The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study

被引:26
作者
Castillo, Catherine M. [1 ]
Harper, Joyce [2 ]
Roberts, Stephen A. [3 ,5 ]
O'Neill, Helen C. [2 ]
Johnstone, Edward D. [1 ,3 ]
Brison, Daniel R. [1 ,3 ,4 ]
机构
[1] Univ Manchester, Maternal & Fetal Hlth Res Ctr, Div Dev Biol & Med, Sch Med Sci,Fac Biol Med & Hlth,Manchester Acad H, Oxford Rd, Manchester M13 9WL, Lancs, England
[2] UCL, Inst Womens Hlth, London WC1E 6HX, England
[3] Manchester Univ Natl Hlth Serv NHS Fdn Trust, Maternal & Fetal Hlth Res Ctr, St Marys Hosp, Manchester Acad Hlth Sci Ctr, Oxford Rd, Manchester M13 9WL, Lancs, England
[4] Manchester Univ NHS Fdn Trust, Dept Reprod Med, Old St Marys Hosp, Manchester Acad Hlth Sci Ctr, Oxford Rd, Manchester M13 9WL, Lancs, England
[5] Univ Manchester, Ctr Biostat, Div Populat Hlth Hlth Serv Res & Primary Care, Sch Hlth Sci,Fac Biol Med & Hlth,Manchester Acad, Oxford Rd, Manchester M13 9PL, Lancs, England
关键词
fertilization in vitro; birth weight; ART; culture media; blastocyst embryo culture; ICSI; live birth rate; pre-term birth; developmental origins of health and disease; assisted reproduction; IN-VITRO FERTILIZATION; LOW-BIRTH-WEIGHT; CLEAVAGE-STAGE; PRETERM BIRTH; BLASTOCYST TRANSFER; CHILDREN BORN; OVARIAN STIMULATION; PERINATAL OUTCOMES; IVF; SINGLE;
D O I
10.1093/hropen/hoz031
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
STUDY QUESTION: Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth? SUMMARY ANSWER: There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses. WHAT IS KNOWN ALREADY: In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health. Although some studies have shown an impact of culture medium type on BW, the interaction between culture medium type and associated culture conditions on both treatment success rates (LBR) and offspring BW is largely unexplored. This study aimed to examine these factors in a large multicentre national survey capturing the range of clinical practice. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, data from a survey circulated to all UK IVF clinics requesting information regarding culture medium type, incubator type, and oxygen level used in ART between January 2011 and December 2013 were merged with routinely recorded treatment and outcome data held in the Human Fertilisation and Embryology Authority Register up to the end of 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty-six (62%) UK clinics responded to the survey. A total of 75287 fresh IVF/ICSI cycles were captured, including 18693 singleton live births. IVF success (live birth, singleton or multiple; LB), singleton gestation and singleton gestation-adjusted BW were analysed using logistic and linear regression models adjusting for patient/treatment characteristics and clinic-specific effects. MAIN RESULTS AND THE ROLE OF CHANCE: Culture medium type was shown to have some impact on LBR (multivariable logistic regression, (MRL); post-regression Wald test, P <0.001), but not on BW (MLR; post-regression Wald test, P =0.215). However, blastocyst culture had the largest observed effect on odds of LBR (odds ratio (OR)=1.35, CI: 1.29-1.42), increased the risk of pre-term birth even when controlling for oxygen tension (MLR; OR=1.42, CI: 1.23-1.63), and gestation-adjusted BW (MLR, beta =38.97 g, CI: 19.42-58.53 g) when compared to cleavage-stage embryo culture. We noted a very strong effect of clinic site on both LBR and BW, thus confounding between treatment practices and clinic site may have masked the effect of culture conditions. LIMITATIONS, REASONS FOR CAUTION: Larger datasets with more inter-centre variation are also needed, with key embryo culture variables comprehensively recorded in national treatment registries. WIDER IMPLICATIONS OF THE FINDINGS: This study is the largest investigation of laboratory environmental effects in IVF on both LBR and singleton BW. Our findings largely agree with the literature, which has failed to show a consistent advantage of one culture media type over another. However, we noted some association of LBR with medium type, and the duration of embryo exposure to laboratory conditions (blastocyst culture) was associated with both LBR and singleton health at birth. Because of the strong effect of clinic site noted, further randomized controlled trials are needed in order to reliably determine the effect of embryo culture on IVF success rates and the growth and health of subsequent offspring.
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页数:13
相关论文
共 55 条
[1]   Time-lapse systems for embryo incubation and assessment in assisted reproduction [J].
Armstrong, Sarah ;
Bhide, Priya ;
Jordan, Vanessa ;
Pacey, Allan ;
Marjoribanks, Jane ;
Farquhar, Cindy .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2019, (05)
[2]   Cleavage stage versus blastocyst stage embryo transfer in assisted conception [J].
Blake, D. A. ;
Farquhar, C. M. ;
Johnson, N. ;
Proctor, M. .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2007, (04)
[3]   ACE consensus meeting report: Culture systems [J].
Bolton, Virginia N. ;
Cutting, Rachel ;
Clarke, Helen ;
Brison, Daniel R. .
HUMAN FERTILITY, 2014, 17 (04) :239-251
[4]   Ovarian stimulation for in vitro fertilization alters the intrauterine cytokine, chemokine, and growth factor milieu encountered by the embryo [J].
Boomsma, Carolien M. ;
Kavelaars, Annemieke ;
Eijkemans, Marinus J. C. ;
Fauser, Bart C. J. M. ;
Heijnen, Cobi J. ;
Macklon, Nick S. .
FERTILITY AND STERILITY, 2010, 94 (05) :1764-1768
[5]   Maternal age ≥ 45 years and maternal and perinatal outcomes: A review of the evidence [J].
Carolan, Mary .
MIDWIFERY, 2013, 29 (05) :479-489
[6]   Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand [J].
Chambers, Georgina M. ;
Chughtai, Abrar A. ;
Farquhar, Cynthia M. ;
Wang, Yueping A. .
FERTILITY AND STERILITY, 2015, 104 (04) :997-1003
[7]   The placenta: phenotypic and epigenetic modifications induced by Assisted Reproductive Technologies throughout pregnancy [J].
Choux, Cecile ;
Carmignac, Virginie ;
Bruno, Celine ;
Sagot, Paul ;
Vaiman, Daniel ;
Fauque, Patricia .
CLINICAL EPIGENETICS, 2015, 7
[8]   IVF culture media: past, present and future [J].
Chronopoulou, Elpiniki ;
Harper, Joyce C. .
HUMAN REPRODUCTION UPDATE, 2015, 21 (01) :39-55
[9]   Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: a systematic review and meta-analysis [J].
Dar, S. ;
Lazer, T. ;
Shah, P. S. ;
Librach, C. L. .
HUMAN REPRODUCTION UPDATE, 2014, 20 (03) :439-448
[10]  
Dieamant F, 2017, J BRAS REPROD ASSIST, V21, P240, DOI 10.5935/1518-0557.20170045