Studies have demonstrated that the endometrium of women with endometriosis is different to that of women without endometriosis (1,2). Those differences may interfere with normal implantation as well as placental growth (3). However, the existing literature has demonstrated conflicting results regarding a possible link between endometriosis and miscarriage. Let us have a look at the evidence.

 It is worth remembering that the majority of studies that examined this topic relate to woman that conceived via artificial reproductive technology (ART) methods and this makes accurate interpretation of results more challenging (4,5). In a retrospective study of 108 women that had undergone laparoscopic management of endometriosis, the risk of spontaneous miscarriage was not significantly higher, compared to women without endometriosis (6). A study of 274 patients failed to demonstrate such a link (7), and the same happened in a study of 330 patients with endometriosis (8). In a retrospective study by Santulli et al. (9), 284 patients with a histological diagnosis of endometriosis were found to have a higher risk of miscarriage, compared to women without endometriosis. The stage of endometriosis does not appear to be associated with the risk of miscarriage, while pregnancy losses were more common in patients with superficial endometriosis (SUP) (albeit, that the risk is higher for all 3 phenotypes of endometriosis, compared to women with no endometriosis). Of particular interest is a recent (2023) Danish large population study of nearly 30.000 women with endometriosis which demonstrated that the disease is associated with a higher risk of miscarriage, as well as recurrent miscarriages, and the link appears to be stronger as the number of miscarriages rises (10).

  Let us, now, have a look at the evidence coming from the systematic reviews and meta-analyses of the existing literature: Zullo et al. performed a comprehensive review of 24 studies and demonstrated that, amongst other pregnancy- related complications, endometriosis is associated with a higher risk of miscarriage (11). Minebois et al. only included 4 original studies of 31.167 women with endometriosis and spontaneous conception: they concluded that endometriosis significantly increases the risk of miscarriage, as much as by 80% (12). In a systematic review by Maggiore et al. that included both cases of spontaneous conception as well as conception via ART, endometriosis did not appear to increase the risk of miscarriage (13). Huang et al. demonstrated that endometriosis increases the risk of miscarriage in those women that has conceived spontaneously, however, in those women that had conceived following ART, the risk was similar to those with ‘’tubal factor’’ infertility (14). They also found that the risk of miscarriage does not increase with ‘’more advanced’’ (higher stage) endometriosis. When they looked at the 3 different phenotypes of the disease, they found that endometrioma (chocolate cyst of the ovary, OMA) was not associated with a higher risk of miscarriage, in contrast to deep endometriosis (DE) as well as Superficial Peritoneal Endometriosis (SUP). 2 systematic reviews that examined the effect of endometriosis on the risk of miscarriage in women that had strictly conceived following ART methods, provided us with conflicting results. Barbosa et al. found a small to moderate increase in the risk (15), whilst Hamdan et al. did not demonstrate an increased risk (16).

  Through which mechanisms, though, can endometriosis increase the risk of pregnancy loss? Other than the aforementioned changes in the endometrium, the disease is linked with increased levels of inflammatory factors and oxidative stress that has a negative effect on the oocyte and embryo quality (17). What is more, inflammatory factors may also be the cause of the increased miscarriage risk. (10).

  As regards the management methods of endometriosis and their effect on the miscarriage risk in women with endometriosis, older randomized controlled trials (RCTs) failed to demonstrate a protective effect of surgery (18,19). However, those result should be interpreted with caution, due to the small number of patients. What is more, their conclusions are in contrast with the findings of Groll’s study (20), which demonstrated a protective effect of surgery as well as medical management of endometriosis with danazol. Moreover, a 6-month regime of GnRH agonists pre- IVF appears to reduce the risk of miscarriage in women with endometriosis (21).

    In conclusion, although it has not yet been clearly demonstrated that endometriosis increases the risk of miscarriage, such a link appears likely based on existing literature. A recent study demonstrated that endometriosis appears to increase the risk of recurrent miscarriages as well, and the link appears to be stronger with increasing number of pregnancy losses. The risk does not appear to be higher in more advanced stages of the disease, while it is not clear that any of the three phenotypes is linked with a higher risk of miscarriage. Further, well-designed studies are need to shed light on the link between endometriosis and miscarriage.

References :

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