1. 1 Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Bengt K€allen, M.D., Ph.D.,a Orvar Finnstr€om, M.D., Ph.D.,b Anna Lindam, M.Sc.,c Emma Nilsson, Ph.D.,c Karl-G€osta Nygren, M.D., Ph.D.,d and Petra Otterblad Olausson, Ph.D.c ارائه دهنده :محمد حسین رازی کارشناس ارشد خون شناسی ) پژوهشکده طب تولید مثل)

2. 2 a Tornblad Institute, University of Lund, Lund b Department of Paediatrics, University Hospital, Link € oping c Centre for Epidemiology, National Board of Health and Welfare, Stockholm and d IVF and Fertility Clinic, Sophiahemmet, Stockholm, Sweden

3. 3 Objective:  To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF.

4. 4 Introduction  During the past decade, extension of embryo culture to 5 – 6 days has become part of the routine IVF procedures in some clinics. The embryo then develops into a blastocyst. A number of studies, summarized in a Cochrane review (1), demonstrated a higher pregnancy rate and live birth rate after blastocyst transfer than after cleavagestage transfer

5. 5  A recent study (3) verified the higher pregnancy rate after fresh blastocyst transfer than after cleavage-stage transfer, but for frozen embryos the opposite was seen; therefore, the total pregnancy rate was similar when both fresh and frozen embryo transfers were included.

6. 6  Few studies have investigated the neonatal outcomes after blastocyst transfer. An increased rate of monozygotic twinning and an increased sex ratio have been found  One study described a normal malformation rate for 200 infants (n = 5) born after blastocyst transfer

7. 7  In this study, we have analyzed neonatal outcomes including a number of neonatal diagnoses and the presence of congenital malformations in neonates born after blastocyst transfer, and we compared them with neonates after cleavage-stage embryo transfer.

8. 8 MATERIALS AND METHODS  Data were collected from all IVF clinics in Sweden regarding IVF treatments with an embryo transfer during the period 2002 – 2006.

9. 9  Comparisons were made between infants born after blastocyst transfer and those born after cleavage-stage transfer. Comparisons were also made between infants born after blastocyst transfer or after cleavage-stage transfer and all infants born during 2002 – 2007 and registered in the Medical Birth Register (n = 598,687).

10. 10  Adjustments were made for year of birth, maternal age, parity, smoking habits, and prepregnancy BMI.  This study was performed within the responsibilities of the National Board of Health and Welfare; therefore, no ethical approval from outside ethical committees was needed

11. 11 Results  This study is based on 1,311 infants born to 1,190 women after blastocyst transfer and 12,562 infants born to 11,548 women after cleavage- stage transfer. Births occurred during 2002 – 2007  of multiple births was thus 10% and 8.9%, respectively, and the two rates do not differ significantly

12. 12  There were slightly fewer intracytoplasmic sperm injection procedures associated with blastocyst transfer (43%) than with cleavage- stage transfer (46%), but this difference may be random  there were signs of vanishing twins in 1% after cleavage stage transfer in 1.8 % (x2 =3.2; P=0.07).

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16. 16 DISCUSSION  In our sample, women who had IVF with a blastocyst transfer differed in some aspects from women who had IVF with a cleavage- stage transfer.  Previous studies have shown blastocyst transfer to be more effective than transfer of cleavage stage embryos.

17. 17  The repeated analyses did increase the recorded differences between blastocyst and cleavage-stage transfer groups in regard to preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but not in regard to congenital malformations.

18. 18  The differences between outcomes after blastocyst and cleavagestage transfers could therefore be due to a selection of women undergoing blastocyst transfer, except for the characteristics for which we adjusted.  No major change in the risk estimates for congenital malformations was seen when infants born after blastocyst transfer were compared with infants born after cleavage-stage transfer, after restricting to clinics where blastocyst transfers were made.

19. 19  The differences between neonatal outcome after blastocyst and cleavage-stage transfer are not large, but they may suggest a problem that needs further exploration  It is possible that the extended period in culture increases the risk for monozygotic twinning (1, 4, 5) and for other developmental disturbances, including malformations  Our sample size is too small to study the question of imprinting errors after blastocyst transfer, but no such case was identified.