The presence of ovarian endometrioma adversely affect ovarian reserve and response to stimulation but not oocyte quality or IVF/ICSI outcomes: a retrospective cohort study

A total of 2067 women were enrolled in this study. The endometriosis group consisted of 154 patients with visual OMAs at the time of OPU (the OMAs group). The control group included 1913 patients without visual endometriosis and no prior surgery for OMAs. After PSM, the 154 women with OMAs were matched by age, BMI and duration of infertility at a 1:2 ratio to the 305 control women. For the OMAs group, the specific endometriosis phenotype was as follows: 120 (77.92%) had unilateral OMAs, while 34 (22.08%) had bilateral OMAs. The mean size of the OMA lesions was 36.80 ± 24.39 mm. OMAs diameter < 40 mm was found in 107/154 (69.48%) of these women and OMAs diameter ≥ 60 mm was found in 20/154 (12.99%) of these women. Lastly, 50 (32.25%) of patients in the OMAs group had previously undergone surgery for OMAs.

Patients’ overall demographics and baseline IVF characteristics were presented in Table 1 (left panel). Significant differences were observed in terms of BMI, duration of infertility, AMH, AFC, basal FSH, ovarian stimulation protocol, total Gn administered and number of follicles ≥ 10 mm on day of hCG between the two groups (P < 0.05). Comparison after PSM was also listed in Table 1 (right panel). No significant differences were observed between the two groups in regard to age, BMI, and duration of infertility, showing a valid matching in the enrolled population (P > 0.05). Patients in the OMAs group had significantly lower ovarian reserve markers, with a significantly lower mean serum AMH level (2.47 ± 2.34 ng/mL vs. 3.32 ± 2.82 ng/mL, p = 0.001) and AFC (8.08 ± 5.22 ng/mL vs. 12.29 ± 7.66 ng/mL, p = 0.000). However, basal serum FSH, LH and E2 levels were comparable between the two groups after matching (P > 0.05).

Table 1 Baseline characteristics and ovarian stimulation parameters in the endometrioma and control groups

The agonist protocol was more often prescribed in the OMAs group than in the control group (41.56% vs. 34.08%, 41.56% vs. 29.51%, respectively) before and after matching (P = 0.030, P = 0.010, respectively). Women with OMAs required significantly greater doses of Gn administered (2958.93 ± 1141.20 vs. 2643.20 ± 1086.46, P = 0.004) but a lower number of follicles on day of hCG than in the control group (11.06 ± 7.92 vs. 13.64 ± 9.17, P = 0.002). Meanwhile, the number of oocytes retrieved (8.27 ± 6.18 vs. 10.25 ± 6.97, p = 0.005) and the OSI (3.23 ± 3.07 vs. 4.93 ± 4.82, P = 0.000) of women with OMAs were significantly lower than those in the control group (Table 2), indicating a decreased ovarian response to stimulation among women with OMAs.

Table 2 Embryological data and IVF/ICSI outcomes in the endometrioma and control groups

Overall, the embryological data and IVF/ICSI treatment outcomes were summarized in Table 2. After matching, the number of MII oocytes was significantly lower in women with OMAs than in the control group (6.99 ± 5.41 vs. 8.33 ± 5.97, p = 0.040), as were the number of fertilized oocytes (6.20 ± 5.04 vs. 7.45 ± 5.54, p = 0.032), total embryos (6.34 ± 5.10 vs. 7.47 ± 5.58, p = 0.038), transplantable embryos (5.69 ± 4.78 vs. 6.72 ± 5.02, p = 0.035) and top-quality embryos (2.32 ± 2.48 vs. 2.82 ± 3.01, p = 0.038). However, the fertilization rate and the blastocyst rate were not significantly different between the two groups. Embryo transfer was achieved for 83.12% (128/154) of the women in the OMAs group and for 96.07% (293/305) of the women in the control group (p = 0.000). Similar proportions of cleavage or blastocyst embryos were transferred in both groups (p = 0.088).

In fresh cycles, the CPRs did not differ between women with OMAs vs. Controls (55.10% vs. 46.37%, p = 0.294). The LBRs were also similar between the two groups (48.98% vs. 36.96%, p = 0.140). In FET cycles, LBRs were similar between the OMAs and the control group (48.10% vs. 59.35%, p = 0.101), but CPRs was lower in women with OMAs than in the control group (53.16% vs. 66.45%, p = 0.048). The primary outcome measures, the cumulative CPRs (59.40% vs. 59.62%, p = 0.966) and the CLBRs (55.64% vs. 54.34%, p = 0.806) showed no significant differences between the OMAs and the control group.

The results of the univariate and multivariate analysis of factors affecting the CLBRs in patients undergoing IVF/ICSI were presented in Table 3. As regards to comparison between endometriosis vs. other infertility diagnosis, the results of univariate analysis showed a significantly lower CLBRs in patients with diminished ovarian reserve (DOR) compared with endometriosis (OR = 0.159; 95% CI: 0.069–0.367; p = 0.000), but no differences between endometriosis vs. tubal factor infertility, male factor infertility, anovulation, and unspecified infertility cause. However, in multivariate analysis, CLBRs was similar and did not differ significantly between women with endometriosis vs. DOR (p = 0.087). Meanwhile, age (OR = 0.836), AMH (OR = 1.318), AFC (OR = 1.099), follicles on day of hCG (OR = 1.113), OSI (OR = 1.290) and top-quality embryos (OR = 2.135) were associated with a significantly difference in CLBRs in univariate analysis. After multivariate analysis, age (OR = 0.861) and top-quality embryos (OR = 1.829) remained independent factors associated with CLBRs. In addition, AMH, AFC, stimulation protocol, OSI, number of follicles were not significantly associated with an increased CLBRs.

Table 3 Logistic regression analysis of factors affecting the cumulative live-birth rates per cycle in IVF/ICS patients

Next, in order to assess the impact of prior OMA surgery on the ovarian reserve and response, as well as IVF/ICSI outcomes, patients were further divided into two subgroups according to their previous history of ovarian surgery (Table 4). Among them, 104 had OMAs without prior ovarian surgery and 50 had OMAs and a history of prior cyst surgery. When compared to the OMAs without surgery group, patients with a history of prior cyst surgery had significantly lower ovarian reserve parameters (AMH and AFC), poor ovarian response parameters (OSI and number of follicles), thus resulted in significantly lower numbers of matured and fertilized oocytes and embryos. However, the oocyte maturity rate, fertilization rate and implantation rate were comparable within the two groups. Meanwhile, we observed a slight trend towards a lower proportion of CLBRs (50.00% vs. 57.14%) in patients with previous history of ovarian surgery, but the difference did not reach clinical significance when compared with those who had OMAs without previous surgery.

Table 4 IVF cycle characteristics and outcomes in endometriosis patients with and without prior surgery

To examine whether the IVF cycle characteristics and outcomes correlate with the size of OMAs, we performed a subgroup analysis based on patients with confirmed OMAs but without previous ovarian surgery (n = 104, Table 5). These patients were divided into three group according to the size of OMAs (categorized as follows: (A) OMAs diameter < 40 mm; (B) OMAs diameter ≥ 40 mm and < 60 mm; (C) OMAs diameter ≥ 60 mm). The baseline characteristics, ovarian stimulation and IVF/ICSI outcomes in our study were not significantly different in women with an OMA diameter ≥ 40 mm and < 60 mm as compared to those with OMAs diameter < 40 mm. However, women with OMAs diameter ≥ 60 mm had a significant lower AFC (3.85 ± 3.31 vs. 9.56 ± 5.31, p = 0.000), fewer follicles on the day of HCG (6.92 ± 7.94 vs. 12.67 ± 9.01, p = 0.034), fewer oocytes retrieved (5.08 ± 5.14 vs. 10.17 ± 7.08, p = 0.012) than those in women with OMAs diameter < 40 mm, indicating a decreased ovarian reserve. Likewise, number of fertilized oocytes (p = 0.011), embryos (p = 0.017), transplantable embryos (p = 0.011) and top-quality embryos (p = 0.037) were also lower in women with OMAs diameter ≥ 60 mm when compared to the OMAs diameter < 40 mm group. As regard to IVF/ICSI outcomes, a trend towards a lower CLBRs was observed in the OMAs diameter ≥ 60 mm group compared with OMAs diameter < 40 mm group (41.67%, vs. 58.73%, p = 0.275), but no significant difference was achieved. The result of spearman’s correlation showed that there was a negative correlation between OMA size and AFC levels in patients with unoperated OMAs (r = -0.264, p = 0.007).

Table 5 IVF cycle characteristics and outcomes in patients with unoperated OMAs according to the cyst size Table 6 IVF characteristics in ovaries with and without endometrioma in patients with unoperated unilateral OMAs.

Furthermore, another subgroup analysis was performed according to the laterality of OMAs (bilateral or unilateral), and the results were showed in Table S1. AMH, AFC, number of follicles on day of hCG, oocytes retrieved, MII oocytes, fertilized oocyte and embryos were lower in patients with bilateral OMAs than those in patients with unilateral OMAs, but no significant difference was found. In consequence, the IVF/ICSI outcomes (i.e. CPRs, LBRs and CLBRs) were not significantly different in women with bilateral OMAs as compared to unilateral OMAs. Moreover, comparisons between ovaries with OMAs and the contralateral ovaries in women with unoperated unilateral OMAs are presented in Table 6. Ovaries with OMAs had a significantly lower AFC (3.80 ± 2.86 vs. 4.90 ± 3.15, P = 0.006) but a similar number of follicles on day of hCG (5.11 ± 4.32 vs. 5.47 ± 4.88, P = 0.544) and oocytes retrieved (3.97 ± 3.20 vs. 4.37 ± 3.53, P = 0.355) when compared with the contralateral ovaries.

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