http://humrep.oxfordjournals.org/content/24/9/2158.long
Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data
- U.-B. Wennerholm1,9,
- V. Söderström-Anttila2,
- C. Bergh3,
- K. Aittomäki4,
- J. Hazekamp5,
- K.-G. Nygren6,
- A. Selbing7 and
- A. Loft8
+Author Affiliations
- 9Correspondence address. Tel: +46-31-3435580; Fax: +46-31-258374; E-mail:ulla-britt.wennerholm@vgregion.se
- Received February 6, 2009.
- Revision received April 1, 2009.
- Accepted April 7, 2009.
Abstract
BACKGROUND An estimated 3.5 million children have been born to date using assisted reproduction technologies. We reviewed the data in order to evaluate current knowledge of medical outcome for IVF/ICSI children born after cryopreservation, slow freezing and vitrification of early cleavage stage embryos, blastocysts and oocytes.
METHODS A systematic review was performed. We searched the PubMed, Cochrane and Embase databases from 1984 to September 2008. Inclusion criteria for slow freezing of early cleavage stage embryos were controlled studies reporting perinatal or child outcomes. For slow freezing and vitrification of blastocysts and oocytes, and vitrification of early cleavage stage embryos, case reports on perinatal or child outcomes were also included. Three reviewers independently read and evaluated all selected studies.
RESULTS For early cleavage embryos, data from controlled studies indicated a better or at least as good obstetric outcome, measured as preterm birth and low birthweight for children born after cryopreservation, as compared with children born after fresh cycles. Most studies found comparable malformation rates between frozen and fresh IVF/ICSI. For slow freezing of blastocysts and for vitrification of early cleavage stage embryos, blastocysts and oocytes, limited neonatal data was reported. We found no long-term child follow-up data for any cryopreservation technique.
CONCLUSION Data concerning infant outcome after slow freezing of embryos was reassuring. Properly controlled follow-up studies of neonatal outcome are needed after slow freezing of blastocysts and after vitrification of early cleavage stage embryos, blastocysts and oocytes. In addition, child long-term follow-up studies for all cryopreservation techniques are essential.
Table II
Preterm birth and low birthweight of singletons and twins after transfer of frozen and fresh IVF and ICSI early cleavage stage embryos
| Reference, country | Cryo infants (IVF/ICSI) | Fresh infants (IVF/ICSI and/or NC) | Cryo singletons PTB N (%) | Fresh singletons PTB N (%) | OR/AOR (95% CI) and/orP-value | Cryo singletons LBW N (%) | Fresh singletons LBW N (%) | OR/AOR (95% CI) and/orP-value | Cryo twins PTB N (%) | Fresh twins PTB N (%) | OR/AOR (95% CI) and/orP-value | Cryo twins LBW N (%) | Fresh twins LBW N (%) | OR/AOR (95% CI) and/orP-value |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wada et al. (1994) UK | IVF: 177 singletons, 78 twins | IVF: 527 singletons, 262 twins | 19/158 (12%) | 67/494 (14%) | P > 0.05 | 13/177 (7%) | 68/527 (13%) | P > 0.05 | 12/36 (33%) | 72/125 (58%) | P < 0.05 | 30/78 (38%) | 140/262 (53%) | P < 0.05 |
| Sutcliffe et al. (1995a), UK | 68 singletons, 20 twins, 3 triplets | 81 NC singletons, 2 NC twins | 7/68 (10.3) | 6/82a(7.4) | NA | NA | NA | NA | NA | NA | NA | |||
| Schieve et al. (2002) USA | 42 463 infantsb (8.9% cryo, 78.0% fresh) | NA | NA | NA (10.5) | NA (13.6) | NA | NA | NA | NA (49.5) | NA (56.0) | NA | |||
| Wang et al. (2005), Australia | 5120b | 12 604b | 437 (11.4) | 1008 (13.1) | 1.3 (1.1–1.6)c | 277 (7.2) | 829 (10.8) | 1.6 (1.3–2.0)c | NA (59.5) | NA (61.3) | NA | 565 (47.3) | 2385 (55.2) | 1.3 (1.1–1.6)c |
| Kallen et al. (2005a, b, c), Sweden | IVF: 1055b | IVF: 10 228b | NA | NA | 0.69 (0.50–0.95)d | NA | NA | 0.49 (0.02–0.75)d | NA | NA | NA | NA | ||
| ICSI: 419b | ICSI: 4545b | NA | NA | 0.97 (0.55–1.38)d | NA | NA | 0.99 (0.59–1.66)d | NA | NA | NA | NA | |||
| Shih et al. (2008), Australia | 2387 cryo IVF/ICSI singleton first births; 429 sets of IVF/ICSI twins | 3110 fresh IVF/ICSI singleton first births; 825 sets of IVF/ICSI twins | NA (9.2) | NA (12.3) | 1.4 (1.1–1.6)e; <0.001 | NA (6.5) | NA (11.6) | 1.9 (1.6–2.4)e; <0.001 | 206/431 (48) | 428/828 (52) | NS | 184/431 (43)f | 418/835 (50)f | 0.013 |
| Belva et al. (2008), Belgium | 384 IVF (281 singletons, 98 twins) | 2920 IVF (1523 singletons, 1251 twins) | 34/281 (11.9) | 140/1523 (9.0) | 1.38 (0.92–2.05)g | 20/281 (7.1) | 121/1523 (7.9) | 0.64 (0.54–1.45)g | 62/98 (62.0) | 600/1251 (47.6) | 1.77 (1.17–2.69)g | 49/98 (50.0) | 568/1251 (45.1) | 1.21 (0.80–1.81)g |
| 539 ICSI (381 singletons, 155 twins) | 2799 ICSI (1476 singletons, 1211 twins) | 44/381 (11.4) | 126/1476 (8.4) | 1.41 (0.98–2.03)h | 24/381 (6.2) | 106/1476 (7.2) | 0.87 (0.55–1.37)h | 92/155 (57.5) | 669/1211 (54.6) | 1.13 (0.81–1.58)h | 70/155 (45.1) | 593/1211 (48.1) | 0.86 (0.61–1.20)h | |
- AOR: adjusted odds ratio; LBW: low birthweight; NA: not available; NC: naturally conceived; OR: odds ratio; PTB: preterm birth.
- aInclude one set of twins.
- bSingletons and multiples.
- cCryo embryos = 1.0, AOR (99% CI), adjusted for maternal age, parity, cause of infertility (male or female), number of embryos transferred, type of embryos and type of procedure.
- dFresh IVF embryos = 1.0, adjusted for year of birth, maternal age, parity, smoking and years of involuntary childlessness.
- eCryo embryos = 1.0 (95% CI), adjusted for gestation, sex, parity, birth defect, perinatal death, semi-private socio-economic status, Cesarean section, era <1993.
- fCombined low birthweight (<5000 g). Numbers of births differs from those mentioned in methods section.
- gFresh IVF embryos = 1.0.
- hFresh ICSI embryos = 1.0.
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