MULTIMODAL TREATMENT STRATEGIES IN ENDOMETRIOSIS: A CONTEMPORARY SYSTEMATIC REVIEW OF MEDICAL AND SURGICAL MANAGEMENT
Abstract
Introduction: Endometriosis is a chronic, estrogen-dependent disorder characterized by ectopic endometrial-like tissue, chronic pelvic pain and impaired fertility. Optimal management requires balancing symptom control, recurrence prevention and preservation of reproductive potential. This review synthesizes evidence on contemporary pharmacological, postoperative and non-pharmacological strategies to inform multidisciplinary care.
Methodology: A literature review of PubMed, Scopus, and Google Scholar was performed, focusing on recent systematic reviews and meta-analyses evaluating surgical, pharmacological, non-pharmacological, and assisted reproductive strategies for endometriosis.
Results: Progestogens (notably dienogest) and continuous/extended COCs reduce dysmenorrhea and chronic pelvic pain and serve as viable long-term maintenance. Oral GnRH antagonists provide rapid, dose-dependent analgesia with add-back strategies mitigating hypoestrogenic harms. Surgical excision may yield superior symptom relief and lower recurrence in selected phenotypes but risks ovarian reserve loss, tissue-paring techniques can attenuate this effect. Postoperative hormonal suppression (≥6–12 months) reduces recurrence. Integrated non-pharmacological modalities improve pain coping, adherence and HRQoL. Endometriomas and deep disease negatively affect ovarian response and implantation, supporting individualized pre-ART planning
Conclusion: Effective endometriosis management requires an individualized, multimodal approach integrating surgery, medical therapy, supportive care, and fertility planning. Holistic strategies enhance quality of life, reduce pain, and optimize reproductive outcomes. Interdisciplinary coordination is key to tailoring therapy according to patient phenotype, reproductive goals, and disease severity.
References
Zakhari, A., Delpero, E., McKeown, S., Tomlinson, G., Bougie, O., & Murji, A. (2021). Endometriosis recurrence following post-operative hormonal suppression: a systematic review and meta-analysis. Human reproduction update, 27(1), 96–107. https://doi.org/10.1093/humupd/dmaa033
Liu, Y., Gong, H., Gou, J., Liu, X., & Li, Z. (2021). Dienogest as a Maintenance Treatment for Endometriosis Following Surgery: A Systematic Review and Meta-Analysis. Frontiers in medicine, 8, 652505. https://doi.org/10.3389/fmed.2021.652505
Wu, H., Liu, J. J., Ye, S. T., Liu, J., & Li, N. (2024). Efficacy and safety of dienogest in the treatment of deep infiltrating endometriosis: A meta-analysis. European journal of obstetrics, gynecology, and reproductive biology, 297, 40–49. https://doi.org/10.1016/j.ejogrb.2024.03.032
Xin, L., Ma, Y., Ye, M., Chen, L., Liu, F., & Hou, Q. (2023). Efficacy and safety of oral gonadotropin-releasing hormone antagonists in moderate-to-severe endometriosis-associated pain: a systematic review and network meta-analysis. Archives of gynecology and obstetrics, 308(4), 1047–1056. https://doi.org/10.1007/s00404-022-06862-0
Delanerolle, G., Ramakrishnan, R., Hapangama, D., Zeng, Y., Shetty, A., Elneil, S., Chong, S., Hirsch, M., Oyewole, M., Phiri, P., Elliot, K., Kothari, T., Rogers, B., Sandle, N., Haque, N., Pluchino, N., Silem, M., O'Hara, R., Hull, M. L., Majumder, K., … Raymont, V. (2021). A systematic review and meta-analysis of the Endometriosis and Mental-Health Sequelae; The ELEMI Project. Women's health (London, England), 17, 17455065211019717. https://doi.org/10.1177/17455065211019717
Del Pino-Sedeño, T., Cabrera-Maroto, M., Abrante-Luis, A., González-Hernández, Y., & Ortíz Herrera, M. C. (2024). Effectiveness of psychological interventions in endometriosis: a systematic review with meta-analysis. Frontiers in psychology, 15, 1457842. https://doi.org/10.3389/fpsyg.2024.1457842
Wang, J. Y., Zhang, Y., & Ding, J. (2025). Oral Gonadotropin-Releasing Hormone Antagonists in the Treatment of Endometriosis: Advances in Research. Journal of clinical medicine research, 17(6), 299–308. https://doi.org/10.14740/jocmr6236
Somigliana, E., Li Piani, L., Paffoni, A., Salmeri, N., Orsi, M., Benaglia, L., Vercellini, P., & Vigano', P. (2023). Endometriosis and IVF treatment outcomes: unpacking the process. Reproductive biology and endocrinology : RB&E, 21(1), 107. https://doi.org/10.1186/s12958-023-01157-8
Mappa, I., Page, Z. P., Di Mascio, D., Patelli, C., D'Antonio, F., Giancotti, A., Gebbia, F., Mariani, G., Cozzolino, M., Muzii, L., & Rizzo, G. (2024). The Effect of Endometriosis on In Vitro Fertilization Outcomes: A Systematic Review and Meta-Analysis. Healthcare (Basel, Switzerland), 12(23), 2435. https://doi.org/10.3390/healthcare12232435
Qing, X., He, L., Ma, Y., Zhang, Y., & Zheng, W. (2024). Systematic review and meta-analysis on the effect of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) on pregnancy outcomes in women with endometriosis following conservative surgery. BMC pregnancy and childbirth, 24(1), 237. https://doi.org/10.1186/s12884-024-06430-1
Mitchell, J. B., Chetty, S., & Kathrada, F. (2022). Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety. BMC women's health, 22(1), 526. https://doi.org/10.1186/s12905-022-02122-0
Muzii, L., Di Tucci, C., Galati, G., Carbone, F., Palaia, I., Bogani, G., Perniola, G., Tomao, F., Kontopantelis, E., & Di Donato, V. (2023). The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis. Reproductive sciences (Thousand Oaks, Calif.), 30(11), 3135–3143. https://doi.org/10.1007/s43032-023-01266-0
Piacenti, I., Tius, V., Viscardi, M. F., Biasioli, A., Arcieri, M., Restaino, S., Muzii, L., Vizzielli, G., & Porpora, M. G. (2025). Dienogest vs. combined oral contraceptive: A systematic review and meta-analysis of efficacy and side effects to inform evidence-based guidelines. Acta obstetricia et gynecologica Scandinavica, 104(8), 1424–1432. https://doi.org/10.1111/aogs.15145
Brown, J., Crawford, T. J., Datta, S., & Prentice, A. (2018). Oral contraceptives for pain associated with endometriosis. The Cochrane database of systematic reviews, 5(5), CD001019. https://doi.org/10.1002/14651858.CD001019.pub3
Cooper, K. G., Bhattacharya, S., Daniels, J. P., Horne, A. W., Clark, T. J., Saridogan, E., Cheed, V., Pirie, D., Melyda, M., Monahan, M., Roberts, T. E., Cox, E., Stubbs, C., Middleton, L. J., & PRE-EMPT Collaborative Group (2024). Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial. BMJ (Clinical research ed.), 385, e079006. https://doi.org/10.1136/bmj-2023-079006
Csirzó, Á., Kovács, D. P., Szabó, A., Szabó, B., Jankó, Á., Hegyi, P., Nyirády, P., Ács, N., & Valent, S. (2024). Comparative Analysis of Medical Interventions to Alleviate Endometriosis-Related Pain: A Systematic Review and Network Meta-Analysis. Journal of clinical medicine, 13(22), 6932. https://doi.org/10.3390/jcm13226932
Donnez, J., Becker, C., Taylor, H., Carmona Herrera, F., Donnez, O., Horne, A., Paszkowski, M., Petraglia, F., Renner, S. P., Patel, A., Boolell, M., Bestel, E., & Dolmans, M. M. (2024). Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3). Human reproduction (Oxford, England), 39(6), 1208–1221. https://doi.org/10.1093/humrep/deae076
Giudice, L. C., As-Sanie, S., Arjona Ferreira, J. C., Becker, C. M., Abrao, M. S., Lessey, B. A., Brown, E., Dynowski, K., Wilk, K., Li, Y., Mathur, V., Warsi, Q. A., Wagman, R. B., & Johnson, N. P. (2022). Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet (London, England), 399(10343), 2267–2279. https://doi.org/10.1016/S0140-6736(22)00622-5
Miller, C. E., Kim, J. H., Kroll, R., Simon, J. A., Soliman, A. M., Thomas, J. W., Xu, Y., Ng, J., & Snabes, M. C. (2024). Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: twelve months of an ongoing randomized phase 3 trial. American journal of obstetrics and gynecology, 231(6), 630.e1–630.e13. https://doi.org/10.1016/j.ajog.2024.06.040
Donnez, J., Petraglia, F., Taylor, H., Becker, C., Becker, S., Carmona Herrera, F., Paszkowski, M., Bestel, E., Hori, S., & Dolmans, M. M. (2025). Two-year follow-up study (PRIMROSE 3) to assess bone mineral density in subjects with uterine fibroids completing the PRIMROSE 1 and PRIMROSE 2 linzagolix trials. Human reproduction open, 2025(3), hoaf025. https://doi.org/10.1093/hropen/hoaf025
Becker, C. M., Johnson, N. P., As-Sanie, S., Arjona Ferreira, J. C., Abrao, M. S., Wilk, K., Imm, S. J., Mathur, V., Perry, J. S., Wagman, R. B., & Giudice, L. C. (2024). Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. Human reproduction (Oxford, England), 39(3), 526–537. https://doi.org/10.1093/humrep/dead263
Pundir, J., Omanwa, K., Kovoor, E., Pundir, V., Lancaster, G., & Barton-Smith, P. (2017). Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An Updated Systematic Review and Meta-analysis. Journal of minimally invasive gynecology, 24(5), 747–756. https://doi.org/10.1016/j.jmig.2017.04.008
Burks, C., Lee, M., DeSarno, M., Findley, J., & Flyckt, R. (2021). Excision versus Ablation for Management of Minimal to Mild Endometriosis: A Systematic Review and Meta-analysis. Journal of minimally invasive gynecology, 28(3), 587–597. https://doi.org/10.1016/j.jmig.2020.11.028
Hashemi, M., Rouholamin, S., Ghahiri, A., & Momeni Alkami, F. (2023). Comparison of laparoscopic ablation versus excision for superficial endometriosis-associated pain. American Journal of Clinical and Experimental Obstetrics & Gynecology, 9(1), 1-7. https://e-century.us/files/ajceog/9/1/ajceog0148677.pdf
Wattanayingcharoenchai, R., Rattanasiri, S., Charakorn, C., Attia, J., & Thakkinstian, A. (2021). Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis. BJOG : an international journal of obstetrics and gynaecology, 128(1), 25–35. https://doi.org/10.1111/1471-0528.16366
Xiong, Y., Huang, W., Wang, C., Ma, W., Jin, S., Lin, J., Deng, X., Peng, Y., Huang, Y., Du, X., & Han, X. (2025). Effectiveness and Safety of Postoperative Medical Treatments Following Fertility-Preserving Surgery for Endometriosis: A Network Meta-Analysis. BJOG : an international journal of obstetrics and gynaecology, 10.1111/1471-0528.70016. Advance online publication. https://doi.org/10.1111/1471-0528.70016
Skhirtladze, D., Kristesashvili, J., & Charekishvili, R. (2024). Efficacy of postsurgical medical therapy for infertile patients with deep endometriosis. Ginekologia polska, 10.5603/gpl.99414. Advance online publication. https://doi.org/10.5603/gpl.99414
Chen, I., Veth, V. B., Choudhry, A. J., Murji, A., Zakhari, A., Black, A. Y., Agarpao, C., & Maas, J. W. (2020). Pre- and postsurgical medical therapy for endometriosis surgery. The Cochrane database of systematic reviews, 11(11), CD003678. https://doi.org/10.1002/14651858.CD003678.pub3
Jiang, D., Zhang, X., Shi, J., Tao, D., & Nie, X. (2021). Risk factors for ovarian endometrioma recurrence following surgical excision: a systematic review and meta‑analysis. Archives of gynecology and obstetrics, 304(3), 589–598. https://doi.org/10.1007/s00404-021-06129-0
Veth, V. B., Keukens, A., Reijs, A., Bongers, M. Y., Mijatovic, V., Coppus, S. F. P. J., & Maas, J. W. M. (2024). Recurrence after surgery for endometrioma: a systematic review and meta-analyses. Fertility and sterility, 122(6), 1079–1093. https://doi.org/10.1016/j.fertnstert.2024.07.033
Keukens, A., Veth, V. B., Regis, M., Mijatovic, V., Bongers, M. Y., Coppus, S. F. P. J., & Maas, J. W. M. (2024). The effect of surgery or medication on pain and quality of life in women with endometrioma. A systematic review and meta-analysis. European journal of obstetrics, gynecology, and reproductive biology, 293, 95–105. https://doi.org/10.1016/j.ejogrb.2023.12.012
Hodgson, R. M., Lee, H. L., Wang, R., Mol, B. W., & Johnson, N. (2020). Interventions for endometriosis-related infertility: a systematic review and network meta-analysis. Fertility and sterility, 113(2), 374–382.e2. https://doi.org/10.1016/j.fertnstert.2019.09.031
Richard, E., Morin, J., Murji, A., Lemyre, M., Laberge, P. Y., & Maheux-Lacroix, S. (2022). Effect of Postoperative Hormonal Suppression on Fertility in Patients With Endometriosis After Conservative Surgery: A Systematic Review and Meta-analysis. Obstetrics and gynecology, 139(6), 1169–1179. https://doi.org/10.1097/AOG.0000000000004811
Desai, J., Strong, S., & Ball, E. (2024). Holistic approaches to living well with endometriosis. F1000Research, 13, 359. https://doi.org/10.12688/f1000research.142586.2
Giese, N., Kwon, K. K., & Armour, M. (2023). Acupuncture for endometriosis: A systematic review and meta-analysis. Integrative medicine research, 12(4), 101003. https://doi.org/10.1016/j.imr.2023.101003
Li, H., Wang, X., Wang, Y., Gao, Y., Zheng, X., Zhang, X., Li, X., Zheng, X., Fan, X., Zuo, G., & She, Y. (2024). Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomized Controlled Trials. Journal of pain research, 17, 3197–3216. https://doi.org/10.2147/JPR.S488343
Chen, C., Li, X., Lu, S., Yang, J., & Liu, Y. (2024). Acupuncture for clinical improvement of endometriosis-related pain: a systematic review and meta-analysis. Archives of gynecology and obstetrics, 310(4), 2101–2114. https://doi.org/10.1007/s00404-024-07675-z
Xie, M., Qing, X., Huang, H., Zhang, L., Tu, Q., Guo, H., & Zhang, J. (2025). The effectiveness and safety of physical activity and exercise on women with endometriosis: A systematic review and meta-analysis. PloS one, 20(2), e0317820. https://doi.org/10.1371/journal.pone.0317820
Can, G., Amorim das Virgens, I. P., Fehér, B., Orbán, E. P., Fehérvári, P., Bánhidy, F., Hegyi, P., Mayer, Á. A., & Ács, N. (2025). Physiotherapy for endometriosis-associated pelvic pain: A systematic review and meta-analysis. Pain medicine (Malden, Mass.), pnaf083. Advance online publication. https://doi.org/10.1093/pm/pnaf083
Mick, I., Freger, S. M., van Keizerswaard, J., Gholiof, M., & Leonardi, M. (2024). Comprehensive endometriosis care: a modern multimodal approach for the treatment of pelvic pain and endometriosis. Therapeutic advances in reproductive health, 18, 26334941241277759. https://doi.org/10.1177/26334941241277759
Fang, Q. Y., Campbell, N., Mooney, S. S., Holdsworth-Carson, S. J., & Tyson, K. (2024). Evidence for the role of multidisciplinary team care in people with pelvic pain and endometriosis: A systematic review. The Australian & New Zealand journal of obstetrics & gynaecology, 64(3), 181–192. https://doi.org/10.1111/ajo.13755
McReynolds, D., Shiraz, R., Tangey, M. A., Egerton, T., & Frawley, H. (2025). Effectiveness of Multidisciplinary Treatment Compared to Single Discipline Treatment of Female Chronic Pelvic Pain: A Systematic Review and Meta-Analyses. BJOG : an international journal of obstetrics and gynaecology, 132(12), 1716–1733. https://doi.org/10.1111/1471-0528.18322
Qu, H., Du, Y., Yu, Y., Wang, M., Han, T., & Yan, L. (2022). The effect of endometriosis on IVF/ICSI and perinatal outcome: A systematic review and meta-analysis. Journal of gynecology obstetrics and human reproduction, 51(9), 102446. https://doi.org/10.1016/j.jogoh.2022.102446
Latif, S., Khanjani, S., & Saridogan, E. (2024). Endometriosis and In Vitro Fertilization. Medicina (Kaunas, Lithuania), 60(8), 1358. https://doi.org/10.3390/medicina60081358
Alson, S., Henic, E., Jokubkiene, L., & Sladkevicius, P. (2024). Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment. Fertility and sterility, 121(5), 832–841. https://doi.org/10.1016/j.fertnstert.2024.01.023
Becker, C. M., Bokor, A., Heikinheimo, O., Horne, A., Jansen, F., Kiesel, L., King, K., Kvaskoff, M., Nap, A., Petersen, K., Saridogan, E., Tomassetti, C., van Hanegem, N., Vulliemoz, N., Vermeulen, N., & ESHRE Endometriosis Guideline Group (2022). ESHRE guideline: endometriosis. Human reproduction open, 2022(2), hoac009. https://doi.org/10.1093/hropen/hoac009
Younis, J. S., & Taylor, H. S. (2024). The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews. Frontiers in endocrinology, 15, 1397279. https://doi.org/10.3389/fendo.2024.1397279
Wu, C. Q., Albert, A., Alfaraj, S., Taskin, O., Alkusayer, G. M., Havelock, J., Yong, P., Allaire, C., & Bedaiwy, M. A. (2019). Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses. Journal of minimally invasive gynecology, 26(2), 299–311.e3. https://doi.org/10.1016/j.jmig.2018.08.029
Colombi, I., Ginetti, A., Cannoni, A., Cimino, G., d'Abate, C., Schettini, G., Giorgi, M., Raimondo, D., Martire, F. G., Lazzeri, L., Zupi, E., & Centini, G. (2024). Combine Surgery and In Vitro Fertilization (IVF) in Endometriosis-Related Infertility: When and Why. Journal of clinical medicine, 13(23), 7349. https://doi.org/10.3390/jcm13237349
Riemma, G. (2025). Surgery prior to IVF/ICSI versus up-front IVF/ICSI for the treatment of infertility associated with ovarian and deep infiltrating endometriosis: A systematic review and meta-analysis. Reproductive BioMedicine Online, Article 105178. https://doi.org/10.1016/j.rbmo.2025.105178
Bourdon, M., Peigné, M., Maignien, C., de Villardi de Montlaur, D., Solignac, C., Darné, B., Languille, S., Bendifallah, S., & Santulli, P. (2024). Impact of Endometriosis Surgery on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes: a Systematic Review and Meta-analysis. Reproductive sciences (Thousand Oaks, Calif.), 31(6), 1431–1455. https://doi.org/10.1007/s43032-023-01421-7
Shao, W., Li, Y., & Wang, Y. (2023). Impact of dienogest pretreatment on IVF-ET outcomes in patients with endometriosis: a systematic review and meta-analysis. Journal of ovarian research, 16(1), 166. https://doi.org/10.1186/s13048-023-01245-8
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