Decidualization of ovarian endometriomas in pregnancy is not rare. In our prospective study, this phenomenon occurred in seven out of 45 endometriomas, corresponding to 16% (95%CI: 8–29%). In addition, our study confirms previous findings suggesting that decidualization of ovarian cysts essentially develops during the first trimester of pregnancy, remains steady or regress during the second trimester of pregnancy and consistently disappears after delivery.1,2,7
Three previous retrospective studies reported on the incidence of endometriomas’ decidualization. Our results are in line with the rates reported by Ueda et al.,6 and Pateman et al.7, but higher that what reported by Bailleux et al..8 Combining all these three reports with our findings (in total 15 decidualizations out of 151 endometriomas) allows to estimate that the frequency of decidualization would be about 10% (95%CI: 6–16%), i.e. one out of 10 cases.
The awareness that endometrioma decidualization is relatively common should be kept in mind when vascularized projections suddenly develop at the beginning of pregnancy in women knowing to carry ovarian endometriomas. Decidualization rather than cancer degeneration is by far the most plausible explanation in these cases and women should be reassured. However, this element may be less valid in natural compared to IVF pregnancies because women who conceive spontaneously are not always aware of carrying an endometrioma. In these cases, an in-depth sonographic evaluation in referral centers is needed to minimize misdiagnoses.
The natural history of DIE nodules in pregnancy partly differed from ovarian endometriomas. Firstly, in four cases, we were unable to identify the lesions. The short time interval between the basal and first assessment that was done at 6–7 weeks’ gestation tends to rule out the possibility of resorption of the lesions. We initially interpreted this evidence as a consequence of a modification of the echogenicity, a change that can impair the capacity to distinguish them from the surrounding organs. However, this explanation contrasts with the observation that lesions could not be detected in three cases after delivery. A false positive diagnosis at basal ultrasound is an alternative explanation that we cannot exclude.13 Secondly, we observed a significant growth of the lesions and an enhanced vascularization in a consistent proportion of DIE cases. Even if our statistical power is insufficient for robust conclusions, the frequency of these changes appears more frequent than for endometriomas. Thirdly, these modifications tend to progress over pregnancy rather than self-limiting at the end of the first trimester, as observed for endometriomas. Interestingly, Coccia et al. studied three women with DIE during pregnancy and also reported a progressive growth of the nodules up to 24 weeks’ gestation, but then a progressive regression.9 No data was reported on vascularization. Based on our findings, we suggest to define DIE decidualization as an increase in mean diameter of the nodules of more than 50% associated with an increase of color score. To note, as in general blood flow cannot be found in DIE lesions (color score = 1), this latter criterion could be changed into detection of a color score ≥ 2. Admittedly, this definition of DIE decidualization is arbitrary. A more valid definition would be based on clinical consequences, i.e., the definitions of changes that are associated with increased risk of pregnancy complications.14–16
Decidualization of endometriosis in pregnancy is enigmatic and intriguing. Why do most changes occur in the first trimester? Why does decidualization occur in some but not all lesions? Our study cannot address these important queries. Nonetheless, the observation that in a woman with bilateral endometriomas decidualization was observed in only one cyst suggests that this event is lesion- rather than patient-specific. Similarly, even if our definition of DIE decidualization needs confirmation, we observed women who had DIE but not endometrioma decidualization and the other way round. One may speculate that this could depend on the relative component of endometrial cells and fibrosis within the lesions.17 Possibly, decidualization could occur also in cases with higher fibrotic component but being so limited it is undetectable at ultrasound. Another possibility is that endometriotic cells of different lesions may differently respond to pregnancy hormones. One may speculate that older lesions could be less sensitive. Biological evidence to support these pathogenic hypotheses is however lacking.
Some limitations of our study deserve to be commented. Firstly, we lack the histological confirmation of the diagnosis of decidualization, as none of the included patients underwent surgery for endometriosis during the follow-up. We also lack histological confirmation of endometriosis. However, this second limitation is of doubtful relevance given the elevated accuracy of transvaginal ultrasound, in particular in experienced hands.18 Secondly, reliability of ultrasounds to monitor ovarian lesions during pregnancy is not validated. This limitation is particularly relevant for the assessments performed in the second part of pregnancy because of the presence of the enlarged uterus that can hide the lesions or complicate their visualization. In fact, the transabdominal approach was commonly required in advanced pregnancy. Thirdly, all the included pregnancies were achieved with IVF. This gave us the possibility to have an ultrasound evaluation just before pregnancy, thus providing accurate evaluations. However, caution is warranted prior to generalize our conclusions to the whole population of women with endometriotic lesions. We cannot exclude a synergistic effect of ovarian hyper-stimulation (and thus the presence of multiple corpora lutea) and pregnancy. There is some biological evidence supporting this possibility.19,20 To note, in our series, all the decidualized endometriomas were observed among women who had fresh embryo transfer (thus being exposed to ovarian hyperstimulation) and none among those achieving pregnancy with frozen embryos. However, this difference was not statistically significant.
In conclusion, decidualization of ovarian endometriomas in pregnancy is common. A correct diagnosis is essential to avoid useless and possibly harmful surgery. In addition, our study shows that also DIE nodules can undergo important modifications during pregnancy that can be detected at ultrasounds, in particular the increase in vascularisation. Further evidence is needed to clarify the possible additive effect of ovarian hyper-stimulation and to draw a shared definition of DIE decidualization.