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. 2024 Aug 16;25(16):8937. doi: 10.3390/ijms25168937

Table 1.

Ovarian stimulation protocol and embryo transfer strategy for adenomyosis.

Ovarian Stimulation Protocol
Study Intervention Results
Rocha et al. (2018) [126]
  • Analysis of 10 adenomyosis studies:

Pooled short protocols (n = 785)
Pooled long protocols (N = 482)
  • A long protocol had better outcomes than a short protocol in CPR (43.3% vs. 31.8%; p = 0.0001), LBR (43% vs. 23.1%; p = 0.005), and MR (18.5% vs. 31.1%; p < 0.0001).

Hou et al. (2020) [127]
  • Observational cohort study:

Controls in long protocol (N = 3471)
Patients in long protocol (N = 127)
Patients in ultra-long protocol (N = 362)
  • Patients with adenomyosis had significantly lower CPRs, IRs, and LBRs in the long protocol than the controls.

  • In patients with adenomyosis, the CPR (OR 1.925, 95% CI 1.137–3.250; p = 0.015), IR (OR 1.694, 95% CI 1.006–2.854; p = 0.047), and LBR (OR 1.704, 95% CI 1.012–2.859; p = 0.044) were significantly increased in the ultra-long protocol than in the long protocol.

Lan et al. (2021) [128]
  • Retrospective study:

Ultra-long GnRHa protocol (N = 212)
Long GnRHa protocol (N = 116)
  • There was a significantly lower MR in the ultra-long GnRHa group than in the long protocol (12.0% vs. 26.5%; p = 0.045).

  • There were no differences in the IR, CPR, or LBR.

Wu et al. (2022) [130]
  • Observational cohort study:

Group A: FET with GnRHa pre-treatment (N = 192)
Group B: fresh ET with ultra-long protocol (N = 241)
Group C: fresh ET with long protocol (N = 104)
  • The IR and LBR were higher in Group A than in Groups B and C, with significantly lower total gonadotrophin dose and stimulation duration.

  • The IR (OR 1.729, 95% CI 1.073–2.788; p = 0.025), CPR (OR 1.665, 95% CI 1.032–2.686; p = 0.037), and LBR (OR 1.694, 95% CI 1.045–2.746; p = 0.033) increased, and the MR (OR 0.203, 95% CI 0.078–0.530; p = 0.001) decreased in Group A compared to Group C.

  • In comparing Groups A and B, FET was a protective factor for the LBR (OR 1.350, 95% CI 1.017–1.792; p = 0.038).

Ge et al. (2023) [129]
  • Retrospective study:

Total of 257 fresh cycles with ultra-long (N = 108), long (N = 56), short (N = 59), and antagonist (N = 34) protocols
Total of 305 FET cycles with embryos from ultra-long (N = 98), long (N = 101), short (N = 52), and antagonist (N = 54) protocols
  • In fresh ET cycles, compared with ultra-long and long protocols, the IR (49.7%, 52.1% vs. 28.2%; p = 0.001) and CPR (64.3%, 57.4% vs. 35.6%; p = 0.004) significantly decreased in the short protocol.

  • In the FET cycles, there were no statistical differences in the IR, CPR, or LBR of embryos derived from different stimulation protocols.

Embryo Transfer Strategy
Study Intervention Results
Niu et al. (2013) [122]
  • Retrospective study:

FET with (N = 194) and without (N = 145) GnRHa pre-treatment
  • There were significantly higher CPRs (51.35% vs. 24.83%), IRs (32.56% vs. 16.07%), and OPRs (48.91% vs. 21.38%) in the GnRHa pre-treatment group.

Park et al. (2016) [121]
  • Retrospective study:

Group A: fresh ET without GnRHa pre-treatment (N = 147)
Group B: fresh ET with GnRHa pre-treatment (N = 105)
Group C: FET with GnRHa pre-treatment (N = 43)
  • The CPR in Group C (39.5%) tended to be higher than those in Group B (30.5%) and Group A (25.2%), but there was no significant difference.

Liang et al. (2019) [131]
  • Retrospective study:

Total of 134 received LNG-IUS (Mirena; Bayer) before FET; 224 controls
  • There was significantly higher OPRs (41.8% vs. 29.5%; p = 0.017), IRs (32.1% vs. 22.1%; p = 0.005), and CPRs (44% versus 33.5%; p = 0.045) in the LNG-IUS group.

Chen et al. (2020) [132]
  • Retrospective study:

Long GnRHa protocol with (N = 48) and without (N = 140) GnRHa pre-treatment
  • In fresh ET, the non-pre-treatment group had a higher LBR (37.7% vs. 21.2%, p = 0.028) and CLBR (40.50% vs. 27.90%, p = 0.019) than the GnRHa pre-treatment group.

Li et al. (2021) [133]
  • Retrospective study:

FET with (N = 160) and without (N = 181) GnRHa pre-treatment (73.8% for 1 month, 15.6% for 2 months, and 10.6% for ≥3 months)
  • No differences were found in the CPRs (40.63% vs. 42.54%; p = 0.72), LBRs (23.75% vs. 23.75%; p = 0.74), miscarriage rates, ectopic pregnancy rates, and preterm birth rates.

Zhang et al. (2022) [134]
  • Retrospective study:

FET with (N = 45) and without (N = 218) GnRHa pre-treatment
  • There were significantly lower MRs (12.5% vs. 37.2%; p = 0.044) and higher LBRs (46.7% vs. 24.8%; p = 0.009) in the GnRHa pre-treatment group.

Feng et al. (2022) [135]
  • Case report:

FET with GnRHa pre-treatment for 2 months and = second FET with dienogest pre-treatment for 3 months
  • The CA-125 level and adenomyoma size were markedly reduced after the GnRHa and dienogest pre-treatments.

  • A singleton pregnancy was achieved at the second FET (with the dienogest pre-treatment).

Yang et al. (2023) [136]
  • Retrospective study:

2048 FET divided into 4 groups: GnRHa-HRT, HRT, OI, and NC
(Subgroups in GnRHa-HRT protocol: one, two, and three or more GnRHa injections)
  • No statistical differences in pregnancy outcomes were found among the four endometrial preparation protocols.

  • In the GnRHa-HRT protocol, the early MR was increased in the subgroup of two compared with one GnRHa injection (18% vs. 6.5%; p = 0.017). No differences were found in the CPR or LBR among the subgroups.

Ge et al. (2023) [129]
  • Retrospective study:

Total of 305 FET cycles with or without GnRHa pre-treatment
  • For women ≥35 years, the IR and CPR were increased in the GnRHa pre-treatment group without statistical differences.

Li et al. (2023) [137]
  • Retrospective study:

Matched 272 cycles in non-downregulation group and 272 in downregulation group
(Subgroups in downregulation group: GnRHa for 1 month, 2 months, or ≥3 months)
  • The pregnancy outcomes in the downregulation group were similar to those in the non-downregulation group, but there was a higher MR (13.4% vs. 3.1%; p = 0.003).

  • The subgroups in fresh ET indicated that the IR (75.0% vs. 39.2%; p = 0.002) and CPR (83.3% vs. 47.0%; p = 0.016) could be improved by prolonged GnRHa downregulation (≥3 months), whereas a late MR was difficult to reverse (30.0% vs. 3.2%; p = 0.017).

CPR: clinical pregnancy rate; LBR: live birth rate; MR: miscarriage rate; IR: implantation rate; OR: odd ratio; CI: confidence interval; ET: embryo transfer; FET: frozen embryo transfer; HRT: hormonal replacement therapy; OI: ovulation induction; NC: natural cycle.