Endometriosis (EMS) is a common disorder in women of reproductive age and one of the leading causes of female infertility. The concept of infertility associated with EMS was first proposed by Buyalos and Agarwal in 2000, which clarified the reciprocal relationship between infertility and EMS. Although several guidelines and consensus statements on the diagnosis and management of EMS have been published both domestically and internationally, standardized protocols specifically for infertility associated with EMS remain insufficient. In addition, patients with EMS-related infertility present high clinical heterogeneity, and clinical concepts are continuously updated. How to achieve standardized and individualized treatment has become a major challenge in obstetrics and gynecology and reproductive medicine.
To further standardize the clinical diagnosis and treatment of infertility associated with EMS, the Professional Committee on Fertility Preservation of the Chinese Maternal and Child Health Association, together with the Reproductive Medicine Branch of the China International Exchange and Promotion Association for Medical and Healthcare, organized multidisciplinary experts to develop this consensus through multiple rounds of discussion and formulate recommendations, aiming to provide reference and guidance for clinical practice in China.
Consensus Development Methodology
This consensus adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Evidence was classified into four quality levels: high (A), moderate (B), low (C), and very low (D). The strength of recommendations was defined as strong (Grade 1) or weak (Grade 2). For clinical questions lacking direct evidence, good practice points (GPPs) were formulated based on experts’ clinical experience. The detailed grading criteria are shown in Table 1.
Recommendations and Evidence Base
This consensus covers 9 clinical questions and 15 recommendations, summarized in Table 2.
1. Impact of EMS on Female Fertility
EMS affects 5%–10% of reproductive-age women worldwide. The incidence of infertility in EMS patients is significantly higher than in the general population, reaching 40%–50%, while EMS is present in 20%–50% of infertile women. EMS causes infertility by impairing multiple key reproductive processes, including pelvic anatomy, ovulatory function, and endometrial receptivity.
A large prospective study showed that the risk of infertility in EMS patients under 35 years old was 1.77 times that of women without EMS. Without intervention, the spontaneous pregnancy rate was approximately 52.9% in mild EMS, 25% in moderate EMS, and no spontaneous conception was observed in severe EMS during follow-up.
Two systematic reviews and meta-analyses confirmed an increased miscarriage risk in EMS patients: one reported an OR of 1.30 (95% CI: 1.25–1.35), and the other an OR of 1.81 (95% CI: 1.44–2.28). Furthermore, EMS is associated with lower oocyte yield and fertilization rates in assisted reproductive technology (ART). Ovarian EMS negatively affects the number of retrieved oocytes (MD = -1.22, 95% CI: -1.96 to -0.49) and mature oocytes (MD = -2.24, 95% CI: -3.4 to -1.09). A 2022 systematic review and meta-analysis also confirmed fewer oocytes retrieved in EMS patients (MD = -1.51, 95% CI: -2.06 to -0.95).
Expert recommendation:EMS reduces the spontaneous pregnancy rate (1A), may increase the risk of miscarriage (2B), and negatively affects oocyte retrieval in ART (2B). Detailed reproductive history should be obtained to identify coexisting EMS-related infertility. Treatment goals should not be limited to cyst resection, pain relief, and recurrence prevention; fertility needs and the impact of interventions on reproductive function must be fully considered. Joint evaluation by reproductive and gynecologic specialists is recommended for individualized planning when necessary.
2. Fertility Assessment in EMS-Related Infertility
The Endometriosis Fertility Index (EFI), developed by Adamson and Pasta in 2010, is a simple, validated postoperative scoring system that predicts non-ART spontaneous pregnancy rates in patients with different surgical stages of EMS. It includes historical factors (age, duration of infertility, prior pregnancy) and surgical factors (least function score of ovaries and fallopian tubes, endometriotic lesion score, ASRM score, and total ASRM score), ranging from 0 to 10. Higher scores predict higher spontaneous pregnancy rates.
A systematic review and meta-analysis of 4,598 patients from 17 studies across 8 countries showed that at 36 months postoperatively, the cumulative live birth rates (CLBR) for EFI 0–2, 3–4, 5–6, and 7–8 were 10%, 18%, 44%, and 55%, respectively, and 69% for EFI 9–10, with an AUC of 72% (95% CI: 65%–80%).
A prospective study using EFI to guide postoperative management showed that patients with EFI ≤4 proceeded directly to ART; EFI 5–6 attempted natural conception for 6 months before ART; EFI ≥7 attempted for 9 months. The overall pregnancy rates were 42.3%, 67.9%, and 87.7%, respectively.
Expert recommendation:The EFI scoring system is an effective tool for predicting postoperative spontaneous pregnancy in EMS-related infertility. Fertility guidance should be based on EFI, and patients with low scores should be advised to undergo ART promptly (1A).
3. Treatment of EMS-Related Infertility
3.1 Medical Therapy
Most medications used for EMS-related pain and recurrence prevention are ovarian function-suppressing hormones, such as progestins, GnRH agonists (GnRH-a), and combined oral contraceptives. However, their efficacy for improving fertility in EMS-related infertility remains unproven.
A Cochrane review showed that ovarian suppression therapy did not improve fertility compared with placebo or no treatment (OR = 0.97, 95% CI: 0.68–1.34).
Although hormones are often used as adjuvants to surgery, consistent evidence is lacking. A 2020 Cochrane review including 262 patients found no clear benefit of preoperative hormonal therapy on pregnancy rate (RR = 1.16, 95% CI: 0.99–1.36). Eleven RCTs (n = 932) suggested that postoperative medical therapy might improve pregnancy rates (RR = 1.22, 95% CI: 1.06–1.39), but this included both spontaneous and ART pregnancies without separate analysis. The ESHRE guideline recommends against postoperative ovarian suppression solely to improve pregnancy rates in women seeking conception.
Expert recommendation:Ovarian function-suppressing hormonal therapy alone does not improve pregnancy rates in EMS-related infertility (1A). Preoperative adjuvant medical therapy has uncertain benefit (2B). Although such therapy does not improve postoperative pregnancy rates, it may be used postoperatively to relieve pain and reduce recurrence if conception is not attempted immediately (2C).
3.2 Surgical Therapy
The ASRM staging is widely used for EMS. A 2020 Cochrane review of 528 patients with ASRM stage I–II EMS showed that laparoscopic surgery improved clinical pregnancy rate compared with diagnostic laparoscopy alone (OR = 1.89, 95% CI: 1.25–2.86). Another meta-analysis (n = 933) confirmed higher pregnancy and live birth rates after laparoscopy.
For ASRM III–IV and deep infiltrating endometriosis (DIE), surgery can resect lesions and relieve pain, but high-quality evidence for improved pregnancy rates is lacking. Laparoscopic benefits appear less pronounced in moderate–severe disease.
Surgery may impair ovarian reserve, especially in bilateral endometriomas. A 2024 systematic review showed that ovarian reserve decreased after cystectomy, with a greater reduction in bilateral cases (AMH to 39.5% of baseline) than unilateral (57.0%).
Expert recommendation:Surgical decision-making must be individualized, considering age, ovarian reserve, infertility duration, unilateral/bilateral cysts, other infertility factors, and ASRM stage (1A). Laparoscopy is recommended for ASRM I–II EMS-related infertility (1A). For ASRM III–IV and DIE, balanced decisions between reproductive surgery and ART are needed. ART should be prioritized in patients with diminished ovarian reserve, impaired tubal function, low EFI, male factor, or recurrent EMS (2C).
3.3 Assisted Reproductive Technology (ART)
(1) Management of ovarian endometriomas before ART
Surgery for ovarian endometriomas ≥4 cm before ART is controversial. Multiple studies and systematic reviews show no improvement in clinical pregnancy or live birth rates after cystectomy or aspiration before ART.
However, transvaginal aspiration may improve ovarian response. Several studies reported higher oocyte yield after aspiration compared with cystectomy.
Surgery may be considered for rapidly growing cysts, suspected malignancy, risk of rupture or abscess, or interference with oocyte retrieval. Malignancy must be excluded before aspiration.
For patients with cryopreserved embryos and cysts >4 cm, laparoscopic cystectomy for primary cysts or aspiration for recurrent cysts may be performed according to Chinese guidelines.
Expert recommendation:Surgery for ovarian endometriomas before ART is not recommended to improve pregnancy or live birth rates (2B). Cyst aspiration may be performed to facilitate oocyte retrieval, but malignant risk must be evaluated (GPP, C).
(2) Ovarian stimulation protocols for ART
Numerous studies show similar clinical pregnancy and live birth rates between GnRH-a and GnRH antagonist protocols. The GnRH-a protocol may yield more oocytes, while the antagonist protocol is shorter and requires less gonadotropin.
Extended GnRH-a long protocols (3–6 months) have shown inconsistent benefits and are not superior. A 2022 RCT showed that PPOS (MPA + hMG) had similar outcomes to the extended GnRH-a protocol with lower gonadotropin consumption.
Evidence for pre-treatment with dienogest or oral contraceptives before ART remains inconclusive.
Expert recommendation:Both GnRH-a and GnRH antagonist protocols are first-line options for COS in EMS patients (1A). The extended GnRH-a long protocol is not preferred due to unclear benefit (2B). Insufficient evidence supports routine pre-treatment before ART to improve pregnancy rates (2C).
(3) Embryo transfer strategies
A 2022 systematic review (n = 3010) showed that frozen-thawed embryo transfer (FET) was associated with higher live birth rates and lower miscarriage rates compared with fresh embryo transfer, although evidence was moderate.
Common endometrial preparation regimens for FET include natural cycle, HRT, and GnRH-a + HRT. Recent studies show no significant differences in pregnancy or live birth rates among these regimens, regardless of GnRH-a injection times.
Expert recommendation:FET may be associated with higher live birth and lower miscarriage rates than fresh transfer in EMS-related infertility, but further validation is required before routine use (2B). GnRH-a + HRT is commonly used but has no proven superiority over other regimens (GPP, C).
4. Fertility Protection and Preservation in EMS Patients
Severe EMS (especially bilateral endometriomas) and surgery may reduce ovarian reserve. Major fertility preservation guidelines list severe and recurrent ovarian endometriomas as indications.
Embryo cryopreservation is the most established method and first choice for married women.
Oocyte cryopreservation is effective, especially for young women without a partner.
Ovarian tissue cryopreservation is limited in EMS and requires caution.
Surgical hemostasis techniques affect ovarian reserve: suture hemostasis is associated with better ovarian function preservation than bipolar coagulation or ultrasonically activated devices.
Expert recommendation:The main fertility preservation methods for EMS are embryo and oocyte cryopreservation, with embryo cryopreservation being the most established. Ovarian function should be protected during surgery; suture hemostasis may help preserve ovarian reserve (2B).
Conclusion
EMS is closely associated with infertility. Early fertility assessment using EFI and individualized, evidence-based interventions are essential. Long-term, systematic management is important given the chronic and recurrent nature of EMS.
Source:中国妇幼保健协会生育力保存专业委员会,中国医疗保健国际交流促进会生殖医学分会. 子宫内膜异位症相关不孕诊治专家共识（2025年）[J]. 中华生殖与避孕杂志,2025,45(12)：1221-1231.DOI:10.3760/cma.j.cn101441-20250729-00320
Edited by: Lily