In this study, 176 infertile women with both EM and AM had laparoscopic surgery and completed an outpatient follow up.
Few studies have concentrated on the pregnancy outcomes of women with both AM and EM; most research reported only EM or AM patients or grouped the two diseases together. Chloé Maignien et al.[12] studied 359 infertile EM patients and the pregnancy and live birth rates were 44% and 32%, respectively. Our results were a bit higher, perhaps because of the longevity of our follow up. Some patients were able to have a natural live birth even after repeated IVF-ET failure.
EM phenotypes seemed to impact pregnancy outcomes, as there were significant differences between the live-birth group and stillbirth group. Our previous results verified the presence of follicles in the cyst walls of the endometrioma in paraffin sections[13] and that FSH levels were significantly decreased after laparoscopic bilateral ovary endometrioma resection[14]. Vercellini et al. retrospectively analyzed 419 patients who achieved natural conception and divided them into four groups according to the type of EM. The total pregnancy loss rate was 20.8%, which was close to ours (20.03%). They also observed a higher miscarriage rate in women with ovarian endometriomas (26%) than in those with the peritoneal type (12%)[15]. However, these findings were contrary to the report done by Chloé Maignien et al.[12]. In his study, the live birth rates per cycle were 13.7%, 16.5,% and 16% in peritoneal, ovarian, and deep infiltrating EM subgroups (p = 0.82), respectively.
In addition to the reduced oocyte yield, reduced fertilization rate (FR), and increased miscarriage rate, AM and EM were also reported to be related to several obstetrical and fetal complications. However, the evidence is still scanty and conflicting. A meta-analysis in 2019[16] including 104 papers demonstrated that EM could be associated with preterm delivery (OR 1.38, CI 1.01–1.89), caesarean section delivery (OR 1.98 CI 1.64–2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07–1.55). It is noteworthy that no OR exceeded three. Two other systematic reviews failed to draw conclusions on obstetrical complications related to EM except for preterm delivery[17] and placenta previa[18]. The results of this study showed a preterm birth rate of 16.84% and placenta previa rate of 7.36%, which are findings slightly higher than in Benaglia L’s report. In his retrospective, matched, case-control study[19], the rate of preterm birth was similar between the EM and non-EM groups (14% and 14%, respectively, p = 0.89), while placenta previa was more common in women with EM than in the control group (6% versus 1%, respectively; p = 0.006, OR 4.8, 95% CI: 1.4–17.2). A possible explanation for this might be that our cases had patients with both EM and AM. In a multicenter, retrospective, questionnaire survey[20] including 272 pregnant women with AM from 65 facilities, the preterm delivery rate was reported to be as high as 24.4%. Several studies further analyzed the clinical factors that affect pregnancy outcomes. In a retrospective study of 631 women with EM who became pregnant by ART [21], the reported incidence of preterm delivery or abnormal placental positioning didn’t increase in stages I–III, but increased significantly in stage IV. Dr. Kim and colleagues[22] reported a preterm labor rate of 24.56% in a retrospective study and found that uterine wall thickness in the second trimester was related to subsequent preterm delivery. In our study, the size of uterus was also found to be significantly different between the two groups.
The etiology of infertility might include disordered inflammatory factors like prostaglandin (PG) production (PGE2 and PGF2a), cyclooxygenase 2 (COX-2)[23], abnormal ER- and PR-mediated signaling pathways associated with progesterone resistance[24], impaired trophoblast invasiveness, and uterine contractility[25]. These can also be related to failure of the physiologic transformation of spiral arteries in the inner myometrial segment, or junctional zone (JZ). Alterations of the JZ in women with EM and AM can influence vascular resistance of JZ spiral arteries at the onset of decidualization[25] and lead to incomplete spiral artery remodeling and the reduction of placental blood flow[26]. The mechanism is complex, and the existing results are debatable. The influence of co-existing EM and AM on pregnancy is not simply superimposed, but rather the two diseases interact with each other.
The strength of this study is its diagnosis. The golden standard of AM diagnosis is based on histological specimens, which is an invasive technique and has a potential of uterine rupture during pregnancy and delivery. Therefore, non-invasive technics like ultrasound and MRI are preferred. MRI, with a sensitivity from 78–88% and specificity from 67–93% [27], was traditionally considered to be more accurate than ultrasound. However, with the development of high-quality transvaginal ultrasound (TVUS), a systematic review including 10 studies (1168 records) proved that the two techniques are comparable[28]. The accuracy of the ultrasound in AM diagnoses is high with a mean sensitivity of 0.72 (95% CI: 0.65–0.79), specificity of 0.81 (95% CI: 0.77–0.85), and area under the curve (AUC) of 0.85[29, 30]. Additionally, ultrasounds are much cheaper and more convenient. The diagnoses of EM and its subtypes are based on laparoscopic surgery, which is the gold standard and quite reliable. However, women referred to our hospital may have had particularly severe forms of AM, EM, or repeated IVF failure, which introduces potential selection and comparison bias. Second, the follow up didn’t include an analysis of IVF details. Most patients went to their local ART center for controlled ovarian stimulation and IVF-ET and could hardly recall the details, remembering only the final results. There are several other limitations to these results. First, our study is retrospective. Second, the number of cases was limited and we could not perform subtype analyses according to the obstetric complications. Third, other disputed factors were not included, such as the excision of DIE[31], use of GnRHa[32], and complete removal of endometrial lesions [33]. Fourth, this study only includes patients that needed laparoscopic surgery. Although dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia, and infertility often occur, a third of the women were asymptomatic[27] and we are worried about the extent to which this will affect our fertility and sterility rates.