The body mass index and the risk of ectopic pregnancy: a 5-year retrospective case-control study

In this study, we directly included risk factors associated with ectopic pregnancy as well as body mass index to conduct univariate and multivariate analysis. This is a relatively systematic study of risk factors for ectopic pregnancy, a new variable of body mass index was also included. We found the history of ectopic pregnancy, history of induced abortion, age > 35 years old and low BMI (< 18.5 kg/m²) were the risk factors with EP. And low BMI (< 18.5 kg/m²) was 1.929 times higher risk to EP compared with normal BMI (18.5 kg/m² ~ 24.9 kg/m²). Our findings hope that it may improve awareness of these factors, and further research common to these conditions.

Theoretically, any condition that prevents or retards migration of the fertilized ovum to the uterus could predispose a woman to ectopic gestation (current intrauterine device use, the history of infertility, the history of pelvic inflammatory disease, and prior tubal surgery) [18]. As the economy develops, more and more women choose the contraceptive method of IUD. The risk of ectopic pregnancy in different types of intrauterine device may be different, and the concentration of drugs in IUDs may have some mechanism of action with fallopian tube function. In addition, IUDs are foreign to the uterine cavity and may cause the endometrium to be out of sync with fallopian tube function [19, 20]. Pelvic inflammatory disease (PID) changes the inner environment of the pelvic uterus, affecting the transport environment of fallopian tubes, thereby increasing the risk of ectopic pregnancy. The two most common pathogens, Neisseria gonorrhoea and chlamydia trachomatis, have been shown to be mainly associated with ectopic pregnancy [21‐23]. Whether the inflammation caused by appendicitis also affects the function of fallopian tubes, there is currently no evidence of higher levels. However, some retrospective studies have shown that the history of appendectomy is associated with increasing risk of ectopic pregnancy [24]. In contrast to our study, we found that women with previous history of appendectomy were not at increased risk of ectopic pregnancy, either through univariate analysis or and multivariate analysis. So, the problem is whether abdominal surgery or inflammation of the appendix caused the ectopic pregnancy. Similarly, the history of two or three cesarean deliveries is associated with increased risk for subsequent ectopic pregnancy in relation to women who had one prior cesarean delivery [25]. We hypothesize that multiple prior cesareans may increase pelvic adhesion leading to tubal hypoplasia. However, there is no experimental evidence.

With age, some risk factors associated with ectopic pregnancy may accumulate. Epidemiological surveys showed a worldwide phenomenon of postponement of the age of childbearing to the 30s, fertility rates were also declining [26]. With the improvement of economic and educational level, the divorce rate and multiple sexual partners among these women are likely to increase [27]. This may lead to pelvic inflammatory disease and tubal disease, and ectopic pregnancy. In a Chinese study, the proportion of EP among those ≥ 35 years old was reversed from a downward trend (2011–2016 annual percentage change (APC) − 4.13) to an upward trend (2016–2020 APC 4.04) [28]. Some study showed that age > 35 years increased the risk of ectopic pregnancy [29, 30]. In agreement with our data, ectopic pregnancy was more likely to occur over the age of 35, the value of odds ratio was 5.415 and the largest in this study, there was a major impact effect on ectopic pregnancy.

There has been a great deal of research showing that an increased risk of repeat EP in patients with history of ectopic pregnancies. In a large French case-control study, women with one ectopic pregnancy had the higher risk of repeated ectopic pregnancy (OR = 12.5), especially for women with two or more ectopic pregnancies [9]. In a recent study, women with the history of ectopic pregnancy had the 2.72 times higher risk of ectopic pregnancy recurrence (Adjusted odds ratio [AOR] = 2.72, 95% confidence interval [CI]: 1.83–4.05) [19]. In our study, multivariate analysis showed that the risk of ectopic pregnancy was 3.944 times higher in women with the history of ectopic pregnancy. Women with previous history of ectopic pregnancy may affect fallopian tube function after conservative or surgical treatment, such as oviduct blockage, oviduct water accumulation, oviduct inflammation, etc.

Induced abortion remains noticeable in China [31]. In a recent cross-sectional study, of all abortions, 65.2% were repeat induced abortions [32]. The history of induced abortion was associated with an increased risk of ectopic pregnancy [OR, 1.5; 95%CI, 1.0 ~ 2.0], particularly in the case of women who have had several induced abortions [33]. In a prospective study by Skjeldestad, Induced abortion did not increase the risk of ectopic pregnancy [34]. In our study, the history of induced abortion was significantly associated with ectopic pregnancy(OR, 3.365; 95%CI, 2.724 ~ 4.158). But the relationship between history of spontaneous abortion and ectopic pregnancy was no statistically significant. We assumed that one or more abortions increased the chance of uterine manipulation, leading to an enhanced risk of uterine infection. The possibility of pelvic inflammatory disease and tubal disease cannot be excluded.

In this study, we considered the inclusion of body mass index to explore the risk factors for ectopic pregnancy. However, the relationship between BMI and EP is rarely studied. Pan pointed out that obese women have a higher risk of EP [16], and it was suggested that low BMI was associated with EP after receiving ART in this prospective study [15]. In these studies, the relationship between BMI and EP was not directly investigated, and other factors associated with EP were not controlled. Therefore, there was difference. In our study, by including risk factors associated with EP, multivariate analysis showed that body mass index was associated with EP after adjustment and appeared in low BMI (< 18.5 kg/m²). There were few reports in the literature on the mechanism. We consider that leptin levels in women with low body mass index are alternately regulated with insulin growth factor-1 [35, 36], and that leptin is critically linked to reproductive function [37]. However, a unique hormonal regulation exists during embryonic development, maturation, and egg transport through the fallopian oviduct [38]. This suggests that it may affect embryonic development and fallopian tube function by impacting hormonal regulation.

This study is a retrospective study, which effect is less than randomized controlled studies. Subsequent multicenter trial and large-sample research is required. The BMI is a new risk factor compared to other factors, which is a highlight of our research. We are better able to regulate weight relative to other physiological factors to guide the clinical.