1 Department of Obstetrics and Gynaecology, Queen Mary Hospital, Hong Kong, 2 Prenatal Diagnostic and Counselling Department, Tsan Yuk Hospital, Hong Kong, 3 Hong Kong Prenatal Diagnosis Center, Hong Kong and 4 Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China
5 To whom correspondence should be addressed at: 6/F, Professorial Block, Department of Obstetrics and Gynaecology, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong, China. e-mail: pwhui{at}hkusua.hku.hk
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Abstract |
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Key words: alpha-fetoprotein/frozenthawed embryo transfer/hCG/ICSI/IVF
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Introduction |
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Materials and methods |
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Second-trimester serum assays
The total hCG and AFP serum levels were measured using a micro-particle enzyme immunoassay with the Abbott AXSYM autoanalyser (Abbott Laboratories Ltd, North Point, Hong Kong). Concentrations of the analytes were converted to multiples of the median (MoMs) of the gestational week and adjusted for maternal weight as described previously (Lam et al., 1999). Comparisons were made among pregnancies conceived after fresh embryo transfers, frozen embryo transfer and those conceived spontaneously. A further analysis was performed on the subgroups of pregnancies with conventional insemination (IVF) and ICSI. Not all of the serum marker MoMs fitted a parametric distribution; hence, a Wilcoxon rank-sum test was used to compare values between groups. A P-value < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS version 10.0 computer software.
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Results |
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For median maternal serum AFP MoM, the results were consistently low among the subgroups of fresh embryo transfers. Values were significantly reduced to 0.90 MoM and 0.86 MoM in IVF-embryo transfer (P = 0.04) and ICSI-embryo transfer (P = 0.001) pregnancies respectively. However, the AFP MoM for IVF-frozen embryo transfer pregnancies was 1.20 and was significantly higher (P = 0.01) when compared with that in the controls and with the IVF-embryo transfer and ICSI-frozen embryo transfer subgroups.
The median hCG and AFP MoMs of the ICSI pregnancies were reduced when compared with the conventional IVF pregnancies in both fresh and frozenthawed embryo transfer cycles.
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Discussion |
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Although the present study showed a significantly reduced level of maternal serum AFP in pregnancies after fresh embryo transfers, the data obtained on AFP level were more heterogeneous. The present findings were in agreement with observations made in a Caucasian population (Ribbert et al., 1996; Frishman et al., 1997
), but differed from those found in other series (Barkai et al., 1996
; Heinonen et al., 1996
). To the present authors knowledge, there is no explanation to account for this alteration. The markedly reduced AFP level found in ICSI-embryo transfer pregnancy was also consistent with that of a previous report (Lam et al., 1999
), but opposed the data obtained in the Finnish study (Perheentupa et al., 2002
). The change in direction is towards an increased risk of Downs syndrome, with a higher false-positive rate for second-trimester screening in IVF pregnancies being observed. In addition, a lower level of pregnancy-associated plasma protein-A was also found during the first trimester in these pregnancies (Maymon and Shulman, 2002
). These findings suggested that there was an on-going yet persistent change in the physiology of the IVF pregnancies. Hence, an adjustment of the test results would be needed in order to reduce the unnecessary high false-positive rates for screening in both the first and second trimesters (Frishman et al., 1997
; Lam et al., 1999
; Maymon and Shulman, 2002
).
In the present study, pregnancies conceived after frozen embryo transfer demonstrated elevated trends of hCG and AFP, and these results were similar to those reported in Finland (Perheentupa et al., 2002; Raty et al., 2002
). However, when the maternal serum AFP of IVF-frozen embryo transfer and ICSI-frozen embryo transfer were analysed separately, it was found that the AFP MoM in the subgroup of IVF-frozen embryo transfer pregnancies was 20% higher than that of the controls, while the maternal serum AFP MoM of ICSI-frozen embryo transfer pregnancies was similar to that of the controls. The addition of freezing and thawing procedures in the embryos seems to result in elevation of both hCG and AFP levels as compared with fresh embryos. In contrast to the study in a Finnish population (Perheentupa et al., 2002
), which reported higher hCG and AFP levels after ICSI, a trend towards a reduction in median hCG and AFP MoM was observed in pregnancies conceived after ICSI as compared with those after conventional IVF in the Chinese population. Maternal age is a potential confounding variable that may affect serum AFP concentration (Wald and Watt, 1996
). In the present study population, a weak (but significant) negative correlation between maternal age and AFP MoM was found in the spontaneous pregnancies (Spearmans
= 0.025, P = 0.001), but not in assisted reproduction pregnancies. As the women undergoing frozen embryo transfer were older, maternal age could not account for the raised AFP levels in the frozen embryo transfer pregnancies.
To the best of the present authors knowledge, this is the first report on maternal serum hCG and AFP after ICSI-frozen embryo transfer, as in two previous investigations into frozen embryo transfer pregnancies (Perheentupa et al., 2002; Raty et al., 2002
) the ICSI-frozen embryo transfer pregnancies were not analysed as a discrete subgroup. The median hCG and AFP MoM in ICSI-FET pregnancies were similar to those in controls; hence, the effects of freezing and thawing on hCG and AFP levels appear to be offset by the extra ICSI procedure. Although ICSI is mainly performed for subfertility related to severe male factor, the cause of infertility is unlikely to have a major impact on the serum marker levels. ICSI results in a tiny hole in the zona pellucida of the embryo, and this may have an adverse effect on the freezing and thawing process, as well as on any subsequent development after thawing.
Based on the results of the present study, it is possible that pregnancies conceived after assisted reproduction with a different mode of fertilization and embryo status behave differently from their spontaneous counterparts. Therefore, in future research and clinical management, pregnancies achieved after frozen embryo transfer and ICSI should be regarded as distinct entities from those achieved using fresh embryo transfer and IVF.
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Submitted on September 27, 2002; accepted on December 13, 2002.