The present study demonstrates that delivery by primary cesarean section showed a trend towards being more frequent in controls and being associated with conception by ART, while delivery by secondary cesarean section showed a trend towards being more frequent in endometriosis patients. Miscarriages occurred more frequently in controls. Deep infiltrating endometriosis was not associated with an increased risk of miscarriage, delivery by secondary cesarean section or obstetric complications when compared to other types of endometriosis. Adenomyosis and bladder endometriosis was associated with an increased risk of secondary cesarean section compared to other types of endometriosis. During pregnancy endometriosis was associated with increased risk of bleeding, early uterine contractions and cervical insufficiency and there was a trend towards more pre-eclampsia and amniorrhexis. During delivery endometriosis was associated with increased risk of bleeding, vaginal tear and symphysis pubis diastasis. During puerperium endometriosis was associated with increased risk of bleeding, infectious complications and complications in general. Complications were mainly Clavien Dindo I or II categories in case of endometriosis, while controls showed a trend towards higher risk of Clavien Dindo III complications. Clavien Dindo IV and V complications did not occur. When compared to control groups from the literature, which other than in this study’s controls represent the general population, patients from the study’s endometriosis group showed an increased risk of placenta praevia and placental abruption, as well as miscarriage and delivery by cesarean section.
Return rate for the questionnaire was good in the endometriosis group (51.5 %) and acceptable in the control group (31.9 %). Due to the chronicity of endometriosis many of the patients affected were treated at the University Hospital of Muenster for a long time, which may explain the higher return rate for women with endometriosis when compared to the control group as a result of higher compliance. Only cases of women with endometriosis diagnosed and classified by a specialist were included in the survey, which may be a strong point of this study. The answers given by the patients however could not always be verified by analysing original medical documents. Especially symptoms like pain, nausea and even light bleeding might be underreported as these were considered to be common symptoms in pregnancies and therefore not noteworthy.
As in Sharma et al [17] pregnancy rate was similar in patients with endometriosis and controls. While Sharma et al found this similarity only in younger patients with endometriosis under 35 years, in the present study pregnancy rate in older endometriosis patients also was comparable to in vitro fertilization controls [17].
Similar to Lin et al [18], whose study showed an increased risk of placenta praevia in pregnant women with endometriosis, the group of women with endometriosis in this study suffered from placenta praevia noticeably more often than in the control group (0.8% vs 3%, p = 0.042). While placental abruption was not proven to be associated with endometriosis in the Chinese study, in this survey 2 women with endometriosis stated to have suffered from this condition, while none of the control group did. However, the numbers are too small for statistical analysis.
While, statistically, women with endometriosis were more likely to suffer from minor complications like Clavien-Dindo I (43.3% vs 32.5%, p = 0.005) and Clavien-Dindo II (29.7% vs 21%, p = 0.01), more severe complications which needed surgical, endoscopic or radiological intervention (Clavien-Dindo III) tended to be more likely to occur in the control group (14.2% vs 19.5%, p = 0.055). This may be because complications like early uterine contractions or cervical insufficiency, which proved to be more frequent in women with endometriosis, are treated conservatively. However, an episiotomy, which was needed more often in the control group (0.4% vs 7%, p = 0.002), counts as a surgical intervention and may therefore distort the picture.
Miscarriage rate is noticeably lower for women with endometriosis compared to the reference group (27.6% vs 34.9%, p = 0.038) [table 2]. However, comparing these results to the equivalent age group of pregnant women in Denmark between 1978-1992 (30-35 years vs. 34.4 years) the risk of miscarriage is noticeably higher for women suffering from endometriosis (12.4% vs 27.6%, p < 0.001) [19]. Relative risk for miscarriage in women with endometriosis compared to the average population is 2.23 (1.84-2.70). A Japanese cohort study suggests a much lower relative risk of 1.24 (1.20-1.29, 95% CI) [16]. However usually only women with severe cases of endometriosis and known history of pregnancy complications are referred to a specialized endometriosis centre like the University of Muenster, which may explain higher numbers in miscarriage for the control group.
Surprisingly, miscarriage rate was highest in the group of women without endometriosis who did not undergo infertility treatment but were only seeking consultation at the Center of Reproductive Medicine because of infertility (42.7%). The rate is noticeably higher than in the group of women with endometriosis who did not undergo infertility treatment (42.7% vs. 28.8%, p = 0.011). This may be because some of these women did not have problems to conceive but actually suffered from habitual abortion, having undergone miscarriage 5 to 6 times and thus increasing the overall miscarriage rate.
The rate of secondary cesarean sections in the group of women without endometriosis who had undergone infertility treatment showed a trend towards being lower than in the endometriosis group overall (20.8% vs 29.7%, p = 0.057). This is probably not due to fewer complications, but rather the consequence of the trend towards a higher rate of primary cesarean sections (23.6% vs 16.8%, p = 0.11) due to increased expectancy of complications, as meta analyses show an increased risk for obstetric and perinatal complications in this group [20]. Generally speaking, the risk for a secondary cesarean section seems to be noticeably higher in patients with endometriosis than in the average population in Germany (29.7% vs 15.9% p < 0,001) [21], while there is no significant difference in the number of planned cesarean sections (16.8% vs 15.4%, p = 0.283). This contradicts a Swedish survey stating that the adjusted odds ratio (OR) of pre-labour cesarean sections is 1.64 (1.54-1.75, 95% CI), whereas the OR for emergency cesarean sections was only 1.18 (1.10-1.27, CI 95%) [22]. However, the rate of emergency cesarean sections in Sweden is only 8.6 % and therefore the lowest out of the 31 European countries analysed in the study by Macfarlane et al, while the rate is at 15.9% in Germany [21]. This suggests that a cesarean section is indicated much faster in Germany than in Sweden, the patient characteristics differ between the countries or guidelines lead to a different kind of management. The higher rate of emergency cesarean sections may indicate that there were more unforeseen complications in this group. This may support recent data according to which adverse pregnancy outcomes and obstetrical complications are more common in women suffering from endometriosis [23, 24]. However, one must take into account that endometriosis can occur in various locations and with different severity and may therefore have very different effects on pregnancy. Therefore, ENZIAN score was used to further break down the results.
First, the outcome for women with ENZIAN A, B and C endometriosis were compared to all other ENZIAN categories. Miscarriage rate was similar between the groups. Obstetrical complications occurred noticeably more often in patients without ENZIAN A, B and C. Also, there were noticeably more secondary cesarean sections in this group. This finding is inconsistent with the results of a study conducted by Allerstorfer et al., which shows a higher rate of cesarean sections for women with A or C endometriosis [25]. However, Allerstorfer et al. compared these two groups mainly to patients with ENZIAN B endometriosis, which in contrast are included in our study group. To be able to compare the findings, the patients with ENZIAN-B, but without ENZIAN A/C were selected. In this group a secondary cesarean section was needed in 20.6% of the cases. There is no noticeable difference to patients with ENZIAN A/C, but without ENZIAN B, which were only slightly more likely to need a secondary cesarean section (23.7%, p = 0.357). The lower rate of cesarean sections for patients with ENZIAN A, B or C may have many reasons. One of them might be that in 3.6 % of the pregnancies in women without A, B or C endometriosis breech presentation occurred, while this was not reported to be the case in the 213 pregnancies with endometriosis in ENZIAN A, B and C locations. For women without breech position the risk of needing a secondary cesarean section decreased from 36.9% to 35.4%. Also, obstructed labour made an unplanned cesarean section necessary in 4.7% of cases in this group, while again this was not reported for women with A, B or C endometriosis. Even though numbers for pregnancy duration and type of delivery may be accurate, information given by patients about complications are expected to be lower than in reality, as some participants answered the survey in much less detail than others, often stating that they were in need of a secondary cesarean section, however leaving out the reason why this was necessary. For example other studies suggest that the incidence of obstructed labour in the general population is even higher than stated by the women without ENZIAN A, B or C (8.9% vs 4.7%) [26]. However, this might mostly be due to the design of the study, being dependent on information given by the patients themselves.
Miscarriage rate for patients with adenomyosis was similar to that of patients with deep infiltrating endometriosis. Secondary cesarean section was necessary more frequently in patients with adenomyosis. Women with adenomyosis had a significantly decreased probability of vaginal spontaneous delivery as opposed to the average German population (35.2% vs 62.2%, p-value < 0.001). As Leyendecker et al [27] suggest that adenomyosis presents itself with a dysfunction of the endometrial-subendometrial unit. As this disease can affect all myometrial uterine muscle layers this may increase the risk for obstructed labour. While prolonged labour occurs in 4.4% (n=2) of the cases of adenomyosis and only 1.5% (n=3) of the cases with endometriosis in other locations the numbers are too small to draw definitive conclusions.
As endometriosis of the uterus seems to increase the risk of complications during labour it may seem obvious that endometriosis of the rectovaginal space / vagina and the rectum may increase the risk of perineal laceration and bowel complications. However, women with endometriosis in these locations were not reported to suffer from lacerations more often than other women with endometriosis, suggesting that endometriosis does not generally weaken the tissue in this cohort. One woman with C1 endometriosis of the rectum reported that she suffered an inflammation of the colon.
Patients with bladder involvement had the lowest rate of spontaneous delivery compared to other groups with deep infiltrating endometriosis. Reported reasons were mainly cardiotocography abnormalities and obstructed labour. Numbers for miscarriage were similar to the average woman with endometriosis. While bladder endometriosis did not seem to have a negative impact on early pregnancies, this changed as the uterus grew and came closer to the bladder – and therefore to the location of endometrial lesions - during the pregnancy. Other studies show that pregnancy outcome is favourable after removal of bladder-endometriosis [28].
Limitations of this study mainly are due to limited sample size, retrospective design of the study, response rate, the control group suffering from infertility and possibly differing surgical techniques between the surgeons involved.