Should patients undergo endometrioma surgery before IVF/ICSI? a retrospective study with propensity score matching

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Abstract

RESEARCH QUESTION: Does surgical management of ovarian endometriomas improve in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)? DESIGN: This retrospective study analyzed 1,456 IVF/ICSI cycles from June 2017 to September 2022, comparing 530 control cycles with 926 endometriosis (EMS) cycles. The EMS group comprised pre-EMS (non-operated endometriomas, N = 272) and post-EMS (operated endometriomas, N = 654) subgroups. Propensity score matching (PSM) balanced female age, antral follicle count (AFC), body mass index (BMI), anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol levels. Receiver operating characteristic (ROC) analyses identified potential predictors of high-quality D3 embryos and live birth. RESULTS: After PSM, the EMS group showed significantly lower normal fertilization rates, D3 embryo rates, and ovarian sensitivity index (OSI) compared to the control group (P < 0.05), but comparable oocyte yield, fertilization outcomes, and embryo parameters. Subgroup analysis showed that advanced-stage post-EMS cases had fewer retrieved oocytes and embryos, along with lower OSI, than the pre-EMS group after PSM. LBRs were similar between the EMS and control groups, irrespective of prior endometrioma surgery. ROC analysis identified AMH (cutoff 1.17 ng/mL; AUC 0.703, 95% CI 0.654-0.752) and AFC (cutoff 7.5; AUC 0.670, 95% CI 0.621-0.720) as predictors of high-quality day-3 embryos in EMS patients. In post-EMS patients, AMH (cutoff value 1.175; AUC 0.703, 95% CI 0.647-0.759) and AFC (cutoff 6.5; AUC 0.667, 95% CI 0.608-0.725) were predictive. AMH, AFC, age, and endometrioma size did not predict live birth. CONCLUSION: Advanced-stage Endometriosis negatively impacts oocyte quantity and ovarian response, but endometrioma surgery may not improve these outcomes or LBRs. Following exclusion of malignancy, asymptomatic endometriosis patients with AMH ≤ 1.17 ng/mL or AFC ≤ 7 should not routinely undergo cystectomy.
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Results

PSM effectively balanced covariates, as shown in Tables 1 , 2 , 3 and 4 . No significant differences remained in female age or BMI after PSM1, or in female age, BMI, AMH, AFC, FSH, or E2 after PSM2 (all P  > 0.05), confirming adequate cohort matching ( P  > 0.05). Table 1 Baseline characteristics and oocyte aspiration characteristics in the control group and endometriosis group after propensity score matching PSM1 PSM2 CON group EMS group P CON group EMS group P No. of oocyte aspiration cycles, n 490 490 390 390 EMS phenotypes, n (%)  Endometrioma 135(27.5) 124(31.8)  Stage I-II 112(22.9) 98(25.1)  Stage III-IV 243(49.6) 168(43.1) Diameters of the biggest endometrioma, mm  Pre-EMS group 25.0(19.2-34.1) 23.9(18.9-31.0)  Post-EMS group 39.0(20.7-56.0) 36.7(12.5-52.7) Female age (y) 30(28-34) 30(28-34) 0.821 31.0(28.0-34.5) 31.0(28.0-34.0) 0.800 BMI (kg/m 2 ) 21.2(19.5-23.4) 21.0(19.2-22.9) 0.225 21.2(19.4-23.4) 20.9(19.3-23.0) 0.387 Duration of female infertility (y) 3.0(2.0-5.0) 3.0(2.0-4.0) <0.001 3.0(2.0-5.0) 3.0(2.0-4.0) <0.001 Primary infertility, n (%) 325(66.3) 282(57.6) 0.005 249(63.8) 223(57.2) 0.057 AFC 15.5(11.0-20.0) 10.0(6.0-15.0) <0.001 14.0(11.0-18.0) 13.0(9.0-18.0) 0.409 AMH (ng/mL) 3.6(2.4-5.2) 1.9(0.8-3.6) <0.001 3.2(2.1-4.6) 2.9(1.7-4.9) 0.085 Basic hormone (D2-D5 of menstruation)  LH (IU/L) 3.7(2.6-5.5) 4.3(3.0-5.8) 0.003 3.8(2.6-5.5) 3.9(2.7-5.4) 0.660  FSH (IU/L) 6.8(4.8-8.4) 7.6(6.0-9.6) <0.001 7.1(4.9-8.7) 7.0(5.6-8.2) 0.725  E2 (pmol/L) 127.3(92.8-167.9) 167.2(118.3-248.0) <0.001 131.0(93.0-172.0) 133.0(95.2-184.3) 0.517 Menstruation (d) 29.0(29.0-31.1) 27.0(29.0-29.0) <0.001 29.0(29.0-31.8) 29.0(28.5-29.0) <0.001 Gonadotrophin dosage (IU) 1725.0(1350.0-2225.0) 2025.0(1525.0-2800.0) <0.001 1825.0(1375.0-2306.3) 1925.0(1500.0-2581.3) 0.010 Gonadotrophin duration (d) 10.0(9.0-11.0) 10.0(9.0-12.0) 0.053 10.0(9.0-11.0) 10.0(9.0-12.0) 0.494 Male age (y) 33.0(30.0-36.0) 32.0(30.0-35.0) 0.057 33.0(30.0-37.0) 32.5(30.0-36.0) 0.121 Hormones on trigger day  E2 (pmol/L) 10147.0(6939.0-15609.0) 7683.0(4204.0-13285.0) <0.001 9670.0(6436.0-15264.0) 9530.0(6088.8-15719.8) 0.512  P (nmol/L) 3.3(2.4-4.3) 3.2(2.2-4.4) 0.400 3.2(2.4-4.4) 3.1(2.2-4.5) 0.574  LH (IU/L) 2.0(1.3-2.9) 2.2(1.3-4.1) 0.006 2.0(1.4-2.9) 1.8(1.2-2.7) 0.041  FSH (IU/L) 13.9(10.8-18.4) 17.0(13.0-23.9) <0.001 14.6(11.1-19.2) 15.1(11.9-20.4) 0.059 No. of retrieved oocytes, n 13.0(9.0-18.0) 8.0(4.0-14.0) <0.001 12.0(9.0-17.0) 11.0(7.0-16.3) 0.151 No. of retrieved MII oocytes, n 11.0(7.0-15.0) 8.0(4.0-12.0) <0.001 10.0(7.0-14.0) 9.0(6.0-14.0) 0.661 Method of insemination, % (n) <0.001 <0.001  IVF 19.6(96) 66.9(328) 17.2(67) 71.5(279)  ICSI 68.2(334) 28.0(137) 71.3(278) 20.8(81)  IVF/ICSI 12.2(60) 5.1(25) 11.5(45) 7.7(30) Protocols, % (n) <0.001 0.006  GnRH-a 53.5(262) 43.9(215) 62.1(242) 55.9(218)  GnRH-A 40.0(196) 24.7(121) 31.0(121) 30.3(118)  others 6.5(32) 31.4(154) 6.9(27) 13.8(54) No. of total fertilized oocytes, n 8.0(5.0-12.0) 6.0(3.0-10.0) <0.001 8.0(5.0-12.0) 8.0(5.0-12.3) 0.249 No. of normal fertilized oocytes, n 8.0(5.0-12.0) 5.0(2.0-9.0) <0.001 7.0(4.0-11.0) 7.0(4.0-11.0) 0.285 No. of abnormal fertilized oocytes, n 0.0(0.0-1.0) 0.0(0.0-1.0) 0.014 0.0(0.0-1.0) 1.0(0.0-2.0) <0.001 No. of cleavage embryos, n 7.0(5.0-11.0) 5.0(2.0-9.0) <0.001 7.0(4.0-11.0) 7.0(4.0-10.0) 0.312 No. of D3 embryos, n 8.0(5.0-11.0) 5.0(2.0-9.0) <0.001 7.0(4.0-11.0) 7.0(4.0-10.0) 0.337 No. of top-quality D3 embryos, n 3.0(2.0-6.0) 2.0(1.0-5.0) <0.001 3.0(2.0-5.0) 3.0(1.0-5.0) 0.123 No. of blastocyst culture cycles, n (%) 394.0(80.4) 320(65.3) <0.001 301.0(77.2) 313.0(80.3) 0.294 No. of D3 embryos in blastocyst culture, n 4.0(2.0-8.0) 2.0(0.0-5.0) <0.001 1.0(4.0-7.0) 1.0(4.0-7.0) 0.884 No. of viable blastocyst, n 1.0(0.0-3.0) 0.0(0.0-2.0) <0.001 1.0(0.0-3.0) 1.0(0.0-2.0) 0.912 OSI 7.3(4.3-11.4) 3.8(2.0-7.5) <0.001 6.7(3.9-10.0) 5.4(3.1-9.8) 0.014 Oocyte maturation rate, % 84.6(75.0-95.1) 90.7(80.0-100.0) <0.001 84.6(75.0-97.3) 88.9(79.3-100.0) 0.001 Total Fertilization rate, % 66.7(52.8-80.2) 75.0(55.6-91.4) <0.001 66.7(52.0-83.3) 77.8(60.0-90.2) <0.001 Normal fertilization rate, % 58.3(44.4-72.2) 55.6(35.2-76.3) 0.387 60.0(44.4-75.0) 50.0(36.6-70.0) <0.001 D3 rate, % 100.0(84.6-100.0) 88.9(71.4-100.0) <0.001 100.0(84.6-100.0) 87.5(75.0-100.0) <0.001 High-quality D3 rate, % 50.0(30.0-66.7) 50.0(16.7-66.7) 0.123 50.0(28.6-66.7) 50.0(25.0-66.7) 0.402 Blastocyst rate, % 33.3(0.0-50.0) 26.1(0.0-50) 0.251 25.0(0.0-50.0) 25.0(0.0-50.0) 0.995 Values are expressed as n (%), percentage (%) or median (upper and lower quartile). The bold number highlights the p which was less than 0.05 EMS Endometriosis group (including endometrioma with surgery or without surgery), CON The control group, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of oocytes were fertilized via IVF, and half of oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Table 2 Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups after propensity score matching PSM1 PSM2 Pre-EMS group Post-EMS group P Pre-EMS group Post-EMS group P No. of oocyte aspiration cycles, n 272 272 224 224 EMS phenotypes, n (%)  Endometrioma 272 (100) 224 (100)  Stage I-II 78(28.7) 81(36.2)  Stage III-IV 194(71.3) 143(63.8) Diameters of the biggest endometrioma, mm 24.3(19.3-31.3) 40.0(23.3-54.7) <0.001 24.2(19.0-32.1) 36.7(10.0-53.5) <0.001 Female age (y) 32.0(29.0-36.0) 33.0(30.0-36.0) 0.309 33.0(29.0-37.0) 33.0(30.0-36.0) 0.803 BMI (kg/m 2 ) 20.5(18.8-22.4) 21.1(19.5-22.5) 0.113 20.7(18.8-22.6) 20.8(19.5-22.7) 0.477 Duration of female infertility (y) 3.0(2.0-4.0) 3.0(2.0-5.0) 0.182 3.0(2.0-4.0) 3.0(2.0-4.8) 0.429 Primary infertility, n(%) 153(56.3) 134(49.3) 0.103 125(55.8) 97(43.3) 0.008 AFC 11.0(7.0-16.0) 9.0(5.3-14.0) <0.001 10.0(7.0-15.0) 10.0(6.0-15.8) 0.385 AMH (ng/mL) 2.9(1.3-4.7) 1.6(0.6-2.9) <0.001 2.3(1.2-4.1) 2.2(1.0-4.1) 0.563 Basic hormone (D2-D5 of menstruation)  LH (IU/L) 4.9(3.5-6.7) 4.3(3.0-5.9) <0.001 4.8(3.4-6.4) 4.0(2.9-5.8) 0.002  FSH (IU/L) 7.9(6.5-10.0) 8.0(6.4-11.1) 0.210 8.0(6.6-10.7) 7.6(6.1-10.1) 0.119  E2 (pmol/L) 168.4(109.0-248.8) 158.6(110.5-221.0) 0.162 168.2(109.8-235.2) 166.9(124.0-233.0) 0.424 Menstruation (d) 29.0(28.5-29.0) 29.0(27.1-29.0) 0.005 29.0(28.0-29.0) 29.0(27.5-29.0) 0.294 Gn dosage (IU) 2000.0(1575.0-2625.0) 2025.0(1459.4-2859.4) 0.858 2062.5(1575.0-2718.8) 1875.0(1369.4-2543.8) 0.015 Gn duration (d) 10.0(9.0-12.0) 10.0(8.3-12.0) 0.129 10.0(9.0-12.0) 10.0(9.0-11.0) 0.016 Male age (y) 34.0(30.0-39.0) 34.0(31.0-37.8) 0.640 35.0(30.0-39.0) 34.0(31.0-38.0) 0.561 Hormones on trigger day  E2 (pmol/L) 10019.0(6180.5-15596.3) 6698.0(3550.5-11103.0) <0.001 9138.0(5798.5-13237.5) 7285.0(4811.5-14007.8) 0.116  P (nmol/L) 3.0(2.1-4.6) 3.1(2.1-4.6) 0.974 2.9(2.1-4.0) 3.1(2.1-4.6) 0.185  LH (IU/L) 1.8(1.2-3.0) 2.6(1.5-4.4) <0.001 1.8(1.2-3.1) 2.2(1.3-3.6) 0.068  FSH (IU/L) 15.9(12.6-22.2) 17.6(13.4-25.1) 0.006 16.6(12.7-22.3) 16.4(12.5-24.3) 0.542 No. of retrieved oocytes, n 11.0(6.0-16.0) 7.0(3.0-12.0) <0.001 10.0(5.3-15.0) 8.0(4.0-14.0) 0.098 No. of retrieved MII oocytes, n 9.0(5.0-14.0) 6.0(3.0-10.0) <0.001 9.0(4.0-13.0) 7.0(3.0-12.0) 0.071 Method of insemination, % (n) 0.065 0.170  IVF 66.2(180) 58.5(159) 68.3(153) 61.2(137)  ICSI 26.1(71) 35.3(96) 24.6(55) 32.6(73)  IVF/ICSI 7.7(21) 6.3(17) 7.1(16) 6.3(14) Protocols, %(n) <0.001 0.774  GnRH-a 45.6(124) 40.8(111) 46.0(103) 46.4(104)  GnRH-A 30.1(82) 20.2(55) 28.1(63) 25.4(57)  others 24.3(66) 39(106) 25.9(58) 28.1(63) No. of total fertilized oocytes, n 8.0(4.0-12.0) 5.0(2.0-8.0) <0.001 7.0(3.0-10.0) 6.0(2.0-11.0) 0.093 No. of normal fertilized oocytes, n 6.0(3.0-10.0) 4.0(2.0-7.0) <0.001 6.0(3.0-8.0) 5.0(2.0-9.0) 0.114 No. of abnormal fertilized oocytes, n 1.0(0.0-2.0) 0.0(0.0-1.0) 0.001 1.0(0.0-2.0) 0.0(0.0-2.0) 0.132 No. of cleavage embryos, n 6.0(3.0-9.0) 4.0(2.0-7.0) <0.001 6.0(3.0-8.0) 5.0(2.0-9.0) 0.106 No. of D3 embryos, n 6.0(3.0-10.0) 4.0(2.0-7.0) <0.001 6.0(3.0-9.0) 5.0(2.0-9.0) 0.091 No. of top-quality D3 embryos, n 3.0(1.0-5.0) 2.0(1.0-3.0) <0.001 3.0(1.0-5.0) 2.0(1.0-4.0) 0.042 No. of blastocyst culture cycles, n (%) 198(72.8) 158(58.1) <0.001 156(69.6) 142(63.4) 0.161 No. of embryos in blastocyst culturation, n 3.0(0.0-7.0) 1.0(0.0-4.0) <0.001 3.0(0.0-6.0) 2.0(0.0-5.0) 0.236 No. of viable blastocyst, n 0.0(0.0-2.0) 0.0(0.0-1.0) <0.001 0.0(0.0-2.0) 0.0(0.0-1.0) 0.054 OSI 4.8(2.6-8.7) 3.2(1.6-5.8) <0.001 4.4(2.4-7.3) 4.1(1.8-7.9) 0.427 Oocyte maturation rate, % 90.0(79.1-100.0) 94.4(81.8-100.0) 0.054 91.1(80.0-100.0) 93.3(80.0-100.0) 0.970 Total Fertilization rate, % 75.0(60.0-90.0) 79.5(61.5-100.0) 0.292 75.0(60.0-90.2) 75.0(57.1-91.3) 0.338 Normal fertilization rate, % 55.2(35.7-73.5) 57.1(38.0-83.6) 0.358 55.4(35.3-74.2) 50.0(35.9-75.0) 0.539 D3 rate, % 88.9(75.0-100.0) 90.9(66.7-100.0) 0.532 87.9(75.0-100.0) 87.5(70.0-100.0) 0.345 High-quality D3 rate, % 50.0(25.0-71.4) 50.0(20.0-71.4) 0.319 50.0(25.0-72.3) 50.0(21.1-71.4) 0.317 Blastocyst Rate, % 33.3(0.0-50.0) 20.0(0.0-51.5) 0.292 33.3(0.0-50.0) 12.5(0.0-42.9) 0.092 Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AM , Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Table 3 Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups at stage I/II stage after propensity score matching PSM1 PSM2 Pre-EMS group Post-EMS I/II group P1 Pre-EMS group Post-EMS I/II group P1 No. of oocyte aspiration cycles 201 201 158 158 Diameters of the biggest endometrioma, mm 24.0(19.0-31.0) 15.0(0.0-35.0) <0.001 24.0(18.5-31.33) 15.0(0.0-35.0) <0.001 Female age (y) 33.0(29.0-36.0) 33.0(30.0-36.0) 0.535 33.5(29.8-37.0) 33.0(30.0-36.3) 0.850 BMI (kg/m 2 ) 20.7(19.1-22.5) 21.0(19.6-23.0) 0.135 21.2(19.3-22.9) 21.1(19.6-23.3) 0.504 Duration of female infertility (y) 3.0(2.0-4.0) 3.0(2.0-4.0) 0.508 3.0(1.8-4.0) 3.0(2.0-4.0) 0.207 Primary infertility, n (%) 109(54.2) 95(47.3) 0.163 78(49.4) 73(46.2) 0.573 AFC 10.0(7.0-16.0) 10.0(6.0-15.0) 0.137 10.0(6.0-14.3) 10.0(5.0-14.0) 0.632 AMH (ng/mL) 2.6(1.2-4.5) 1.7(0.7-3.2) <0.001 1.9(1.0-3.5) 1.9(0.8-3.6) 0.596 Basic hormone (D3-D5 of menstruation)  LH (IU/L) 4.9(3.5-6.6) 3.7(3.0-5.4) <0.001 5.0(3.3-6.4) 3.8(3.2-5.3) <0.001  FSH (IU/L) 7.9(6.5-10.4) 7.9(6.5-10.3) 0.970 8.1(6.6-10.9) 8.0(6.6-11.0) 0.696  E2 (pmol/L) 163.5(104.8-235.9) 157.0(110.6-219.5) 0.616 167.7(103.8-235.1) 161.0(111.8-222.8) 0.903 Menstruation cycles (d) 29.0(28.0-29.0) 29.0(27.5-29.0) 0.026 29.0(27.0-29.0) 29.0(27.5-29.0) 0.809 Gn dosage (IU) 2025.0(1575.0-2650.0) 1800.0(1350.0-2725.0) 0.024 2100.0(1643.8-2925.0) 1800.0(1350.0-2556.3) 0.002 Gn duration (d) 10.0(9.0-12.0) 10.0(8.0-11.0) <0.001 11.0(9.0-12.0) 9.5(8.0-12.0) <0.001 Male age (y) 35.0(30.0-39.0) 34.0(31.0-38.0) 0.511 35.0(30.0-40.0) 34.0(30.0-38.0) 0.155 Hormones on trigger day  E2 (pmol/L) 9976.5(5863.3-15488.3) 6683.0(4118.0-11241.0) <0.001 9175.0(5632.5-13003.5) 6668.0(4136.8-11696.5) 0.026  P (nmol/L) 3.0(2.1-4.3) 3.1(2.1-4.4) 0.720 2.9(2.1-4.1) 3.0(2.1-4.3) 0.639  LH (IU/L) 1.8(1.3-3.2) 2.3(1.4-3.8) 0.081 1.8(1.3-3.3) 2.2(1.3-3.7) 0.164  FSH (IU/L) 16.3(12.6-23.0) 17.4(13.4-24.3) 0.158 17.2(12.9-24.1) 17.3(13.4-25.5) 0.601 No. of retrieved oocytes, n 10.0(5.5-15.0) 8.0(4.0-13.0) 0.009 9.0(4.0-14.0) 8.0(4.0-13.0) 0.586 No. of retrieved MII oocytes, n 9.0(4.0-14.0) 7.0(3.0-11.0) 0.007 8.0(4.0-11.0) 7.0(3.0-11.0) 0.497 Method of insemination, % (n) <0.001 0.092  IVF 85.1(171) 68.7(138) 78.5(124) 67.7(107)  ICSI 14.4(29) 26.4(53) 18.4(29) 26.6(42)  IVF/ICSI 0.5(1) 5.0(10) 3.2(5) 5.7(9) Protocols, % (n) 0.028 0.181  GnRH-a 47.3(95) 42.3(85) 49.4(78) 41.1(65)  GnRH-A 26.9(54) 19.9(40) 22.8(36) 21.5(34)  others 25.9(52) 37.8(76) 27.8(44) 37.3(59) No. of total fertilized oocytes, n 8.0(3.5-11.0) 6.0(3.0-9.5) 0.008 6.0(3.0-10.0) 6.0(3.0-10.0) 0.483 No. of normal fertilized oocytes, n 6.0(3.0-9.0) 5.0(2.0-8.0) 0.010 6.0(3.0-8.0) 5.0(2.8-8.0) 0.503 No. of abnormal fertilized oocytes, n 1.0(0.0-2.0) 0.0(0.0-1.5) 0.020 1.0(0.0-2.0) 0.0(0.0-1.3) 0.548 No. of cleavage embryos, n 6.0(3.0-9.0) 5.0(2.0-8.0) 0.007 5.0(3.0-8.0) 5.0(2.0-8.0) 0.441 No. of D3 embryos, n 6.0(3.0-10.0) 5.0(2.0-8.0) 0.006 5.0(3.0-8.0) 5.0(2.0-8.0) 0.412 No. of top-quality D3 embryos, n 3.0(1.0-5.0) 2.0(1.0-4.0) 0.020 3.0(1.0-4.3) 2.0(1.0-4.0) 0.260 No. of blastocyst culture cycles, n (%) 142(70.6) 131(65.2) 0.240 104(65.8) 104(65.8) 1.000 No. of embryos in blastocyst culturation, n 2.0(0.0-6.0) 2.0(0.0-5.0) 0.048 2.0(0.0-5.0) 2.0(0.0-5.0) 0.968 No. of viable blastocysts, n 0.0(0.0-2.0) 0.0(0.0-1.0) 0.058 0.0(0.0-2.0) 0.0(0.0-2.0) 0.908 OSI index 4.6(2.4-7.8) 3.7(2.0-6.9) 0.161 3.7(1.7-6.5) 4.1(2.2-8.0) 0.321 Oocyte maturation rate, % 92.9(80.0-100.0) 91.7(80.0-100.0) 0.601 93.8(82.9-100.0) 91.7(79.2-100.0) 0.222 Total Fertilization rate, % 80.0(60.6-93.2) 75.0(58.3-100.0) 0.129 80.0(60.0-93.5) 75.0(58.8-93.8) 0.192 Normal fertilization rate, % 55.6(36.6-75.0) 50.0(33.3-75.0) 0.423 57.1(33.3-75.3) 50.0(33.3-72.7) 0.345 D3 rate, % 87.5(73.3-100.0) 87.5(71.4-100.0) 0.622 87.5(71.1-100.0) 88.9(75.0-100.0) 0.901 High-quality D3 rate, % 50.0(25.0-73.7) 50.0(10.0-69.2) 0.177 50.0(25.0-73.1) 50.0(16.7-69.2) 0.139 Blastocyst rate, % 26.1(0.0-50.0) 20.0(0.0-57.1) 0.824 25.0(0.0-50.0) 25.0(0.0-60.0) 0.467 Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS I/II group Endometriosis at the stage I/II after operation, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Table 4 Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups at EMS III/IV stage after propensity score matching PSM1 PSM2 Pre-EMS Post-EMS III/IV P1 Pre-EMS Post-EMS III/IV P1 No. of oocyte aspiration cycles 271 271 198 198 Diameters of the biggest endometrioma, mm 24.3(19.3-31.5) 44.3(30.0-56.2) <0.001 24.0(19.3-31.7) 46.7(33.5) <0.001 Female age (y) 32.0(29.0-36.0) 33.0(30.0-36.0) 0.783 33.0(29.0-37.0) 33.0(30.0-36.0) 0.709 BMI (kg/m 2 ) 20.4(18.8-22.3) 20.7(19.0-22.6) 0.705 20.7(18.8-22.7) 20.8(19.2-22.5) 0.865 Duration of female infertility (y) 3.0(2.0-4.0) 3.0(1.9-5.0) 0.547 3.0(2.0-4.0) 3.0(2.0-5.0) 0.023 Primary infertility, n(%) 152(56.1) 133(49.1) 0.102 106(53.8) 86(43.7) 0.044 AFC 11.0(7.0-15.0) 8.0(5.0-12.5) <0.001 10.0(6.0-14.0) 9.0(6.0-14.0) 0.228 AMH (ng/mL) 2.8(1.2-4.7) 1.5(0.5-2.6) <0.001 2.0(1.0-3.6) 2.0(0.8-3.4) 0.474 Basic hormone (D3-D5 of menstruation)  LH (IU/L) 4.9(3.5-6.7) 4.3(2.7-5.9) 0.001 4.8(3.3-6.2) 4.5(2.9-6.1) 0.011  FSH (IU/L) 7.9(6.5-9.9) 8.0(6.2-11.2) 0.418 8.1(6.7-10.9) 7.9(6.2-10.8) 0.298  E2 (pmol/L) 167.5(107.0-241.5) 153.1(109.7-222.1) 0.307 169.0(112.7-237.0) 162.3(112.0-235.0) 0.764 Menstruation cycles (d) 29.0(28.4-29.0) 29.0(27.0-29.0) 0.001 29.0(27.3-29.0) 29.0(27.5-29.0) 0.955 Gn dosage (IU) 2000.0(1575.0-2625.0) 2100.0(1575.0-3025.0) 0.149 2100.0(1668.8-2925.0) 2070.0(1603.1-2925.0) 0.940 Gn duration (d) 10.0(9.0-12.0) 10.0(9.0-12.0) 0.549 10.5(9.0-12.0) 10.0(9.0-12.0) 0.664 Male age (y) 34.0(30.0-39.0) 34.0(31.0-37.0) 0.352 35.0(30.0-39.0) 35.0(31.5-38.0) 0.668 Hormones on trigger day  E2 (pmol/L) 10035.0(6168.0-15626.5) 6446.0(3164.3-12524.8) <0.001 8757.5(5657.0-12696.8) 7134.5(3889.5-12701.5) 0.019  P (nmol/L) 3.0(2.1-4.6) 3.0(2.0-4.4) 0.817 2.9(2.0-4.1) 3.2(2.2-4.9) 0.068  LH (IU/L) 1.8(1.2-3.0) 2.3(1.4-4.4) <0.001 1.8(1.2-3.4) 2.2(1.4-4.4) 0.011  FSH (IU/L) 16.0(12.6-22.2) 19.2(14.3-27.9) <0.001 17.4(13.4-23.0) 18.4(13.0-25.2) 0.304 No. of retrieved oocytes, n 10.0(6.0-16.0) 6.0(3.0-11.0) <0.001 9.0(4.5-14.0) 7.0(3.0-13.0) 0.021 No. of retrieved MII oocytes, n 9.0(4.0-14.0) 5.0(2.0-10.0) <0.001 8.0(4.0-13.0) 6.0(2.5-11.5) 0.019 Method of insemination, % (n) 0.011 0.758  IVF 66.4(180) 60.5(164) 67.5(133) 65.5(129)  ICSI 25.8(70) 35.8(97) 25.4(50) 28.4(56)  IVF/ICSI 7.7(21) 3.7(10) 7.1(14) 6.1(12) Protocols, % (n) <0.001 0.736  GnRH-a 45.8(124) 41.3(112) 46.2(91) 43.1(85)  GnRH-A 29.9(81) 19.6(53) 24.4(48) 23.9(47)  others 24.4(66) 39.1(106) 29.4(58) 33.0(65) No. of total fertilized oocytes, n 8.0(4.0-11.0) 4.0(2.0-8.0) <0.001 6.0(3.0-10.0) 5.0(2.0-10.0) 0.044 No. of normal fertilized oocytes, n 6.0(3.0-9.0) 4.0(1.0-7.0) <0.001 5.0(3.0-8.0) 4.0(2.0-8.0) 0.038 No. of abnormal fertilized oocytes, n 1.0(0.0-2.0) 0.0(0.0-1.0) <0.001 1.0(0.0-2.0) 0.0(0.0-1.5) 0.452 No. of cleavage embryos, n 6.0(3.0-9.0) 4.0(1.0-7.0) <0.001 5.0(3.0-8.0) 4.0(2.0-8.0) 0.027 No. of D3 embryos, n 6.0(3.0-10.0) 4.0(2.0-7.0) <0.001 5.0(3.0-9.0) 4.0(2.0-8.0) 0.013 No. of top-quality D3 embryos, n 3.0(1.0-5.0) 1.0(0.0-3.0) <0.001 2.0(1.0-5.0) 2.0(1.0-4.0) 0.006 No. of blastocyst culture cycles, n (%) 197(72.7) 148(54.6) <0.001 130(66.0) 122(61.9) 0.401 No. of embryos in blastocyst culturation, n 3.0(0.0-7.0) 1.0(0.0-4.0) <0.001 2.0(0.0-6.0) 2.0(0.0-5.0) 0.237 No. of viable blastocyst, n 0.0(0.0-2.0) 0.0(0.0-1.0) <0.001 0.0(0.0-2.0) 0.0(0.0-1.0) 0.147 OSI 4.8(2.6-8.6) 2.7(1.2-5.2) <0.001 4.0(2.2-6.8) 3.2(1.5-6.2) 0.036 Oocyte maturation rate, % 90.0(79.3-100.0) 100.0(80.0-100.0) 0.059 92.0(80.0-100.0) 93.3(80.0-100.0) 0.582 Total Fertilization rate, % 75.0(60.0-90.0) 79.5(56.7-100.0) 0.940 75.0(57.1-91.3) 80.0(63.9-100.0) 0.489 Normal fertilization rate, % 55.4(35.7-73.6) 57.1(33.3-80.0) 0.967 55.6(35.3-75.0) 55.3(37.0-80.0) 0.781 D3 rate, % 88.9(75.0-100.0) 90.5(66.7-100.0) 0.396 88.9(75.0-100.0) 87.5(67.3-100.0) 0.446 High-quality D3 rate, % 50.0(25.0-71.4) 45.7(0.0-66.7) 0.036 50.0(25.0-72.4) 50.0(20.0-66.7) 0.271 Blastocyst rate, % 33.3(0.0-50.0) 22.5(0.0-50.0) 0.329 29.3(0.0-50.0) 20.0(0.0-50.0) 0.264 Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS III/IV group Endometriosis at the stage III/IV after operation, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Baseline characteristics and oocyte aspiration characteristics in the control group and endometriosis group after propensity score matching Values are expressed as n (%), percentage (%) or median (upper and lower quartile). The bold number highlights the p which was less than 0.05 EMS Endometriosis group (including endometrioma with surgery or without surgery), CON The control group, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of oocytes were fertilized via IVF, and half of oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups after propensity score matching Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AM , Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups at stage I/II stage after propensity score matching Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS I/II group Endometriosis at the stage I/II after operation, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Baseline characteristics and oocyte aspiration characteristics in the non-operated endometrioma and operated endometrioma groups at EMS III/IV stage after propensity score matching Values are expressed as n (%), percentage (%) or median(upper and lower quartile). The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS III/IV group Endometriosis at the stage III/IV after operation, PSM1 Propensity score matching for female age and BMI, PSM2 Propensity score matching for female age, BMI, AMH, AFC, FSH and estradiol, IVF In vitro fertilization, ICSI Intracytoplasmic sperm injection, IVF/ICSI Half of MII oocytes were fertilized via IVF, and half of MII oocytes were fertilized via ICSI, AMH Anti-Müllerian hormone, AFC Antral follicular count, BMI Body mass index, FSH Follicle-stimulating hormone, LH Luteal hormone, E2 Estradiol, P Progesterone, OSI Ovarian sensitivity index, Gn Gonadotropin, GnRH-a Gonadotrophin release hormone agonist, GnRH-A Gonadotrophin release hormone antagonist Table 1 compares baseline characteristics, ovarian response, and embryo quality between the EMS and CON groups following PSM1 and PSM2. After both PSM1 and PSM2, the EMS group demonstrated significantly shorter durations of female infertility and menstrual cycles versus the CON group (all P  < 0.001). Gonadotrophin doses were significantly higher ( P  < 0.001 both), while the OSI was significantly lower (PSM1: P  < 0.001; PSM2: P  = 0.01) in the EMS group compared to controls. Oocyte maturation rates and total fertilization rates were significantly higher in the EMS group after both matchings (all P  < 0.01). Conversely, The D3 rate was significantly lower in the EMS group after both PSM1 and PSM2 ( P   0.05). Following PSM1, the EMS group exhibited significantly fewer retrieved oocytes, metaphase II (MII) oocytes, fertilized oocytes, normally fertilized oocytes, D3 embryos, high-quality D3 embryos, and viable blastocysts (all P  < 0.001). However, these significant differences in embryo/oocyte counts were absent after PSM2.The normal fertilization rate was comparable between groups after PSM1 but significantly lower in the EMS group after PSM2 ( P  < 0.001). Table 2 compares baseline characteristics, ovarian response, and embryo quality between pre-EMS and post-EMS groups after PSM1 and PSM2. Following both PSM methods, the post-EMS group had significantly fewer high-quality D3 embryos and lower basal LH levels than the pre-EMS group (all P  < 0.05). After PSM1, the post-EMS group showed significant reductions in retrieved oocytes, MII oocytes, total fertilized oocytes, normally fertilized oocytes, D3 embryos, and viable blastocysts (all P  < 0.001). Trigger day OSI and E2 levels were also significantly lower, while FSH and LH levels were significantly higher in the post-EMS group (all P   0.05). Gonadotropin dosage and duration were similar between groups after PSM1 ( P  > 0.05), but were significantly lower in the post-EMS group after PSM2 (all P  < 0.05). Table 3 compares baseline characteristics, ovarian response, and embryo quality between pre-EMS and post-EMS I/II groups following PSM1 and PSM2. The dosage and duration of Gn were significantly reduced in the post-EMS I/II group compared to those in the pre-EMS group after both PSM1 and PSM2 ( P   0.05). Post-EMS I/II patients exhibited significantly lower basal LH and E2 levels on trigger day after both PSM analyses ( P  < 0.05). Following PSM1, the post-EMS I/II group had significantly fewer retrieved oocytes, MII oocytes, fertilized oocytes (total/normal), D3 embryos, and high-quality D3 embryos ( P   0.05). Table 4 compares baseline characteristics, ovarian response, and embryo quality between pre-EMS and post-EMS III/IV groups after PSM1 and PSM2. After both PSM1 and PSM2, the post-EMS III/IV group showed significantly higher trigger day luteinizing hormone (LH) levels, but significantly lower basal LH and trigger day estradiol (E2) levels ( P  < 0.05). Compared to the pre-EMS group, the post-EMS III/IV group demonstrated significant reductions in retrieved oocytes, MII oocytes, total fertilized oocytes, normally fertilized oocytes, D3 embryos, and high-quality D3 embryos after both PSM1 and PSM2 (all P  < 0.001). OSI values were also significantly lower in the post-EMS III/IV group after both analyses ( P  < 0.001), while gonadotropin dosage and duration showed no significant differences. After PSM1, the post-EMS III/IV group had significantly fewer abnormally fertilized oocytes and viable blastocysts, as well as a lower high-quality D3 embryo rate (all P  < 0.05). These differences were not observed after PSM2. Before PSM (Table 5 ), clinical pregnancy rates and LBRs were significantly lower in the EMS group compared to the control group, irrespective of prior surgery ( P  < 0.05). This disparity likely reflects confounding by higher female age in the endometriosis cohort ( P   0.05). Table 5 Pregnancy outcomes in the endometriosis and control groups before propensity score matching CON group EMS group Pre-EMS Post-EMS P1 P2 P3 P4 Fresh embryo transfer cases, n 185 212 60 152 Female ages (y) 30.0(28.0-33.0) 32.0(30.0-35.0) 32.5(29.0-35.0) 32.0(30.0-35.0) <0.001 0.013 <0.001 0.768 BMI (kg/m 2 ) 21.05(19.46-23.44) 20.91(19.11-22.66) 20.70(19.01-22.38) 21.03(19.34-22.67) 0.446 0.272 0.698 0.408 D3 embryo transferred, n (%) 167(90.3) 197(91.5) 53(88.3) 141(92.8) 0.668 0.667 0.417 0.297 Endometrial thickness on embryo transfer day, mm 11.5(10.0-13.0) 11.9(10.0-13.0) 12.0(10.6-13.0) 11.5(10.0-13.0) 0.572 0.32 0.966 0.331 HCG positive rates, n (%) 122(65.9) 120(56.6) 34(56.7) 86(56.6) 0.057 0.194 0.078 0.991 Clinical pregnancy rates, n (%) 114(61.6) 99(46.7) 27(45.0) 72(47.4) 0.003 0.024 0.009 0.756 Live birth rates, n (%) 100(54.1) 85(40.1) 21(35.0) 64(42.1) 0.005 0.01 0.029 0.342 Values are expressed as n (%), percentage (%) or median (upper and lower quartile). P1 The significance between the control group and endometriosis group, P2 The significant difference between the control group and non-operated endometrioma group, P3 The significant difference between the control group and operated endometrioma group, P4 The significant difference between Pre-EMS group and Post-EMS group The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, EMS Endometriosis group, including endometrioma with prior surgery or not, BMI Body mass index Table 6 Pregnancy outcomes in the endometriosis and control groups after propensity score matching CON group EMS group P Fresh embryo transfer cases, n 157 157 EMS phenotypes, n (%)  Endometrioma 47(29.9)  Stages I-II 43(27.4)  Stages III-IV 67(42.7) Diameters of the biggest endometrioma, mm  Pre-EMS group 23.7(19.3-28.3)  Post-EMS group 40.5(18.8-50.6) Female ages (y) 31.0(28.0-34.0) 31.0(29.0-34.0) 0.563 BMI (kg/m 2 ) 21.1(19.5-23.4) 20.8(19.1-22.7) 0.165 D3 embryo transferred, n(%) 146(93.0) 141(90.4) 0.403 Endometrial thickness on embryo transfer day, mm 11.5(10.0-13.0) 12.0(10.1-13.0) 0.641 HCG positive rates, n(%) 97(61.8) 94(59.9) 0.729 Clinical pregnancy rates, n(%) 90(57.3) 79(50.3) 0.213 Live birth rates, n(%) 80(51.0) 69(43.9) 0.214 Values are expressed as n (%), percentage (%) or median (upper and lower quartile) Propensity score matching, do analysis after propensity score matching for female age Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group; BMI and the developmental stage of embryos, BMI Body mass index Pregnancy outcomes in the endometriosis and control groups before propensity score matching Values are expressed as n (%), percentage (%) or median (upper and lower quartile). P1 The significance between the control group and endometriosis group, P2 The significant difference between the control group and non-operated endometrioma group, P3 The significant difference between the control group and operated endometrioma group, P4 The significant difference between Pre-EMS group and Post-EMS group The bold number highlights the p which was less than 0.05 Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group, EMS Endometriosis group, including endometrioma with prior surgery or not, BMI Body mass index Pregnancy outcomes in the endometriosis and control groups after propensity score matching Values are expressed as n (%), percentage (%) or median (upper and lower quartile) Propensity score matching, do analysis after propensity score matching for female age Pre-EMS group Endometrioma without surgery group, Post-EMS group Endometrioma with surgery group; BMI and the developmental stage of embryos, BMI Body mass index Supplementary Table S1 presents univariate and multivariate analyses of factors affecting LBRs per fresh embryo transfer. Univariate analysis showed significantly higher LBRs in controls compared to the pre-EMS group (OR 2.185, 95% CI 1.194–3.998; P  = 0.011), but no difference between pre- and post-EMS groups. Female age (OR 0.924), AFC (OR 1.038), and D3 embryo count (OR 1.082) also showed univariate associations with LBRs. After multivariate adjustment, only female age (OR 0.937) and untreated endometrioma diagnosis remained independent predictors of LBRs. AFC and D3 embryo count lost statistical significance in the multivariate model. Figure 2 (A-D) presents the ROC curves evaluating female age, AMH, AFC, and endometrioma size as predictors of one High-quality D3 embryo yield in the EMS group. The optimal thresholds were as follows: female age ≤ 24.5 years[area under the ROC curve (AUC) = 0.594, standard error (SE) = 0.025, 95% CI:0.545–0.643; P  < 0.001; sensitivity = 99.3%, specificity = 2.5%, Youden’s index = 0.018], AMH ≥ 1.17 ng/mL (AUC = 0.703, SE = 0.025, 95% CI:0.654–0.752; P   7.5 (AUC = 0.670, SE = 0.025, 95% CI:0.621–0.720; P  < 0.001; sensitivity = 70.1%, specificity = 57.8%, Youden’s index = 0.279), and endometrioma size ≤ 10.67 mm (AUC = 0.574, SE = 0.026, 95% CI:0.523–0.625; P  < 0.001; sensitivity = 90.2%, specificity = 9.9%, Youden’s index = 0.001). Fig. 2 Receiver operating characteristic (ROC) analyses for predicting a high-quality D3 (Hq-D3) embryo and live birth in the endometriosis (EMS) population. A ROC analysis of anti-Müllerian hormone (AMH) for predicting one Hq-D3 embryo obtained in the EMS group, cut off value=1.17 ng/mL, area under the ROC curve (AUC) = 0.703, standard error (SE) = 0.025, 95% CI:0.654–0.752; P <0.001; sensitivity=71.3%, specificity=66.5%, Youden’s index=0.378. B ROC analysis of antral follicular count (AFC) for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 7.5, AUC=0.670, SE=0.025, 95% CI:0.621–0.720; P <0.001; sensitivity=70.1%, specificity=57.8%, Youden’s index=0.279. C ROC analysis of endometrioma (EMA) size for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 10.67 mm, AUC=0.574, SE=0.026, 95% CI:0.523–0.625;  P <0.001; sensitivity=90.2%, specificity=9.9%, Youden’s index=0.001. D ROC analysis of female age for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 24.5 years, AUC = 0.594, SE=0.025, 95% CI:0.545–0.643; P <0.001; sensitivity=99.3%, specificity=2.5%, Youden’s index=0.018. E ROC analysis of AMH for predicting a live birth in the EMS group, cut off value = 1.18 ng/mL, AUC=0.549, SE=0.044, 95% CI:0.463–0.635; P >0.05; sensitivity=91%, specificity=26.9%, Youden’s index=0.179. F ROC analysis of AFC for predicting a live birth in the EMS group, cut off value = 13.5, AUC=0.535, SE=0.047, 95% CI:0.444–0.626; P >0.05; sensitivity=46.3%, specificity=69.4%, Youden’s index=0.157. G ROC analysis of EMA size for predicting a live birth in the EMS group, cut off value =34.17 mm, AUC=0.508, SE=0.045, 95% CI:0.419–0.597; P >0.05; sensitivity=43.3%, specificity=60.2%, Youden’s index=0.035. H ROC analysis of female age for predicting a live birth in the EMS group, cut off value = 24 years (AUC=0.630, SE=0.044, 95% CI:0.544–0.715; P <0.01; sensitivity=100%, specificity=1.9%, Youden’s index=0.019 Receiver operating characteristic (ROC) analyses for predicting a high-quality D3 (Hq-D3) embryo and live birth in the endometriosis (EMS) population. A ROC analysis of anti-Müllerian hormone (AMH) for predicting one Hq-D3 embryo obtained in the EMS group, cut off value=1.17 ng/mL, area under the ROC curve (AUC) = 0.703, standard error (SE) = 0.025, 95% CI:0.654–0.752; P <0.001; sensitivity=71.3%, specificity=66.5%, Youden’s index=0.378. B ROC analysis of antral follicular count (AFC) for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 7.5, AUC=0.670, SE=0.025, 95% CI:0.621–0.720; P <0.001; sensitivity=70.1%, specificity=57.8%, Youden’s index=0.279. C ROC analysis of endometrioma (EMA) size for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 10.67 mm, AUC=0.574, SE=0.026, 95% CI:0.523–0.625;  P <0.001; sensitivity=90.2%, specificity=9.9%, Youden’s index=0.001. D ROC analysis of female age for predicting one Hq-D3 embryo obtained in the EMS group, cut off value = 24.5 years, AUC = 0.594, SE=0.025, 95% CI:0.545–0.643; P <0.001; sensitivity=99.3%, specificity=2.5%, Youden’s index=0.018. E ROC analysis of AMH for predicting a live birth in the EMS group, cut off value = 1.18 ng/mL, AUC=0.549, SE=0.044, 95% CI:0.463–0.635; P >0.05; sensitivity=91%, specificity=26.9%, Youden’s index=0.179. F ROC analysis of AFC for predicting a live birth in the EMS group, cut off value = 13.5, AUC=0.535, SE=0.047, 95% CI:0.444–0.626; P >0.05; sensitivity=46.3%, specificity=69.4%, Youden’s index=0.157. G ROC analysis of EMA size for predicting a live birth in the EMS group, cut off value =34.17 mm, AUC=0.508, SE=0.045, 95% CI:0.419–0.597; P >0.05; sensitivity=43.3%, specificity=60.2%, Youden’s index=0.035. H ROC analysis of female age for predicting a live birth in the EMS group, cut off value = 24 years (AUC=0.630, SE=0.044, 95% CI:0.544–0.715; P <0.01; sensitivity=100%, specificity=1.9%, Youden’s index=0.019 Figure 2 (E-H) illustrates the ROC analyses for predicting a live birth in the EMS group. Thresholds were: female age ≤ 24 years (AUC = 0.630, SE = 0.044, 95% CI:0.544–0.715; P   0.05; sensitivity = 91%, specificity = 26.9%, Youden’s index = 0.179), AFC > 13.5 (AUC = 0.535, SE = 0.047, 95% CI:0.444–0.626; P  > 0.05; sensitivity = 46.3%, specificity = 69.4%, Youden’s index = 0.157), and endometrioma size ≤ 34.17 mm (AUC = 0.508, SE = 0.045, 95% CI:0.419–0.597; P  > 0.05; sensitivity = 43.3%, specificity = 60.2%, Youden’s index = 0.035). Figure 3 further shows the ROC analyses for predicting one High-quality D3 embryo yield in the pre- and post-EMS groups. In the pre-EMS group (Fig. 3 A to D), thresholds were: AMH > 1.535 ng/mL (AUC = 0.658, SE = 0.052, 95% CI:0.555–0.760; P  = 0.001; sensitivity = 74.9%, specificity = 59.5%, Youden’s index = 0.344), AFC > 8.5(AUC = 0.656, SE = 0.049, 95% CI:0.559–0.752; P  = 0.001; sensitivity = 67.1%, specificity = 61.9%, Youden’s index = 0.290), female age ≤ 21 years (AUC = 0.566, SE = 0.048, 95% CI:0.473–0.660; P  > 0.05; sensitivity = 100%, specificity = 0%, Youden’s index = 0), and endometrioma size ≤ 17.15 mm (AUC = 0.543, SE = 0.051, 95% CI:0.442–0.643; P  > 0.05; sensitivity = 85.8%, specificity = 19.0%, Youden’s index = 0.048). In the post-EMS group (Fig. 3 E to H), thresholds were: AFC > 6.5(AUC = 0.667, SE = 0.03, 95% CI:0.608–0.725; P  < 0.001; sensitivity = 75.0%, specificity = 54.6%, Youden’s index = 0.296), AMH ≥ 1.175 (AUC = 0.703, SE = 0.029, 95% CI:0.647–0.759; P  < 0.001; sensitivity = 64.8%, specificity = 73.1%, Youden’s index = 0.379), female age ≤ 25.5 years (AUC = 0.604, SE = 0.03, 95% CI:0.546–0.662; P  = 0.001; sensitivity = 98.3%, specificity = 5.0%, Youden’s index = 0.033), and endometrioma size ≤ 58.5 mm (AUC = 0.552, SE = 0.03, 95% CI:0.494–0.611; P  > 0.05; sensitivity = 90.2%, specificity = 9.9%, Youden’s index = 0.001). Fig. 3 Receiver operating characteristic (ROC) analyses for predicting a high-quality D3 embryo in the pre-EMS and post-EMS groups. A ROC analysis of anti-Müllerian hormone (AMH) for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 1.535, area under the ROC curve (AUC) =0.658, standard error (SE)=0.052, 95% CI:0.555–0.760; P=0.001 ; sensitivity=74.9%, specificity=59.5%, Youden’s index=0.344. B ROC analysis of antral follicular count (AFC) for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 8.5, AUC=0.656, SE=0.049, 95% CI:0.559-0.752; P=0.001 ; sensitivity=67.1%, specificity=61.9%, Youden’s index=0.290. C ROC analysis of female age for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 21 years, AUC=0.566, SE=0.048, 95% CI:0.473–0.660; P>0.05 ; sensitivity=100%, specificity=0%, Youden’s index=0. D ROC analysis of endometrioma (EMA) size for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 17.15mm, AUC=0.543, SE=0.051, 95% CI:0.442–0.643; P>0.05 ; sensitivity=85.8%, specificity=19.0%, Youden’s index=0.048. E ROC analysis of AMH for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 1.175, AUC=0.703, SE=0.029, 95% CI:0.647-0.759; P<0.001 ; sensitivity=64.8%, specificity=73.1%, Youden’s index=0.379. F ROC analysis of AFC for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 6.5, AUC=0.667, SE=0.03, 95% CI:0.608-0.725; P<0.001 ; sensitivity=75.0%, specificity=54.6%, Youden’s index=0.296. G ROC analysis of female age for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 25.5, AUC=0.604, SE=0.03, 95% CI:0.546-0.662; P=0.001 ; sensitivity=98.3%, specificity=5.0%, Youden’s index=0.033. H ROC analysis of EMA size for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 58.5mm, AUC=0.552, SE=0.03, 95% CI:0.494-0.611; P>0.05 ; sensitivity=90.2%, specificity=9.9%, Youden’s index=0.001 Receiver operating characteristic (ROC) analyses for predicting a high-quality D3 embryo in the pre-EMS and post-EMS groups. A ROC analysis of anti-Müllerian hormone (AMH) for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 1.535, area under the ROC curve (AUC) =0.658, standard error (SE)=0.052, 95% CI:0.555–0.760; P=0.001 ; sensitivity=74.9%, specificity=59.5%, Youden’s index=0.344. B ROC analysis of antral follicular count (AFC) for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 8.5, AUC=0.656, SE=0.049, 95% CI:0.559-0.752; P=0.001 ; sensitivity=67.1%, specificity=61.9%, Youden’s index=0.290. C ROC analysis of female age for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 21 years, AUC=0.566, SE=0.048, 95% CI:0.473–0.660; P>0.05 ; sensitivity=100%, specificity=0%, Youden’s index=0. D ROC analysis of endometrioma (EMA) size for predicting a high-quality D3 embryo obtained in the pre-EMS group, cut off value = 17.15mm, AUC=0.543, SE=0.051, 95% CI:0.442–0.643; P>0.05 ; sensitivity=85.8%, specificity=19.0%, Youden’s index=0.048. E ROC analysis of AMH for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 1.175, AUC=0.703, SE=0.029, 95% CI:0.647-0.759; P<0.001 ; sensitivity=64.8%, specificity=73.1%, Youden’s index=0.379. F ROC analysis of AFC for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 6.5, AUC=0.667, SE=0.03, 95% CI:0.608-0.725; P<0.001 ; sensitivity=75.0%, specificity=54.6%, Youden’s index=0.296. G ROC analysis of female age for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 25.5, AUC=0.604, SE=0.03, 95% CI:0.546-0.662; P=0.001 ; sensitivity=98.3%, specificity=5.0%, Youden’s index=0.033. H ROC analysis of EMA size for predicting a high-quality D3 embryo obtained in the post-EMS group, cut off value = 58.5mm, AUC=0.552, SE=0.03, 95% CI:0.494-0.611; P>0.05 ; sensitivity=90.2%, specificity=9.9%, Youden’s index=0.001

Materials

This retrospective cohort study analyzed 926 consecutive fresh IVF/ICSI cycles at the Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University from June 1, 2017, to September 30, 2022. Participants comprised women with ultrasound/surgically confirmed endometriomas prior to IVF/ICSI. The protocol received ethics approval from our institutional review board (KY2024-R275). Among these, 272 fresh cycles were included in the pre-EMS group, involving women who had one or more in situ ovarian endometriomas and had never undergone ovarian surgery. Additionally, 654 fresh cycles were included in the post-EMS group, involving women who had a history of endometrioma surgery prior to the first IVF/ICSI. Among all analyzed IVF/ICSI cycles in patients with prior EMS surgery, 81.9% occurred within 5 years post-surgery, 14.7% within 6–10 years, and 3.4% beyond 10 years. The surgically identified EMS phenotypes were: ovarian (49.8%), peritoneal (8.2%), combined ovarian and peritoneal (41.0%), combined peritoneal and DIE (0.1%), and combined ovarian, peritoneal, and DIE (0.9%). Patients were staged postoperatively according to the revised American Society for Reproductive Medicine (rASRM) system as follows: Stage I (score 1–5), Stage II (score 6–15), Stage III (score 16–40), and Stage IV (score > 40). The control group (CON group) comprised 530 cycles, involving women with tubal factor or male factor infertility. These women were aged between 21 and 45 years. Of the total cohort, 1159 patients had their first cycle analyzed, whereas 297 patients contributed two or more cycles. AMH levels were measured at least 3 months after surgery and during the year preceding IVF/ICSI treatment. Cases with male infertility factors were excluded if the sperm were obtained from percutaneous epididymal sperm aspiration or testicular sperm extraction. Cases with female factors, such as polycystic ovarian syndrome, recurrent pregnancy loss, untreated gynecological disease, adenomyosis, and genetic disorders, were excluded. These factors are known or suspected to impact early embryo development, ultimately negatively influence the IVF/ICSI outcomes. Figure 1 shows the flow chart for the study. Fig. 1 The flow chart of the study The flow chart of the study Three types of PSM analyses were employed to control for confounding variables. Specifically, PSM1 controlled for female age and BMI; PSM2 controlled for female age, BMI, AMH, AFC, FSH, and E2; and PSM3 controlled for female age, embryo phases, and stimulation protocols. The present study conducted the following comparisons. First, the EMS group was matched with the CON group using PSM1 ( N  = 490; 1:1) and PSM2 ( N  = 390; 1:1). Second, the pre-EMS group was matched with the post-EMS group using PSM1 ( N  = 272; 1:1) and PSM2 ( N  = 224; 1:1). Third, the pre-EMS group was matched with the post-EMS I/II group using PSM1 ( N  = 201) and PSM2 ( N  = 158). Fourth, the pre-EMS group was matched with the post-EMS III/IV group using PSM1 ( N  = 271) and PSM2 ( N  = 198). Fifth, in fresh ET cycles, the EMS group ( N  = 157) was matched with the CON group ( N  = 157) using PSM3. PSM was implemented at a 1:1 ratio with a caliper width of 0.02. Subsequently, case-control analyses were performed to assess folliculogenesis and oocyte competence in aspiration cycles, as well as clinical outcomes following fresh ET. Three pituitary suppression protocols were implemented: (1) Gonadotropin-releasing hormone (GnRH) agonist regimen, single depot injection (0.8–3.75 mg Diphereline, Ipsen Pharma) administered mid-luteal phase of the preceding cycle; (2) GnRH antagonist regimen, daily 0.25 mg cetrorelix (Cetrotide, Merck, Germany) initiated when the dominant follicle reached > 14 mm diameter until human chorionic gonadotropin (hCG) trigger; (3) Progesterone-primed ovarian stimulation, oral medroxyprogesterone acetate (10 mg/day, Meprates, Serum Institute of India) initiated from menstrual cycle day 2 or luteal phase until ovulation trigger. Follicular growth was stimulated using daily administration of human menopausal gonadotropin or recombinant FSH, with the starting dose tailored to the patient’s AMH, BMI, and AFC levels. When follicular criteria were met (≥ 1×>18 mm/≥2×>17 mm/≥3×>16 mm), r-hCG (250 µg, Ovidrel) was administered. Oocytes were retrieved transvaginally 36 h later and fertilized via IVF or ICSI according to seminal quality. Embryo transfers were performed on D3 or D5/6 following oocyte retrieval. Luteal phase support with vaginal and oral progesterone commenced on oocyte retrieval day. Upon positive pregnancy testing, progesterone supplementation continued until 8–10 weeks post-transfer. Embryo quality was assessed using Simon et al.‘s morphological grading system [ 18 ], with high-quality D3 embryos defined as those demonstrating ≤ 20% fragmentation and uniform/mildly irregular blastomere size. Pregnancy was defined as serum β-hCG > 10 mIU/mL (11–13 days post-ET); clinical pregnancy required ultrasound-confirmed intrauterine gestational sac; live birth denoted delivery ≥ 28 gestational weeks. Ovarian sensitivity index (OSI) = (oocytes retrieved/total gonadotropin dose [IU]) × 1000 [ 19 ]. Primary outcome were clinical pregnancy rate and live birth rate (LBR). Secondary outcome included OSI, oocyte yield, number of high-quality D3 embryos, oocyte maturation rate, fertilization rate, and high-quality D3 embryo rate. Statistical analyses utilized SPSS 27.0 (IBM Corp., USA) and GraphPad Prism 10.4 (Software Inc., San Diego, CA). Continuous variables were expressed as mean ± SD (normally distributed; analyzed by independent t-tests) or median with IQR (non-normal; analyzed by Mann-Whitney U/Kruskal-Wallis tests). Categorical data presented as percentages were assessed by χ² tests. Univariate and multivariate logistic regression identified factors associated with IVF/ICSI success. Receiver operating characteristic (ROC) curves determined optimal cutoffs via Youden’s index. Statistical significance threshold was p  < 0.05.

Conclusion

In summary, our study demonstrated that infertile women with EMS, regardless of whether they had undergone prior ovarian surgery, experienced significant reductions in oocyte quantity, ovarian response to stimulation. Additionally, EMS itself at advance stage affected much more. However, EMS did not appear to have a clear adverse effect on pregnancy outcomes, indicating that the disease may not disrupt the chromosomal conditions of the embryos. After ruling out malignant tumors, we recommend the following for EMS patients: (1) Prioritize AMH and AFC testing to identify EMS patients most likely to benefit from IVF, and avoid routine cystectomy in asymptomatic patients with AMH ≤ 1.17 ng/mL or AFC ≤ 7 to preserve ovarian function; (2) Do not use age or endometrioma size as standalone predictors for treatment planning. Future research should prioritize large-scale randomized clinical trials, and investigate applicable biomarkers to predict therapeutic benefit for surgical versus non-surgical approaches.

Discussion

It is currently the dominant opinion that removal of endometriomas before IVF/ICSI decreases oocyte quantity and does not improve IVF outcomes [ 13 , 20 , 21 ]. Previous studies have compared ovarian reserve markers, including oocyte quantity and quality, among control, non-operated endometrioma, and operated endometrioma patients, without ruling out the inherent decrease in oocyte quantity. The present study is the first to eliminate this confounding factor through PSM. It found that endometriosis and endometrioma surgery can decrease oocyte quantity and ovarian response to stimulation drugs, but do not affect the pregnancy outcomes of IVF/ICSI fresh cycles. These findings are consistent with most previous studies [ 13 , 22 – 24 ]. Endometriomas are well established to reduce oocyte yield [ 25 , 26 ] and surgical intervention may further diminish oocyte retrieval and ovarian response to gonadotropins [ 27 ]. Supporting this, a prospective cohort study conducted by Uncu et al. demonstrated that baseline serum AMH levels in the endometrioma group were significantly lower than those in the control group without endometriomas [ 27 ]. As expected, oocyte and embryo numbers were significantly lower in the pre-EMS group compared to the post-EMS and the control groups [ 9 , 13 ]. However, these studies have not excluded some confounders, particularly female age, BMI, AMH, AFC, FSH and E2 levels. Crucially, our PSM2 analysis, adjusting for these confounders, revealed that stage I/II EMS did not significantly impact oocyte/embryo numbers or OSI values (Tables 1 , 2 and 3 ). In contrast, stage III/IV EMS significantly reduced oocyte and embryo yield (Table 4 ), indicating that oocyte quantity is adversely affected specifically by advanced-stage EMS, not early-stage disease. The literature remains contradictory regarding whether poor ovarian response stems primarily from the endometrioma itself or its surgical excision [ 22 , 28 – 31 ]. Our findings suggest that the endometrioma, particularly in advanced stages, directly impairs ovarian responsiveness to gonadotropin(Tables 1 and 4 ). This discrepancy may arise from differing definitions of poor ovarian response and EMS stage. For instance, Demirdag et al. defined poor response as ≤ 5 oocytes retrieved [ 28 ], while Zeng et al. and Wu et al. used a similar definition but did not stratify by EMS stage [ 22 , 31 ]. Therefore, considering ovarian reserve and response, surgical intervention prior to IVF/ICSI cycles may not be routinely recommended. Oocyte and embryo developmental potential can be assessed using markers including fertilization rates, D3 embryo formation, high-quality D3 embryos, blastocyst formation, and pregnancy outcomes. This study found that EMS significantly reduced oocyte maturation, fertilization, and D3 embryo rates, but did not impair blastocyst development (Table 1 ), indicating compromised oocyte quality and early pre-implantation potential (< D3). Although D3 embryo formation rates were significantly reduced in the EMS group compared with controls, blastocyst development rates demonstrated no statistically significant difference between the two groups. This suggests the presence of a compensatory developmental mechanism occurring between days 3 and 5. Whether this “catch-up” affects subsequent implantation or fetal growth requires investigation. Such compensation may involve resource reallocation toward essential mitotic processes at the expense of mitochondrial function. Supporting this, single-cell RNA sequencing of oocytes from endometriosis patients revealed functional enrichment of differentially expressed genes in mitochondrial pathways [ 32 ]. EMS impairs the oocyte microenvironment through iron overload [ 33 ], reactive oxygen/nitrogen species (ROS/RNS) [ 34 , 35 ], and subsequent dysregulation of pro-inflammatory cytokines, adhesion molecules, growth factors, and critical signaling pathways [ 36 – 38 ]. Although reduced pregnancy and LBRs were observed before PSM (Table 5 ), these differences disappeared after matching (Table 6 ), likely attributable to higher maternal age in the EMS cohort. The limited number of fresh embryo transfer cycles here precludes definitive conclusions on pregnancy outcomes. Other factors—such as aberrant decidualization and implantation in eutopic endometrium [ 39 , 40 ]—may also contribute but were beyond this study’s scope and warrant further exploration. The impact of endometrioma surgery on oocyte quality and embryo developmental potential prior to IVF/ICSI remains debated. Our analysis found no significant improvement in fertilization rates, D3 embryo quality, or pregnancy outcomes following surgery (Tables 2 , 3 , 4 , 5 and 6 ), suggesting minimal effects on the oocyte microenvironment [ 41 ]. The pregnancy outcomes of EMS, regardless of endometrioma surgery, were similar to previous studies [ 13 , 22 – 24 ]. Notably, current Chinese guidelines recommend surgical resection for endometriomas ≥ 40 mm in diameter. Surgical indications in this cohort included females who desire fertility goals with large endometrioma size (≥ 4 cm), symptomatic presentation (e.g., chronic pelvic pain), or persistent primary infertility (≥ 1 year of unsuccessful spontaneous conception) without other identifiable causes. Patients with large endometrioma constituted the predominant subgroup in the postoperative endometriosis cohort. Consequently, the post-surgery cohort likely had larger baseline endometriomas than non-operated cases. Meta-analyses indicate that pregnancy outcomes in IVF/ICSI worsen with advancing endometriosis stage [ 42 – 44 ]. Consequently, our finding of comparable pregnancy rates between non-operated and operated patients indirectly suggests potential benefit from endometrioma surgery prior to IVF/ICSI. However, Roustan et al. reported significantly lower clinical pregnancy and LBRs following endometrioma surgery compared to idiopathic causes in patients with diminished ovarian reserve (DOR) [ 45 ]. This discrepancy likely arises because Roustan et al. included only DOR patients, while our cohort encompassed all ovarian reserve levels. The efficacy of surgical intervention in enhancing natural conception remains uncertain [ 46 ]. While some evidence suggests resection of ovarian endometrioma may improve natural conception rates [ 47 ], the benefit appears more pronounced in patients with stage I/II disease [ 46 ]. For stage I/II endometriosis, laparoscopic excision or ablation of lesions combined with adhesiolysis has been shown to increase natural conception rates. However, the role of surgery in improving fertility outcomes for ASRM stage III/IV endometriosis is less clear [ 14 ]. Although our study did not show increased pregnancy rates post-endometrioma surgery, no significant reduction was observed, indicating the procedure is at least not detrimental. Notably, most enrolled patients had undergone about 1 year of unsuccessful conception attempts prior to IVF/ICSI; consequently, this cohort could not validate surgery’s potential benefit for natural conception – a critical knowledge gap requiring future investigation. ROC analyses identified AMH and AFC as predictors of high-quality D3 embryo yield in EMS. Crucially, no parameter reliably predicted live birth (AUC ≤ 0.63), contrasting with Hosseini et al.‘s reported AMH accuracy for pregnancy prediction (AUC = 0.64) [ 48 ]. This discrepancy likely reflected differences in pregnancy outcomes, stimulation protocols, and EMS phenotypes. The failure of ovarian reserve markers to predict live births may stem from unmeasured EMS-specific factors (e.g., inflammation, implantation dysfunction), consistent with findings that inflammatory biomarkers show promise as prognostic markers of oocyte/embryo quality in EMS [ 49 ]. Based on our findings, clinical focus should prioritize optimizing high-quality embryo yield (guided by AMH/AFC thresholds) over direct live birth prediction. Future studies should therefore integrate AMH/AFC with inflammatory biomarkers (e.g., IL-6, TNF-α) or others to improve live birth prediction models. A key strength of this study is the use of PSM for female age, BMI, AFC, AMH, and E2 to minimize confounding. Notably, this is the first study to employ AFC and AMH in PSM analysis to isolate the effects of endometrioma surgery and the presence of endometriomas per se on oocyte quality and pregnancy outcomes, specifically addressing the impact of reduced oocyte quantity. However, limitations exist. First, the retrospective design is susceptible to observational bias. Second, the absence of surgery in the control group means the presence of EMS, particularly peritoneal disease, cannot be entirely excluded. Third, the lack of pathological confirmation for endometrioma diagnosis in non-operated patients, and heterogeneity in surgical management for operated cases, may confound the assessment of independent effects attributable to the disease itself versus surgical intervention.

Introduction

Endometriosis (EMS), an estrogen-dependent disorder, manifests as histologically confirmed endometrial glands and stroma at extrauterine sites, with highest prevalence in pelvic structures including the peritoneum, ovaries, and rectovaginal septum [ 1 ]. Its primary manifestations include superficial peritoneal lesions, deep-infiltrating endometriosis (DIE), and ovarian endometriotic cysts (endometriomas) [ 2 ]. Affecting 5–10% of reproductive-aged women globally, EMS prevalence rises to 35–50% among infertile women [ 1 ], impacting over 176 million women worldwide [ 3 , 4 ]. These women often experience a significant reduction in fecundity, with rates decreasing from 15 to 20% to 2–10% [ 5 ]. In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) offer solutions for conception in EMS-associated infertility. However, clinical studies evaluating IVF/ICSI outcomes in this population—including oocyte yield, maturation rates, fertilization success, embryo quality, clinical pregnancy rates, and live birth rates (LBRs)—have yielded conflicting results. While some studies report compromised outcomes such as reduced oocyte retrieval [ 6 , 7 ], lower fertilization rates [ 7 ], and diminished implantation/pregnancy rates [ 8 ]. others demonstrate comparable outcomes in oocyte yield [ 9 , 10 ], fertilization rates [ 10 , 11 ], clinical pregnancy rates [ 6 , 9 ], and LBRs [ 6 , 9 , 11 ]. Consequently, the precise impact of EMS on IVF/ICSI outcomes remains controversial and warrants further clarification. Another clinical dilemma of whether to perform surgical intervention before IVF/ICSI in endometriosis patients warrants careful consideration. Theoretically, surgical intervention for EMS could create a more favorable environment and improve fertility outcomes before IVF/ICSI cycles [ 12 ]. Multiple investigations have evaluated the clinical implications of ovarian endometriomas and their surgical management on IVF/ICSI outcomes [ 13 – 17 ]. Comparable IVF/ICSI clinical pregnancy outcomes have been reported for women with untreated endometriomas versus those undergoing pre-cycle surgery [ 17 ]. Ovarian reserve depletion following endometrioma excision constitutes a significant iatrogenic threat to fertility outcomes [ 13 – 17 ]. However, comparative analyses inadequately control for female age, BMI, and ovarian reserve biomarkers, such as antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and estradiol, between conservatively managed endometrioma patients, those receiving pre-IVF/ICSI surgical intervention, and non-endometriosis IVF/ICSI controls. To address methodological limitations in existing literature, this study employed propensity score matching (PSM) to mitigate confounding biases. Our objectives were to: (1) Quantitatively assess the impact of EMS on IVF/ICSI outcomes; (2) Determine the clinical utility of preemptive endometrioma resection in infertile EMS patients prior to ART cycles; (3) Establish predictive biomarkers identifying suitable individuals to receive surgery.

Supplementary Material

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Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Fertilization in Vitro Fertilization in Vitro Fertilization in Vitro

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