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Cumulative live birth rates following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF: a population-based retrospective cohort study.
Hum Reprod. 2020 Oct 01; 35(10):2365-2374.HR

Abstract

STUDY QUESTION

Is there a difference in the odds of a live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF?

SUMMARY ANSWER

After adjusting for indication bias, there was not enough evidence to suggest a difference in the odds of live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF.

WHAT IS KNOWN ALREADY

Replacement of blastocyst-stage embryos has become the dominant practice in IVF but there is uncertainty about whether this technique offers an improved chance of cumulative live birth over all fresh and frozen-thawed embryo transfer attempts associated with a single oocyte retrieval.

STUDY DESIGN, SIZE, DURATION

National population-based retrospective cohort study of 100 610 couples who began their first IVF/ICSI treatment at a licenced UK clinic between 1 January 1999 and 30 July 2010.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Data from the Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments using autologous gametes between 1999 and 2010 were analysed. The primary outcome was the live birth rate over the first complete cycle of IVF. Cumulative live birth rates (CLBR) were compared for couples who underwent blastocyst and cleavage transfer, and the adjusted odds of live birth over the first complete cycle were estimated for each group using binary logistic regression. This analysis was repeated within groups of female age, oocytes collected and primary versus secondary infertility. Inverse probability of treatment weighting was used to account for the imbalance in couple characteristics between treatment groups.

MAIN RESULTS AND THE ROLE OF CHANCE

In total, 94 294 (93.7%) couples had a cleavage-stage embryo transfer while 6316 (6.3%) received blastocysts. Over the first complete cycle of IVF/ICSI (incorporating all fresh and frozen-thawed embryo transfers associated with the first oocyte retrieval), the CLBR was increased in those who underwent blastocyst transfer (56.5%) compared to cleavage-stage embryo transfer (34.8%). However, after accounting for the imbalance between exposures, blastocyst transfer did not significantly influence the odds of live birth over the first complete cycle (adjusted odds ratio: 1.03 (0.96, 1.10)).

LIMITATIONS, REASONS FOR CAUTION

Limitations of our study include the retrospective nature of the HFEA dataset and availability of linked data up until 2010. We were unable to adjust for some confounders, such as smoking status, BMI and embryo quality, as these data are not collected at national level by the HFEA. Similarly, there may be unknown couple, treatment or clinic variables that may influence our results. We were unable to assess the intended stage of embryo transfer for women who did not have an embryo replaced, and therefore excluded them from our study. Perinatal outcomes were not included in our analyses and would be a useful basis for future study.

WIDER IMPLICATIONS OF THE FINDINGS

Our findings show that blastocyst-stage embryo transfer may offer an improved chance of live birth in both the first fresh and the first complete cycle of IVF/ICSI compared to cleavage-stage transfer, even in couples with typically poorer prognoses. Where possible, offering blastocyst transfer to a wider range of couples may increase cumulative success rates.

STUDY FUNDING/COMPETING INTEREST(S)

N.J.C. received a Wolfson Foundation Intercalated Degree Research Fellowship funded by the Wolfson Foundation, through the Royal College of Physicians. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06) held by D.J.M. The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the Wolfson Foundation. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.

Authors+Show Affiliations

School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.Aberdeen Centre for Women's Health Research, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32949234

Citation

Cameron, N J., et al. "Cumulative Live Birth Rates Following Blastocyst- Versus Cleavage-stage Embryo Transfer in the First Complete Cycle of IVF: a Population-based Retrospective Cohort Study." Human Reproduction (Oxford, England), vol. 35, no. 10, 2020, pp. 2365-2374.
Cameron NJ, Bhattacharya S, McLernon DJ. Cumulative live birth rates following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF: a population-based retrospective cohort study. Hum Reprod. 2020;35(10):2365-2374.
Cameron, N. J., Bhattacharya, S., & McLernon, D. J. (2020). Cumulative live birth rates following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF: a population-based retrospective cohort study. Human Reproduction (Oxford, England), 35(10), 2365-2374. https://doi.org/10.1093/humrep/deaa186
Cameron NJ, Bhattacharya S, McLernon DJ. Cumulative Live Birth Rates Following Blastocyst- Versus Cleavage-stage Embryo Transfer in the First Complete Cycle of IVF: a Population-based Retrospective Cohort Study. Hum Reprod. 2020 Oct 1;35(10):2365-2374. PubMed PMID: 32949234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cumulative live birth rates following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF: a population-based retrospective cohort study. AU - Cameron,N J, AU - Bhattacharya,S, AU - McLernon,D J, PY - 2019/06/10/received PY - 2020/06/19/revised PY - 2020/9/20/pubmed PY - 2020/9/20/medline PY - 2020/9/19/entrez KW - IVF KW - blastocyst KW - cleavage-stage embryo KW - cumulative live birth rate KW - embryo transfer KW - indication bias SP - 2365 EP - 2374 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 35 IS - 10 N2 - STUDY QUESTION: Is there a difference in the odds of a live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF? SUMMARY ANSWER: After adjusting for indication bias, there was not enough evidence to suggest a difference in the odds of live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF. WHAT IS KNOWN ALREADY: Replacement of blastocyst-stage embryos has become the dominant practice in IVF but there is uncertainty about whether this technique offers an improved chance of cumulative live birth over all fresh and frozen-thawed embryo transfer attempts associated with a single oocyte retrieval. STUDY DESIGN, SIZE, DURATION: National population-based retrospective cohort study of 100 610 couples who began their first IVF/ICSI treatment at a licenced UK clinic between 1 January 1999 and 30 July 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from the Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments using autologous gametes between 1999 and 2010 were analysed. The primary outcome was the live birth rate over the first complete cycle of IVF. Cumulative live birth rates (CLBR) were compared for couples who underwent blastocyst and cleavage transfer, and the adjusted odds of live birth over the first complete cycle were estimated for each group using binary logistic regression. This analysis was repeated within groups of female age, oocytes collected and primary versus secondary infertility. Inverse probability of treatment weighting was used to account for the imbalance in couple characteristics between treatment groups. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 94 294 (93.7%) couples had a cleavage-stage embryo transfer while 6316 (6.3%) received blastocysts. Over the first complete cycle of IVF/ICSI (incorporating all fresh and frozen-thawed embryo transfers associated with the first oocyte retrieval), the CLBR was increased in those who underwent blastocyst transfer (56.5%) compared to cleavage-stage embryo transfer (34.8%). However, after accounting for the imbalance between exposures, blastocyst transfer did not significantly influence the odds of live birth over the first complete cycle (adjusted odds ratio: 1.03 (0.96, 1.10)). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study include the retrospective nature of the HFEA dataset and availability of linked data up until 2010. We were unable to adjust for some confounders, such as smoking status, BMI and embryo quality, as these data are not collected at national level by the HFEA. Similarly, there may be unknown couple, treatment or clinic variables that may influence our results. We were unable to assess the intended stage of embryo transfer for women who did not have an embryo replaced, and therefore excluded them from our study. Perinatal outcomes were not included in our analyses and would be a useful basis for future study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that blastocyst-stage embryo transfer may offer an improved chance of live birth in both the first fresh and the first complete cycle of IVF/ICSI compared to cleavage-stage transfer, even in couples with typically poorer prognoses. Where possible, offering blastocyst transfer to a wider range of couples may increase cumulative success rates. STUDY FUNDING/COMPETING INTEREST(S): N.J.C. received a Wolfson Foundation Intercalated Degree Research Fellowship funded by the Wolfson Foundation, through the Royal College of Physicians. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06) held by D.J.M. The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the Wolfson Foundation. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/32949234/Cumulative_live_birth_rates_following_blastocyst__versus_cleavage_stage_embryo_transfer_in_the_first_complete_cycle_of_IVF:_a_population_based_retrospective_cohort_study_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/deaa186 DB - PRIME DP - Unbound Medicine ER -
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