CC, XL and XY drafted the manuscript; QZ, CC, BP, YC provided critical revision of the manuscript; QZ, XL and ZH supervised the study. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the first affiliated Hospital of Chongqing Medical University (approval number 058/2020). Informed consent was obtained from all participants.

We greatly appreciate the support from the colleagues in Department of Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University.

This research received no external funding.

The authors declare no conflict of interest.