Introduction
Methods
Data sources
Study selection
Risk of bias assessment
Morphokinetic evaluation
Results
Author | Type of Study | Inclusion Criteria | Study subjects | Number of Subjects |
---|---|---|---|---|
Boynukalin et al., 2019 [16] | Retrospective observational study | 1. Age < 40 2. No male factor infertility 3. No structural or numerical chromosomal errors necessitating preimplantation genetic diagnosis 4. No uterine anomalies or PCOS | 53 study patients (diagnosed surgically and sonographically) 30 control patients (tubal infertility) | 439 embryos: 1. Study group: 53 patients (264 embryos) 2. Control group: 29 patients (175 embryos) |
Demirel et al., 2016 [17] | Observational prospective study | 1. Age < 42 2. No previous IVF/ICSI treatment 3. Day 3 FSH < 10 mIU/mL 4. AFC 5 5. At least 2 oocytes from each ovary 6. Planned ICSI and fresh blastocyst transfer on day 5 | 20 study subjects (diagnosed sonographically): Study group: ovary with endometrioma ≤ 4 cm Control group: normal contralateral ovary | 128 embryos from 20 infertility women: 1. Study group: 69 embryos 2. Control group: 59 embryos |
Freis, et al., 2018 [18] | Retrospective study | 1. Age 18—45 2. No confounding comorbidities (PCOS, pathological spermiograms, structural or numerical genetic abnormalities, preimplantation genetic screening) | 72 study patients (diagnosed surgically) 96 control patients (tubal factor, unexplained infertility, or prolonged infertility) | 477 embryos: 1. Study group: 72 patients (213 embryos) 2. Control group: 96 patients (264 embryos) |
Llarena, et all, 2022 [19] | Retrospective study | 1. Ages 18—39 2. No PCOS, recurrent pregnancy loss, unexplained infertility and diminished ovarian reserve | 126 study patients (diagnosed surgically or sonographically) 233 control patients (tubal factor, unexplained infertility or prolonged infertility) | 3471 embryos: 1. Study group: 126 patients (1078 embryos) 2. Control group: 233 patients (2393 embryos) |
Schenk et al., 2019 [20] | Retrospective study | 1. BMI 17.5–30 2. Age 26–39 3. No nicotine abuse 4. No endocrine disorders (PCOS, POI, menopause, hypothalamic amenorrhea, CAH) 5. No diabetes mellitus 6. No chronic inflammation 7. No known genetic disorders 8. No severe OATS | 86 study patients 77 control patients (unexplained or prolonged infertility) | 1148 embryos: 1. Study group: 86 patients (552 embryos) 2. Control group: 77 patients (596 embryos) |
Stimulation protocol, oocyte yield and fertilization
Study (n = 889 subjects) | Stimulation Protocol | Oocyte yield Endo vs controls | Mature oocytes (MII) Endo vs. controls | Fertilization Endo vs controls |
---|---|---|---|---|
Boynukalin et al., 2019 [16] | GnRH antagonist protocol | 7.50 ± 3.58 vs 8.44 ± 1.21 (p < 0.05) | 5.84 ± 3.24 vs 7.2 ± 0.9 (p < 0.01) | 84.5 vs 82.3 (not significant |
Demirel et al., 2016 [17] | GnRH antagonist protocol | 5.3 ± 3.6 vs 4.3 ± 2.7 (p 0.3) | 4.2 ± 2.6 vs 3.6 ± 2.4 (p 0.5) | 82 (69/84) vs 85 (59/69) (p 0.7) |
Freis, et al., 2018 [18] | Ultralong and long agonist | 9.6 ± 5.0 vs 10.0 ± 5.1 (p not significant) | – | 60.4 ± 23.8 vs 57 ± 23.8 (p not significant) |
Llarena, et all, 2022 [19] | Antagonist, microdose flare, standard long, agonist –antagonist, and mini-stimulation protocols | 12.6 ± 8 vs 15.2 ± 8.2 (p 0.001) | 8.4 ± 4.8 vs 10.5 ± 5.9 (p < 0.001) | 0.80 [0.67, 0.94] vs 0.78 [0.63, 0.89] (p 0.036) |
Schenk et al., 2019 [20] | GnRH antagonist protocol | 8.9 [7.8, 10.1] vs 7.9 [7.1, 8.8] | – | – |
Embryo morphokinetic changes
First embryo cell cycle (VP and ECC1)
Study | tPB2 Endo vs Controls | tPNa Endo vs Controls | tPNf Endo vs Controls | ECC1 Endo vs Controls | VP Endo vs Controls |
---|---|---|---|---|---|
Boynukalin et al., 2019 [16] | 6.51 ± 9.07 vs 3.71 ± 1.98 (p < 0.01) | 12.50 ± 7.87 vs 11.13 ± 3.74 (p < 0.01) | 25.90 ± 6.31 vs 25.30 ± 7.87 (not significant) | 22.19 ± 8.23 vs 24.56 ± 5.66 (p < 0.01) | 13.25 ± 6.23 vs 14.87 ± 7.79 (not significant) |
Demirel et al., 2016 [17] | – | – | – | – | – |
Freis, et al., 2018 [18] | – | – | – | – | – |
Llarena, et all, 2022 [19] | – | – | – | – | – |
Schenk et al., 2019 [20] | – | – | 25.7 [25.4, 26.0] vs 24.9 [24.6, 25.2] | – | – |
Second embryo cell cycle (ECC2)
Study | t2 Endo vs Controls | t3 Endo vs Controls | t4 Endo vs Controls | ECC2 Endo vs Controls | S2 Endo vs Controls | CS2-4 Endo vs Controls | DR Endo vs Controls |
---|---|---|---|---|---|---|---|
Boynukalin et al., 2019 [16] | 28.64 ± 5.24 vs 28.25 ± 5.40 (not significant) | 38.02 ± 6.87 vs 37.67 ± 6.33 (not significant) | 41.44 ± 7.35 vs 40.19 ± 6.29 (not significant) | 12.87 ± 5.47 vs 12.02 ± 4.73 (not significant) | 3.40 ± 5.31 vs 2.53 ± 4.24 (p < 0.01) | – | – |
Demirel et al., 2016 [17] | 29.3 vs 28.6 h (p 0.2) | – | – | 8.9 vs 9.9 h (p 0.5) | 3.9 vs 2.6 h (p 0.6) | – | – |
Freis, et al., 2018 [18] | 2.7 (0.7–5.3) vs 2.6 (1.9–8.7) (not significant) | 14.2 (6.7–21.6) vs 14.3 (12.1–24.5) (not significant) | 15.4 (7.2–37.0) vs 15.0 (12.4–43.7) (not significant) | 12.4 (0.0–33.5) vs 12.7 (0 .0–29.4) (not significant) | 0.7 (0.0–20.8) vs 0.6 (0.0–10.5) (not significant) | 0.1 (0.0–0.8) vs 0.1 (0.0–1.0) (not significant) | 0.8 (0.0–8.0) vs 0.8 (0.0–13.1) (not significant) |
Llarena, et all, 2022 [19] | 28.1 ± 5.6 vs 27.2 ± 4.7 (p < 0.001) | 38.2 ± 7.1 vs 36.8 ± 5.9 (p < 0.001) | 41.0 ± 8.2 vs 39.5 ± 7.2 (p < 0.001) | 11.3 [9.7, 12.5] vs 11.2 [9.5, 12.2] (p 0.003) | 0.67 [0.33, 2.3] vs 0.67 [0.33, 2.2] (p 0.64) | – | – |
Schenk et al., 2019 [20] | 29.4 [29.0, 29.9] vs 28.5 [28.1, 29.0] | 39.1 [38.5, 39.6] vs 37.9 [37.3, 38.5] | 41.8 [41.3, 42.4] vs 41.5 [40.9, 42.2] | 25.7 [25.4, 26.0] vs 24.9 [24.6, 25.2] | Significantly lower in the Endo (p < 0.05) | – | – |
Third embryo cell cycle (ECC3)
Study | t5 Endo vs Controls | t6 Endo vs Controls | t7 Endo vs Controls | t8 Endo vs Controls | t9 Endo vs Controls | ECC3 Endo vs Controls | s3 Endo vs Controls | CS2-8 Endo vs Controls | CS4-8 Endo vs Controls |
---|---|---|---|---|---|---|---|---|---|
Boynukalin et al., 2019 [16] | 50.51 ± 9.86 vs 49.76 ± 10.41 (not significant) | 55.28 ± 10.14 vs 53.77 ± 9.91 (not significant) | 58.11 ± 10.14 vs 58.33 ± 10.28 (not significant) | 62.67 ± 11.80 vs 61.45 ± 11.09 (not significant) | 71.57 ± 13.37 vs 69.62 ± 11.58 (not significant) | 22.56 ± 9.46 vs 22.03 ± 9.30 (not significant) | 12.40 ± 9.20 vs 12.59 ± 10.01 (not significant) | – | – |
Demirel et al., 2016 [17] | 52.3 vs 52.5 h (p 0.9) | – | – | – | – | – | – | – | – |
Freis, et al., 2018 [18] | 28.0 (5.8–55.7) vs 27.9 (19.2–53.0) (not significant) | 30.0 (6.8–51.6) vs 29.4 (23.6–64.0) (not significant) | 32.8 (8.5–56.0) vs 30.9 (25.2–66.7) (not significant) | 34.3 (11.5–68.7) vs 33.0 (25.3–59.9) (not significant) | 50.0 (16.8–73.2) vs 50.3 (28.4–74.7) (not significant) | 18.0 (3.4–53.6) vs 17.8 (5.5–47.3) (not significant) | 5.6 (1.4–36.0) vs 4.5 (0.9–27.5) (not significant) | 0.7 (0.0—0.93) vs 0.8 (0.0–0.94) (p < .05) | 0.4 (0.1–1.0) vs 0.3 (0.1–1.0) (p < .05) |
Llarena, et all, 2022 [19] | 51.1 ± 10.5 vs 49.4 ± 9.4 (p < 0.001) | – | 59.2 ± 10.9 vs 57.5 ± 10.2 (p < 0.001) | 61.9 ± 12.0 vs 60.0 ± 11.2 (p < 0.001) | 72.2 ± 12.3 vs 70.1 ± 11.8 (p < 0.001) | 13.2 [11.0, 15.7] vs 13.0 [10.9, 15.1] (p 0.046) | – | – | – |
Schenk et al., 2019 [20] | 52.5 [51.6, 53.3] vs 51.3 [50.4, 52.3] | 56.1 [55.3, 57.0] vs 55.4 [54.6, 56.3] | 60.0 [59.1, 61.0] vs 59.8 [58.8, 60.7] | 63.7 [62.6, 64.9] vs 62.6 [61.5, 63.7] | 74.2 [72.7, 75.8] vs 72.8 [71.3, 74.4] | No difference in ECC3 | No difference in s3 | – | – |
Morula formation and blastulation
Study | tM Endo vs Controls | tSB Endo vs Controls | tB Endo vs Controls | tEB Endo vs Controls | DC Endo vs Controls | DR Endo vs Controls |
---|---|---|---|---|---|---|
Boynukalin et al., 2019 [16] | – | – | – | – | – | – |
Demirel et al., 2016 [17] | – | – | – | – | – | – |
Freis, et al., 2018 [18] | – | – | – | – | 9/72 (12.5%) vs 4/96 (4.2%) (p 0.076) | 0.8 (0.0–8.0) vs 0.8 (0.0–13.1) (not significant) |
Llarena, et all, 2022 [19] | 93.1 ± 11.5 vs 92.1 ± 11.2 (p 0.036) | 103.2 ± 10.3 vs 101.4 ± 10.0 (p < 0.001) | 108.4 ± 10.2 vs 106.4 ± 10.0 (p < 0.001) | 116.5 ± 10.3 vs 114.5 ± 10.1 (p < 0.001) | 8.6% vs 9.2% (p 0.56) | – |
Schenk et al., 2019 [20] | 87.4 [86.1, 88.7] vs 86.1 [84.6, 87.6] | – | – | – | 17 cases (3.1%) vs 17 cases (2.9%) (not significant) | – |
Embryo quality and blastocyst development
Study | Blastocyst Development/Quality Endo vs Controls | Implantation Rate Endo vs Controls | Pregnancy Rate Endo vs Controls |
---|---|---|---|
Boynukalin et al., 2019 [16] | 30% vs 54% Day 3 embryos (p < 0.01) | – | 41.5% vs 44.8% |
Demirel et al., 2016 [17] | 15% vs 19% (p 0.3) | – | 50% vs 57% (p < 0.05) |
Freis, et al., 2018 [18] | – | – | – |
Llarena, et all, 2022 [19] | 59.95% vs 66.2% (p < 0.001) | 111/201 (55%) vs 212/385 (55%) | 63.6% vs 66.5% (p 0.56) |
Schenk et al., 2019 [20] | – | 29.6% (Min: 33.3%; Mild: 21.2%; Mod: 22.5%, Severe: 14.3%) vs 31.8% | 25.2% vs 25.2% |
Implantation and pregnancy
Morphokinetic parameter | Non implanting embryo | Implanting embryo | p value | |
---|---|---|---|---|
Endometriosis group | t7 | 58.6 ± 8.2 | 55.2 ± 7.1 | 0.003 |
tSB | 102.1 ± 9.2 | 97.5 ± 7.1 | < 0.001 | |
tB | 106.3 ± 8.6 | 102.5 ± 7.0 | < 0.001 | |
tM | 91.7 ± 10.7 | 87.8 ± 9.0 | ns | |
tEB | 113.9 ± 8.2 | 110.6 ± 8.1 | ns | |
tSC | 86.0 ± 11.7 | 81.6 ± 8.8 | ns | |
Control group | tM | 91.8 ± 10.7 | 87.7 ± 8.2 | < 0.001 |
tSB | 100.8 ± 7.9 | 97.2 ± 7.3 | < 0.001 | |
tB | 105.7 ± 8.1 | 102.3 ± 7.5 | < 0.001 | |
tEB | 113.6 ± 8.4 | 109.8 ± 7.1 | < 0.001 | |
tSC | 84.7 ± 9.7 | 81.3 ± 9.0 | < 0.001 |