Table 2 Summary of studies describing maternal and neonatal risks based on method of endometrial preparation for autologous frozen embryo transfer

von Versen-Höynck et al. (2019) [28]

United States of America

Prospective cohort study (single center)

2011–2017

Not listed

Modified natural cycle (n = 127) vs. programmed cycle (n = 94)

Programmed cycle vs. modified natural cycle:

• ↑ Preeclampsia 12.8% vs. 3.9% (aOR 3.55; 95% CI 1.20–11.94)

• ↑ Severe preeclampsia 9.6% vs. 0.8% (aOR 15.05; 95% CI 2.59–286.27).

Not studied

Jing et al. (2019) [29]

China

Retrospective Cohort study (single center)

2013–2016

Vitrification

Programmed cycle (n = 2611) vs. natural cycle with luteal progesterone (n = 8, 425)

Programmed cycle vs. natural cycle:

• ↑ Hypertensive disorders of pregnancy 7.2% vs. 4.2% (aOR 1.780; 95% CI 1.262–2.510)

• ↑ Cesarean section 85.9% vs. 78.4% (aOR 1.507; 95% CI 1.195–1.900)

None

Saito et al. (2019) [30]

Japan

Retrospective cohort study (multicenter)

2014

Not listed

Programmed cycle (n = 75,474) and natural cycle (n = 29,760)

Programmed cycle vs. natural cycle:

• ↑ Cesarean section 44.5% vs. 33.7% (aOR 1.69; 95% CI 1.55–1.84)

• ↑ Hypertensive disorders of pregnancy 4% vs. 3% (aOR 1.43; 95% CI 1.14–1.80)

• ↑ Placenta accreta 0.9% vs. 0.1% (aOR 6.91; 95% CI 2.87–16.66)

• ↓ Gestational diabetes mellitus 1.5% vs. 3.3% (aOR 0.52; 95% CI 0.40–0.68)

Programmed cycle vs. natural cycle:

• ↑ Postterm delivery 0.9% vs. 0.3% (aOR 3.28; 95% CI 1.73–6.19)

• ↑ Preterm delivery 8.8% vs. 7.4% (aOR 1.12; 95% CI 1.05–1.40)

Ginström Ernstad et al. (2019) [31]

Sweden

Retrospective cohort study (multicenter)

2005–2015

Vitrification and slow-freezing

Natural cycle (n = 6297) vs. stimulated cycle (n = 1983) vs. programmed cycle (n = 1446)

Programmed cycle vs. natural cycle:

• ↑ Hypertensive disorders of pregnancy 10.5% vs. 6.1% (aOR 1.78; 95% CI 1.43–2.21)

• ↑ Postpartum hemorrhage 19.4% vs. 7.9% (aOR 2.63; 95% CI 2.20–3.13

• ↑ Cesarean delivery 33.3% vs. 26.4% (aOR 1.39; 95% CI 1.21–1.60)

Programmed cycle vs. stimulated cycle:

• ↑ Hypertensive disorders of pregnancy 10.5% vs. 6.6% (aOR 1.61; 95% CI 1.22–2.10)

• ↑ Postpartum hemorrhage 19.4% vs. 8.3% (aOR 2.87; 95% CI 2.29–3.60)

• ↑ Cesarean delivery 33.3% vs. 28.9% (aOR 1.27; 95% CI 1.08–1.50)

Programmed cycle vs. natural cycle had increased risk of:

• ↑ Post-term birth 8.9% vs. 5.8% (aOR 1.59; 95% CI 1.27–2.01)

• ↑ Macrosomia 7.4% vs. 4.6% (aOR 1.62; 95% CI 1.26–2.09)

Programmed cycle vs. stimulated cycle had increased risk of:

• ↑ Post-term birth 8.9% vs. 4.7% (aOR 1.98; 95% CI 1.47–2.68)

• ↑ Macrosomia 7.4% vs. 5.2% (aOR 1.40; 95% CI 1.03–1.90)

Wang et al. (2020) [32]

China

Retrospective cohort study (single center)

2014–2017

Vitrification

Natural cycle (n = 1947) vs. stimulated cycle (n = 1682) vs. programmed cycle (2333)

Not studied

Stimulated cycle vs. natural cycle:

• ↓ Macrosomia 5.1% vs. 6.8% (aOR 0.74; 95% CI 0.57–0.97)

Programmed cycle vs. natural cycle:

• ↑ Large for gestational age 19.9% vs. 16.9% (aOR 1.25; 95% CI 1.05–1.49)

Programmed cycle vs. stimulated cycle:

• ↑ Large for gestational age 19.3% vs. 16.1% (aOR 1.25; 95% CI 1.08–1.46)

• ↑ Macrosomia 7.8% vs. 5.7% (aOR 1.42; 95% CI 1.13–1.80)

Zong et al. (2020) [33]

China

Retrospective cohort study (single center)

2015–2018

Vitrification

Natural cycle (n = 4727) vs programmed cycle (n = 1642) and natural cycle vs. stimulated cycle (n = 517)

Programmed cycle vs. natural cycle:

• ↑ Hypertensive disorders of pregnancy 7.9% vs 3.5% (aOR 2.00; 95% CI 1.54–2.60)

Programmed cycle vs. natural cycle:

• ↑ Low birth weight 4.5% vs. 2.8% (aOR 1.49; 95%CI 1.09–2.06)

• ↑ Preterm birth 7.9% vs. 4.6% (aOR 1.78; 95% CI 1.39–2.28)

Stimulated cycle vs. natural cycle:

• ↑ Preterm birth 7.7% vs. 4.6% (aOR 1.51; 95% CI 1.02–2.23)

Makhijani et al. (2020) [34]

United States of America

Retrospective cohort study (single center)

2013–2018

Vitrification

Natural cycle (n = 384) vs. programmed cycle (n = 391)

Programmed cycle vs. natural cycle:

• ↑overall maternal complications 32.2% vs. 18.8% (aOR 2.21; 95% CI 1.51–3.22)

• ↑hypertensive disorders of pregnancy 15.3% vs. 6.3% (aOR 2.39; 95% CI 1.37–4.17)

None

Zaat et al. (2021) [15]

Netherlands

Follow-up study to the ANTARCTICA randomized controlled trial (multicenter)

2009–2014

Vitrification and slow-freezing

Modified natural cycle (n = 45) and programmed cycle (n = 37)

Modified natural cycle vs. programmed cycle:

• ↓ Hypertensive disorders of pregnancy in 6.7% vs 24.3% (RR 0.2;, 95% CI 0.08–0.94)

None

Hu et al. (2021) [35]

China

Retrospective cohort study (single center)

2013–2019

Vitrification

Natural cycle (n = 3790) vs. programmed cycle (n = 2561) and stimulated cycle (n = 670)

Programmed cycle vs. natural cycle:

• ↑ Cesarean delivery 73% vs. 64% (aOR 1.52; 95% CI 1.35–1.71)

• ↑ Hypertensive disorders of pregnancy 6% vs. 2% (aOR 2.84; 95% CI 2.11–3.83)

Programmed cycle vs. natural cycle:

• ↑ Preterm delivery 12% vs. 8% (aOR 1.49; 95% CI 1.25–1.78)

• ↑ Very Preterm delivery 2% vs. 1% (aOR 2.59; 95% CI 1.56–4.29)

• ↑ Low birthweight 5% vs. 3% (aOR 1.75; 95% CI 1.34–2.28)

• ↑ Macrosomia 13% vs. 10% (aOR 1.19; 95% CI 1.01–1.41)

• ↑ Premature rupture of membranes 2% vs. 1% (aOR 1.67; 95% CI 1.12–2.49)

Stimulated cycle vs. natural cycle:

• ↑ Post-term delivery 0% vs. 0% (aOR 2.72; 95% CI 1.14–6.52)

• ↑ Gestational diabetes mellitus 10% vs. 9% (aOR 1.64, 95% CI 1.28–2.11)