Reproductive and postsurgical outcomes of infertile women with deep infiltrating endometriosis | BMC Women’s Health

The situation is complicated and changeable for DIE patients with infertility. Additional factors, such as the patient’s age, ovarian function, and surgical history, need to be considered. DIE surgery can significantly reduce pain and improve quality of life [9, 10]. However, there is still controversy regarding whether surgery improves fertility. Our study evaluated the effect of DIE surgery on reproductive outcomes.

Most studies have reported that the overall pregnancy rate after DIE is 34–84.5% (CI 95 = 65.1–71.9%) [11,12,13]. In our study, the postoperative pregnancy rate among women with DIE was 61.82%, which is similar to most research results. A systematic review [14] showed that surgery for bowel DIE may improve the spontaneous pregnancy rate and have positive effects on IVF outcomes. However, surgical complications will extend the interval between surgery and pregnancy. Roman et al. [15] showed that the probabilities of achieving pregnancy after colorectal DIE surgery at 12, 24, 36 and 48 months postoperatively were 33.4% (95% CI: 20.6–51.3%), 60.6% (44.8–76.8%), 77% (61.5–89.6%) and 86.8% (72.8–95.8%), respectively. Surgery can also result in a high pregnancy rate for women with ureteral DIE [16, 17].

There are also several reports suggesting that DIE surgery can improve the pregnancy outcomes of ART. A retrospective cohort study showed that cumulative live birth rates were significantly higher for women who underwent first-line surgery followed by ART than for those who underwent first-line ART [18]. Soriano et al. [19] suggested that extensive laparoscopic surgery could improve IVF outcomes for patients with severe endometriosis and repeated in vitro fertilization failures. Similarly, Breteau et al. [20] discovered that infertile women with ≥ 2 IVF–ICSI failures should be referred for surgery and that the mean time from surgery to pregnancy is 11.1 months, which is similar to the median time to pregnancy of 12 months following attempts to conceive for all pregnancies. Therefore, surgery for DIE does not routinely delay conception.

DIE surgery is complicated, involves multiple organs and has a high risk of complications. Will the complications affect pregnancy outcomes? The answer to this question may influence the decision to perform DIE surgery for both doctors and patients. Ferrier et al. [21] analyzed the fertility outcomes of women who wished to conceive after a severe complication of surgery for colorectal endometriosis. The overall pregnancy rate was 41.2%, and 80% of women conceived spontaneously, which appeared satisfactory. The occurrence of a rectovaginal fistula, anastomotic leakage or deep pelvic abscess negatively impacts fertility outcomes. Therefore, patients with septic complications may benefit from rapid ART procedures. In our study, there were no serious complications. This may be because we have an experienced surgical team.

Considering the high risk of complications of DIE surgery, some researchers suggest first-line ART rather than surgery for DIE patients with infertility, especially those with tubal or male infertility factors [22]. However, the impact of DIE lesions on ART and obstetric complications is worth considering. A notable finding was that the number of DIE lesions was negatively correlated with ART outcomes [23]. Several studies have shown that DIE lesions can increase the risk of premature delivery, placenta previa, placental abruption and gestational hypertension. The cesarean section rate and the incidence of surgical complications (such as hysterectomy, peritoneal hemorrhage and bladder injury) in DIE patients were significantly higher than those in the normal group [24, 25].

There was no difference in rAFS scores between the pregnancy and nonpregnancy groups. The reason may be that the rAFS stages poorly reflect the severity of endometriosis-associated pain and infertility. Furthermore, the classification system has limited value in scoring DIE [26]. The ENZIAN classification has been recommended to classify DIE by the European Society of Gynecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society [27, 28]. Additionally, the new #ENZIAN classification has been proposed and includes endometriosis of the peritoneum, endometriosis of the ovaries and the extent of adnexal adhesions, which makes up for the insufficiency of the ENZIAN classification [29]. However, the greatest challenge of the current classification systems seems to be their poor correlation with symptoms and infertility. Currently, we are completing the ENZIAN classification and analyzing its correlation with infertility, and the results will be presented in future articles.

The EFI has been proven to be a useful model for predicting pregnancy outcomes. Tomassetti et al. [30] discovered that the EFI is reliably reproducible and should be used for postoperative management and counseling of patients about their reproductive options. A systematic review and meta-analysis demonstrated that natural conception is the first choice for women with an EFI score of 6–10 [31]. In our study, we found that a lower EFI score (EFI < 8) was a risk factor for infertility. We suggest that patients with lower EFI scores (EFI < 8) should not be advised to undergo long-term expectant treatment and that postoperative IVF–ET may be a good choice. To explore this further, we performed a hierarchical analysis of EFI scores. We found that the least function (LH) scores of most patients (90.9%) were above four. Only 60% of DIE patients had ovarian endometriosis, and the anatomy and function of the fallopian tubes and ovaries were not seriously damaged. This may explain why the EFI scores were high for DIE patients with infertility. From another perspective, the mechanism by which DIE causes infertility is different from that of other endometriosis types.

AMH levels and antral follicular count (AFC) are considered valuable indicators of ovarian reserve. However, AFC has limitations in estimating the ovarian reserve of the ovary with the endometrioma [32]. The presence of a large endometrioma may impair the sonographic identification of small follicles adjacent to the cyst, and consequently, the ovarian reserve could be underestimated. Additionally, reports on the relationship between AMH and pregnancy in postoperative DIE are variable. Stochino-Loi et al. [33] found that preoperative AMH level did not significantly impact the probability of postoperative pregnancy when spontaneous conception and conception after ART were considered together. Reports of the relation between AMH or AFC and reproductive outcomes in postoperative DIE remain unconfirmed and is worth exploring in the future to help physicians and patients make clinical decisions.

In our study, there was no difference in residual lesions between the pregnancy and nonpregnancy groups. Qi Cao et al. [34] reported similar results. However, we discovered that there were more patients who underwent cautery surgery in the nonpregnancy group, which suggested that complete surgical excision of DIE is the first choice of surgical treatment. GnRH agonists are widely used in the treatment of endometriosis symptoms. However, it is controversial whether postoperative GnRHa improves DIE pregnancy outcomes. Although 79.41% of pregnant patients used postoperative GnRHa in our study, we discovered that the administration of postoperative GnRHa could improve the pregnancy rate only of patients with incomplete excision and not that of patients with complete excision. Bergenheim et al. [35] also found that infertile women with endometrioma(s) treated with radical surgery and long-term GnRHa downregulation immediately prior to IVF had a modest LBR after the first cycle, possibly due to immoderate suppression of ovarian function. Considering that the long-term use of GnRH agonists is associated with hypoestrogenic side effects and a substantial reduction in bone mineral density [36], our results suggest that postoperative GnRHa should be administered for patients with incomplete excision but that it is not necessary to routinely use postoperative medical treatment for patients with a reproductive desire who undergo complete surgical excision of DIE lesions.

Most patients in our study had significant improvements in gastrointestinal symptoms, dysmenorrhea and quality of life after DIE surgery. Although there was no obvious difference in FSFI scores, significant improvement in dyspareunia was observed. All these results indicated that DIE surgery could effectively improve pain symptoms. D’Alterio et al. [37] demonstrated that many medical and surgical treatments could demonstrate benefits in pain control and quality-of-life improvement. Overall, the surgical approach for severe DIE may be more effective and decisive. Therefore, surgery is required for DIE patients with obvious pain symptoms or clinically relevant intestinal or ureteral stenosis. Surgery might also be considered in young women who have repeated IVF failures [20]. Recent studies have also considered whether new technologies could improve surgical treatments for endometriosis; several have already found that the use of diode laser, plasma or CO2 lasers could improve pain symptoms and quality of life in selected cases [38, 39]. For DIE patients in our hospital, we used ultrasonic and plasma energy or cold scissors in nodule excision procedures, which also had feasible and effective results. More new energy instruments are worth exploring. However, some researchers suggest that surgery cannot be recommended for asymptomatic infertile women whose main goal is to treat infertility, as evidence to support such an approach is still scant. The use of an MDT comprising a gynecologist, reproductive specialist, urologist, colorectal surgeon, radiologist and counselor/psychologist is considered good practice in the management of endometriosis. Decisions should be tailored according to individual needs after the patient is provided with information on the potential benefits, harm, and costs of each treatment alternative [40, 41].

The major limitation of our study is related to its retrospective and nonrandomized design. In the context of infertility, only a randomized trial comparing first surgery to first ART could resolve this challenging issue. The sample size was not large enough to draw conclusions on some subgroups, such as patients who underwent incomplete surgery and lesion segments with anastomosis surgery. The strength of our study was that the baseline data of our patients were strictly matched. Rigorous prospective data were recorded by a dedicated clinical researcher who managed the follow-up of patients, with a very low dropout rate.