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Abstract
Aim To assess whether adverse pregnancy outcomes in women with adenomyosis are different according to the method of conception and the concurrent of uterine leiomyoma (UL).
Methods We performed a retrospective study. Fifty-three singleton pregnancy cases complicated with adenomyosis were included in this study. In the study group, 15 women became pregnant with assisted reproductive technology (ART) and 21 women combined with UL. Pregnancy outcomes were compared between ART and non-ART, UL and non-UL groups.
Results The prevalence for such complications as hypertensive disorder complicating pregnancy (HDCP)and postpartum hemorrhage (PPH)were significantly higher in the women conceived by ART (33.3% vs. 5.3%, P = 0.023) and (53.3% vs. 23.7%, P = 0.037),respectively. And women concurrent with UL of which the diameter≥4 cm were more likely to have severe PPH (44.4% vs. 0%, P = 0.021).
Conclusion ART may increase the risk of adverse pregnancy outcomes such as HDCP and PPH in women with adenomyosis and UL of which the diameter≥4 cm may further increase the risk of severe PPH.
Highlights
Women conceived with adenomyosis were of higher age, BMI, ART ratio, and higher rate of concurrent UL.
Women with adenomyosis have a higher risk of many adverse pregnancy outcomes.
ART may further increase the risk of hypertensive disorder and PPH.
Uterine leiomyoma of which the diameter≥4 cm may increase the risk of severe PPH.
- Adenomyosis
- Adverse pregnancy outcomes
- Assisted reproductive technology
- Uterine leiomyoma
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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1 Introduction
Adenomyosis refers to a pathologic condition in which the ectopic endometrial glands and stroma invade the myometrium, leading to dysmenorrhea, dyspareunia, subfertility, etc.1 Among infertile women, the prevalence of adenomyosis is reported to range from 10% to 90%.2,3 In recent years, the number of pregnant women with adenomyosis has increased with the trend of delayed pregnancy and the development of ART.4 For women with adenomyosis who have completed childbirth, removal of the uterus is the most reliable treatment while the treatment strategies for adenomyosis patients with fertility requirements have always been difficult problems faced by gynecologists.
Most previous studies have focused on exploring the negative impact of adenomyosis on the results of ART,5,6 while are relatively few studies exploring the effect of concurrent UL or ART on pregnancy outcomes in women with adenomyosis. Razavi M et al.7 reviewed the impact of adenomyosis on pregnancy outcomes in a recent meta-analysis and found that the prevalence of premature delivery, preterm premature rupture of membranes (PPROM), spontaneous abortion, gestational diabetes mellitus (GDM), pre-eclampsia and small for gestational age (SGA) increased significantly in pregnant woman with adenomyosis. Previous studies have shown that ART will also increase the prevalence of adverse pregnancy outcomes to a certain extent.8,9 Pregnancies achieved via ART are confounded by several obstetric complications, including HDCP and placental malposition. Shin YJ et al.10 detected the risk of preterm births in pregnant women with adenomyosis and demonstrated that the increased risk of premature birth and low birth weight (LBW) infants was related to those women who conceived by ART but not in women who conceived spontaneously.
Approximately 6%–20% of patients with adenomyosis have concurrent endometriosis, and approximately half of patients have concurrent UL.11 In the past decades, a large number of studies have reported that endometriosis is associated with various adverse pregnancy outcomes.12,13 In our previous research, we detected that endometriosis significantly increases the risk of PPH and women with endometriosis have an upward tendency of developing other adverse pregnancy outcomes, such as preterm birth, placental abruption, placenta previa, cesarean section, fetal distress and anemia.14 Scala C et al.15 recently explored the impact of adenomyosis on pregnancy outcomes in women with endometriosis, and concluded that the presence of adenomyosis in women with endometriosis significantly increases the risk of placental dysfunction and SGA. So we excluded pregnant women who also had endometriosis to investigate the impact of adenomyosis on adverse pregnancy outcomes.
Meanwhile, there was few research detected the risk of adverse pregnancy outcomes among pregnant women with adenomyosis concurrent UL. This study aimed to assess whether adverse pregnancy outcomes in women with adenomyosis are different according to the method of conception and the concurrent of UL.
2 Materials and methods
Data for the study were obtained from the database of women at the Department of Obstetrics and Gynecology, Peking University People's Hospital. We retrospectively analyzed medical records of singleton pregnant women diagnosed as having adenomyosis at our hospital during the period from January 2015 through December 2020. The diagnostic criteria for adenomyosis is ultrasonography (USG)16: (i)a. myometrial anterior posterior asymmetry; and/or b. thickening of the anterior and posterior myometrial walls, with either increased or decreased echogenicity), (ii) women who received routine prenatal checkups during the entire pregnancy and gave birth in the same hospital. The exclusion criteria were (i) women with endometriosis, previous uterine surgery, pregnancies with severe fetal structural abnormalities, known autoimmune diseases or fetal aneuploidy, and multiple pregnancy, (ii) women with malignancies, immune system diseases, endocrine diseases, cardiovascular diseases, and other complications. A total of fifty-three pregnant women who met the above diagnostic criteria and did not meet the exclusion criteria were included in the study.
3 Methods
We compared maternal characteristics and pregnancy outcomes according to mode of conception and concurrent uterine leiomyoma.
Adverse pregnancy outcomes included cesarean section rate, GDM, HDCP, PPROM, PPH, SGA, placenta previa, abortion and preterm birth. Neonatal outcomes included birth weight and gestational age at delivery. PPH, defined as vaginal bleeding ≥500 ml and cesarean bleeding ≥1000 ml within 24 h after delivery, which is not only a serious complication of delivery but also the primary cause of maternal death in China. Severe PPH is defined as bleeding volume ≥1000 ml within 24 h after delivery.
4 Statistical analysis
The data were calculated and analyzed by SPSS 22.0 software. Continuous variables conforming to the normal distribution are presented as mean ± standard deviation (SD) and compared by Student's t-test. For continuous variables that do not conform to the normal distribution, the median (interquartile range) is used for statistical description, and Mann-Whitney U test is used for comparison. Categorical variables were compared by Chi-square test or Fisher's exact test. We used to binary logistic regression to evaluate the association between exposure covariates and adverse pregnancy outcomes. P < 0.05 was considered statistically significant.
5 Results
In the study, 53 women conceived with adenomyosis as the study group were analyzed to investigate pregnancy outcomes. 15 women conceived by ART and 21 women combined with uterine leiomyoma.
As shown in Table 1, we compared the maternal characteristics and pregnancy outcomes according to the method of conception. The proportion of multipara (6.7%) in the ART group was significantly lower than that in the non-ART group (50%) (P = 0.009) and the prevalence of HDCP (33.3% vs. 5.3%, P = 0.023) and PPH (53.3% vs. 23.7%, P = 0.037) were significantly higher in the ART group than in the non-ART group.
Basic characteristics and prevalence of adverse pregnancy outcomes according to the method of conception.
Comparative data on pregnancy outcomes with concurrent UL are shown in Table 2. No statistically significant differences were found in maternal characteristics and pregnancy outcomes between the UL group and non-UL group. So we next conducted further research according to the size of UL and found that women with adenomyosis conceived with uterine leiomyoma of which the diameter is ≥ 4 cm was more likely to have severe PPH (44.4% vs. 0%, P = 0.021)(Table 3).
Comparison of maternal characteristics and prevalence of adverse pregnancy outcomes according to the size of uterine leiomyoma.
Comparison of maternal characteristics and prevalence of adverse pregnancy outcomes according to whether combined with uterine leiomyoma.
6 Discussion
Previous studies have shown a higher incidence of adverse pregnancy outcomes in women with adenomyosis after pregnancy.7 And we further analyze the above results according to the method of conception and concurrent UL and the results show that the incidence of HDCP and PPH were significantly higher in women with adenomyosis conceived by ART, and women with adenomyosis conceived with UL of which the diameter≥4 cm was more likely to have severe PPH.
Although adenomyosis and endometriosis share a number of similar characteristics, some researchers believe that they are two different diseases.17 Scala C et al.15 recently explored the effect of adenomyosis on pregnancy and perinatal outcomes in women with endometriosis, and concluded that compared with those with endometriosis only, patients with diffuse adenomyosis had significantly higher prevalence of SGA (40% vs 10.8%) while no statistically significant differences were found in patients with focal adenomyosis compared with those with endometriosis only. Logistic regression analysis demonstrated that diffuse adenomyosis was the only independent risk factor for SGA. In this study, we excluded pregnant women who also had endometriosis to investigate the impact of adenomyosis on adverse pregnancy outcomes. Regarding the pathogenesis involved in adverse pregnancy outcomes of adenomyosis, the role of inflammation, the production of prostaglandins in the myometrium, changes in uterine contractility, increased intrauterine pressure and impaired implantation can explain the association with premature delivery and PPROM.18–20 Regarding the increasing prevalence of placenta-related diseases such as the HDCP, fetal growth restriction etc., unbalanced perfusion of the placenta caused by the remodeling of myometrial spiral artery and vascular stealing are considered to be the main causes.21,22
Pregnancies achieved via ART are confounded by several obstetric complications, including HDCP and placental malposition.8,23 Shin YJ et al.10 demonstrated in a recently study that adenomyosis increases the risk of preterm birth and LBW, which is related to the mode of pregnancy, and seems to be more pronounced in pregnant women with ART. Vercellini P et al. concluded in a recent meta-analysis that adenomyosis has a negative impact on the outcome of ART, owing to reduced possibility of clinical pregnancy and implantation, and increased risk of early miscarriage.3 They suggested that screening for adenomyosis in infertile women entering an ART program is worthy and should be encouraged. In this study, we found that the proportion of multipara was significantly lower and the incidence of HDCP and PPH were significantly higher in the ART group than that in the non-ART group. However, due to the limitations of low sample size and retrospective studies, this conclusion still needs to be confirmed by future large-sample prospective cohort studies and randomized controlled studies.
Previous studies have found that in uterine specimens with adenomyosis, 6%–22% of patients also concomitant endometriosis, and 35%–55% of patients concomitant UL.11 The presence of myomas, especially myomas that distort the uterine cavity and larger intramural myomas, are associated with infertility. In terms of pregnancy outcome, it is associated with increased risks of spontaneous abortion, fetal malpresentation, placenta previa, premature delivery, cesarean section and PPH.24 No statistically significant differences were found in maternal characteristics and pregnancy outcomes between the women conceived with the UL or not in this study. Current evidence suggests that submucosal fibroids and intramural fibroids larger than 4 cm in diameter have an adverse effect on conception and early pregnancy, while subserosal fibroids seem to have no significant effect on reproduction.5 So we next conducted further research according to the size of UL and found that women with adenomyosis conceived with UL of which the diameter is greater than or equal to 4 cm was more likely to have severe PPH. The presence of submucosal and/or larger intramural fibroids is also associated with adverse pregnancy outcomes.5 Among the pregnant women with UL, only one had submucosal fibroids, and the rest were intramural fibroids in the present study. Multi-center studies are necessary to clarify the impact of concurrent UL and adenomyosis on adverse pregnancy outcomes in the future.
The presented study has some important limitations. Firstly, adenomyosis in this study was diagnosed by USG which was reported to have the sensitivity and specificity to be 36.8% and 91.8% in the previous study which undoubtedly increased the risk of selection bias.25,26 Secondly, it is a retrospective study with a small sample size conducted in a single center, which inevitably reduces the credibility of the conclusion, a larger prospective study is necessary in the future.
7 Conclusion
In women conceived with adenomyosis, ART may increase the risk of HDCP and PPH and UL of which the diameter≥4 cm may further increase the risk of severe PPH. These results are potentially useful for preconception and prenatal counseling of women with adenomyosis and especially those conceived by ART and with UL.
Author contributions
WYL and TZ contributed to study conception and drafted the article. ZHL directed the project, contributed to discussion, reviewed and edited the manuscript. CXH and CH contributed to manuscript editing and revision. ZHL as the corresponding author had full access to all the information in the study and had final responsibility for the decision to submit for publication.
Ethics approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Peking University People's Hospital Ethics Committee.
Consent to participate
This study is a retrospective study and informed consent had been waived by Ethics Committee of Peking University People's Hospital.
Declaration of competing interest
The authors declare that they have no conflicts of interest.
Acknowledgments
This work was supported by “Natural Science Foundation of Beijing Municipality” [No: 7222206].
References
Footnotes
↵1 These author contribute equally to this manuscript