Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: a retrospective analysis of 67 147 IVF/ICSI cycles

Nicola Marconi* (Corresponding Author), Edwin Amalraj Raja, Siladitya Bhattacharya, Abha Maheshwari

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

STUDY QUESTION: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?

SUMMARY ANSWER: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.

WHAT IS KNOWN ALREADY: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.

STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis.

MAIN RESULTS AND THE ROLE OF CHANCE: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81).

LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.

STUDY FUNDING/COMPETING INTEREST(S): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.

TRIAL REGISTRATION NUMBER: N/A.

Original languageEnglish
Pages (from-to)1716-1725
Number of pages10
JournalHuman Reproduction
Volume34
Issue number9
Early online date16 Aug 2019
DOIs
Publication statusPublished - Sep 2019

Fingerprint

Intracytoplasmic Sperm Injections
Embryo Transfer
Live Birth
Blastocyst
Fertilization in Vitro
Confidence Intervals
Embryonic Structures
Premature Birth
Birth Weight
Embryology
Low Birth Weight Infant
Fertilization
Odds Ratio
Very Low Birth Weight Infant
Sex Ratio
Italy
Gestational Age
Body Mass Index
Cohort Studies
Therapeutics

Keywords

  • blastocyst
  • cleavage stage
  • extended culture
  • perinatal outcome
  • singleton live birth
  • FERTILIZATION
  • PREGNANCIES
  • INCREASED RISK
  • CLEAVAGE TRANSFER
  • MISSING DATA
  • PRETERM BIRTH
  • CULTURE

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer : a retrospective analysis of 67 147 IVF/ICSI cycles. / Marconi, Nicola (Corresponding Author); Raja, Edwin Amalraj; Bhattacharya, Siladitya; Maheshwari, Abha.

In: Human Reproduction, Vol. 34, No. 9, 09.2019, p. 1716-1725.

Research output: Contribution to journalArticle

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abstract = "STUDY QUESTION: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?SUMMARY ANSWER: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.WHAT IS KNOWN ALREADY: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5{\%} confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95{\%} CIs were calculated in the sub-group analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5{\%} CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5{\%} CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5{\%} CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5{\%} CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5{\%} CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5{\%} CI, 0.66-1.65). The risk of congenital anomaly was 16{\%} higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5{\%} CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5{\%} CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5{\%} CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95{\%} CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95{\%} CI, 1.12-1.81).LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.WIDER IMPLICATIONS OF THE FINDINGS: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.STUDY FUNDING/COMPETING INTEREST(S): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.TRIAL REGISTRATION NUMBER: N/A.",
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note = "Acknowledgements The study presented in this article is the result of the research activity for a Thesis presented for the Degree of Master of Science in Obstetrics and Gynaecology at the University of Aberdeen by Dr Nicola Marconi. Funding The research activity of Dr Nicola Marconi was funded by the Italian Scholarship ‘A. Griffini–J. Miglierina’, Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy.",
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T1 - Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer

T2 - a retrospective analysis of 67 147 IVF/ICSI cycles

AU - Marconi, Nicola

AU - Raja, Edwin Amalraj

AU - Bhattacharya, Siladitya

AU - Maheshwari, Abha

N1 - Acknowledgements The study presented in this article is the result of the research activity for a Thesis presented for the Degree of Master of Science in Obstetrics and Gynaecology at the University of Aberdeen by Dr Nicola Marconi. Funding The research activity of Dr Nicola Marconi was funded by the Italian Scholarship ‘A. Griffini–J. Miglierina’, Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy.

PY - 2019/9

Y1 - 2019/9

N2 - STUDY QUESTION: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?SUMMARY ANSWER: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.WHAT IS KNOWN ALREADY: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81).LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.WIDER IMPLICATIONS OF THE FINDINGS: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.STUDY FUNDING/COMPETING INTEREST(S): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.TRIAL REGISTRATION NUMBER: N/A.

AB - STUDY QUESTION: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?SUMMARY ANSWER: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.WHAT IS KNOWN ALREADY: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81).LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.WIDER IMPLICATIONS OF THE FINDINGS: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.STUDY FUNDING/COMPETING INTEREST(S): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.TRIAL REGISTRATION NUMBER: N/A.

KW - blastocyst

KW - cleavage stage

KW - extended culture

KW - perinatal outcome

KW - singleton live birth

KW - FERTILIZATION

KW - PREGNANCIES

KW - INCREASED RISK

KW - CLEAVAGE TRANSFER

KW - MISSING DATA

KW - PRETERM BIRTH

KW - CULTURE

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UR - http://www.mendeley.com/research/perinatal-outcomes-singleton-live-births-after-fresh-blastocyststage-embryo-transfer-retrospective-a

U2 - 10.1093/humrep/dez133

DO - 10.1093/humrep/dez133

M3 - Article

C2 - 31418775

VL - 34

SP - 1716

EP - 1725

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 9

ER -