Fresh versus Frozen Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Systematic Review and Meta-Analysis of Neonatal Outcomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.1.1. Inclusion Criteria
2.1.2. Exclusion Criteria
- Use of donor gametes;
- Preimplantation genetic screening or diagnosis;
- Twins, triplets or vanishing twins;
- Ectopic pregnancies;
- Surrogate pregnancies;
- Patients with significant pregestational disease;
- Unknown cause of infertility;
- Low-quality embryo transfers (according to the Istanbul consensus on embryo assessment) [8];
- Incomplete medical data.
2.2. Outcomes
2.2.1. Primary Outcome
2.2.2. Secondary Outcomes
- Small for gestational age (SGA)—birthweight less than the 10th percentile or less than 2 standard deviations for gestational age, according to international child growth standards.
- Large for gestational age (LGA)—birthweight greater than the 90th percentile or more than 2 standard deviations for gestational age, according to international child growth standards.
- Low birthweight (LBW)—weighing less than 2500 grams at birth.
- Macrosomia—weighing more than 4000 grams at birth.
- Congenital malformations—any congenital anomaly found in the newborn
- Neonatal death—death occurring after birth and before day 29.
2.3. Types of Studies
2.4. Search Strategy
- First, we performed a simple search, such as “in vitro fertilization fresh versus frozen neonatal outcome”;
- Next, we added age and study filters, as well as keywords (“preterm birth”, “prematurity”, “SGA”, “LGA”, “macrosomia”, “low birth”, “congenital”, “malformations”, “neonatal death”), which we combined using AND, OR and NOT connectors;
- Furthermore, we used Clinical Queries for Therapy and Prognosis to search for “in vitro fertilization fresh versus frozen embryo neonatal outcome”.
2.5. Study Selection, Data Extraction and Risk of Bias Assessment
2.6. Data Analysis
3. Results
3.1. Search Results
3.2. Included Studies and Their Risk of Bias
3.3. Effect of Fresh Versus Frozen Embryo Transfer (ET vs. FET) on the Incidence of Prematurity
3.4. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Low Birthweight
3.5. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Macrosomia
3.6. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Small-for-Gestational-Age (SGA) Infants
3.7. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Large for Gestational Age (LGA) Infants
3.8. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Congenital Malformations
3.9. Effect of Fresh versus Frozen Embryo Transfer (ET vs. FET) and Neonatal Death
4. Discussion
4.1. Principal Findings
4.2. Comparison with Other Studies
4.3. Explanation of Results
4.4. Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Author, Country, Year of Publication | Type of Study, Duration | Population | Neonatal Outcome | Risk of Bias Assessment |
---|---|---|---|---|
Aflatoonian et al. Iran, 2010 [13] | Prospective cohort 2 years | ET (n = 500) FET (n = 200) | No significant difference between the two groups regarding singleton pregnancies and preterm birth, LBW, neonatal death or congenital malformations. | Maximum score on the NOS |
Aflatoonian et al. Iran, 2016 [14] | Prospective cohort 4 years | ET (n = 1134) FET (n = 285) | No significant difference between the two groups regarding singleton pregnancies and SGA or LBW. FET significantly increases the risk of prematurity in singleton pregnancies, compared to ET (OR 1.65 [1.03–2.66]; p = 0.037). | Maximum score on the NOS |
Belva et al. Belgium, 2016 [15] | Prospective cohort 5 years | ET (n = 1374) FET (n = 827) | FET singletons are less likely to be born SGA (OR 0.55 [0.34–0.9]; p = 0.005). Otherwise, there were comparable neonatal outcomes between the two groups regarding preterm birth, LBW, LGA or congenital malformations. | Maximum score on the NOS |
Cavoretto et al. Italy, 2020 [16] | Prospective cohort 3 years | ET (n = 164) FET (n = 203) | ET significantly increases the incidence of SGA singletons (OR 4.28 [1.37–13.4]; p = 0.008). No significant difference between the two groups regarding singleton pregnancies and LGA or preterm birth. | Maximum score on the NOS |
Cavoretto et al. Italy, 2022 [17] | Prospective cohort 5 years | ET (n = 263) FET (n = 368) | ET significantly increases the incidence of SGA singletons (OR 2.24 [1.38–3.66]; p < 0.001). ET singletons are less likely to be born LGA compared to FET singletons (OR 0.36 [0.18–0.71]; p = 0.002). No significant difference between the two groups regarding singleton pregnancies and preterm birth. | Maximum score on the NOS |
Chen et al. China, 2022 [18] | Retrospective cohort 4 years, 5 months | ET (n = 375) FET (n = 345) | ET is associated with a higher risk of preterm birth (OR 2.21 [1–4.9]; p = 0.046). No significant difference between the two groups regarding singleton pregnancies and macrosomia, LBW or congenital malformations. | NOS score: S ★★★ C ★★ O ★★★ |
Ernstad et al. Sweden, 2019 [19] | Prospective cohort 13 years | ET (n = 4469) FET (n = 3650) | Transfer of vitrified blastocysts was associated with a lower risk of LBW (OR 0.57 [0.44–0.74]) and SGA (OR 0.58 [0.44–0.78]), yet a higher risk of macrosomia (OR 1.77 [1.35–2.31]) and LGA (OR 1.48 [1.18–1.84]). No significant difference between the two groups regarding singleton pregnancies and preterm birth, neonatal death or congenital malformations. | Maximum score on the NOS |
Hsiao et al. Taiwan, 2023 [20] | Retrospective cohort 12 years | ET (n = 428) FET (n = 356) | Singletons conceived via ET were at a higher risk of preterm delivery (OR 1.54 [1–2.38]; p = 0.047) and LBW (OR 1.67 [1.05–2.66]; p = 0.028). No significant difference between the two groups regarding singleton pregnancies and macrosomia, SGA or LGA. | Maximum score on the NOS |
Hwang et al. United States of America, 2019 [21] | Retrospective cohort 9 years, 6 months | ET (n = 12,390) FET (n = 2101) | Infants conceived by FET have higher odds of LGA (OR 1.47 [1.26–1.7]), with lower odds of SGA (OR 0.56 [0.44–0.7]) and LBW (OR 0.72 [0.59–0.88]). There was no significant difference regarding preterm birth or congenital malformations. | Maximum score on the NOS |
Kato et al. Japan, 2012 [22] | Retrospective cohort 3 years | ET (n = 2531) FET (n = 4092) | Infants conceived by FET have lower odds of SGA (OR 0.43 [0.33–0.56]) and LBW (OR 0.65 [0.53–0.79]). There was no significant difference regarding preterm birth, LGA or congenital malformations. | Maximum score on the NOS |
Maheshwari et al. United Kingdom, 2016 [23] | Retrospective cohort 20 years | ET (n = 95,911) FET (n = 16,521) | Singleton pregnancies following FET are associated with a lower risk of LBW and a higher risk of macrosomia. There was no significant difference regarding preterm birth and congenital malformations. * There may be overlapping in selected categories. The authors selected a personalized reporting of data (different confidence interval and p-value, with adjusted risk ratio). | Maximum score on the NOS |
Maheshwari et al. United Kingdom, 2022 [24] | Randomized controlled trial, non-blinded, parallel 3 years, 2 months | ET (n = 309) FET (n = 307) | There was no significant difference regarding singleton pregnancies and preterm delivery, SGA, LGA, LBW, macrosomia, neonatal death or congenital malformations. * The authors selected a personalized reporting of data (different confidence interval, with unadjusted risk ratio). | Moderate risk of bias using the Cochrane Risk of Bias Tool |
Ozgur et al. Turkey, 2015 [25] | Retrospective cohort 2 years | ET (n = 176) FET (n = 116) | There was no significant difference regarding singleton pregnancies and preterm birth or LBW. * Data were reported using the risk ratio. The cohort is slightly different between measurements. | Maximum score on the NOS |
Pelkonen et al. Finland, 2010 [26] | Retrospective cohort 11 years | ET (n = 2942) FET (n = 1830) | The FET group has significantly decreased risks of preterm birth (OR 0.83 [0.71–0.97]), LBW (OR 0.74 [0.62–0.88]) and SGA (OR 0.63 [0.49–0.83]), but an increased risk of LGA (OR 1.7 [1.21–2.40]) in comparison with the ET group. | Maximum score on the NOS |
Pereira et al. United States of America, 2016 [27] | Retrospective cohort 3 years, 9 months | ET (n = 334) FET (n = 427) | There was no significant difference between the two groups regarding singleton pregnancies and preterm delivery or LBW. | Maximum score on the NOS |
Schwarze et al. Chile, 2015 [28] | Retrospective cohort 2 years | ET (n = 6087) FET (n = 2123) | There was no significant difference between the two groups regarding singleton pregnancies and preterm delivery or LBW. | Maximum score on the NOS |
Shavit et al. Canada, 2017 [29] | Retrospective cohort 4 years | ET (n = 575) FET (n = 161) | Singleton pregnancies following FET are associated with higher risk of macrosomia (p = 0.002). There was no significant difference regarding preterm birth, SGA, LBW or congenital malformations. | Maximum score on the NOS |
Stormlund et al. Denmark, 2020 [30] | Randomized controlled trial, non-blinded, parallel 2 years, 4 months | ET (n = 66) FET (n = 61) | Fresh single blastocyst transfer led to an increased risk of preterm birth (p = 0.01), with no other differences observed regarding LBW, SGA or LGA. | Low risk of bias using the Cochrane Risk of Bias Tool |
Zhang et al. China, 2018 [31] | Retrospective cohort 8 years, 2 months | ET (n = 2059) FET (n = 2053) | The FET group has significantly decreased risks of LBW (OR 0.59 [0.37–0.98]; p = 0.026) and SGA (OR 0.73 [0.55–0.99]; p = 0.041), but an increased risk of LGA (OR 1.26 [1.07–1.49]; p = 0.007) and macrosomia (OR 1.43 [1.16–1.75]; p = 0.001) in comparison with the ET group. There was no significant difference regarding congenital malformations. | Maximum score on the NOS |
Zhang et al. China, 2020 [32] | Retrospective cohort 6 years | ET (n = 2125) FET (n = 924) | The incidence of macrosomia in the FET group was higher than in the ET group (OR 1.35 [1.07–1.71]; p = 0.013). Furthermore, FET singletons have a lower risk of LBW comparing to ET singletons (OR 0.67 [0.45–1.00]; p = 0.048). There was no significant difference between the two groups regarding preterm birth. | NOS score: S ★★★ C ★★ O ★★★ |
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Tocariu, R.; Niculae, L.E.; Niculae, A.Ș.; Carp-Velișcu, A.; Brătilă, E. Fresh versus Frozen Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Systematic Review and Meta-Analysis of Neonatal Outcomes. Medicina 2024, 60, 1373. https://doi.org/10.3390/medicina60081373
Tocariu R, Niculae LE, Niculae AȘ, Carp-Velișcu A, Brătilă E. Fresh versus Frozen Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Systematic Review and Meta-Analysis of Neonatal Outcomes. Medicina. 2024; 60(8):1373. https://doi.org/10.3390/medicina60081373
Chicago/Turabian StyleTocariu, Raluca, Lucia Elena Niculae, Alexandru Ștefan Niculae, Andreea Carp-Velișcu, and Elvira Brătilă. 2024. "Fresh versus Frozen Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Systematic Review and Meta-Analysis of Neonatal Outcomes" Medicina 60, no. 8: 1373. https://doi.org/10.3390/medicina60081373