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Justification
Introduction
Transfer of blastocysts is a promising new technique from which some patients may benefit,
especially those patients with large numbers of embryos on day two or three, where almost
any selection for transfer seems arbitrary. We have previously presented data to show that
the embryo morphology on day three is of limited value for blastocyst formation12. A full
article is now in print3 However it is doubtful whether all patients will benefit: Two
prospective
randomized trials have not shown any benefit from postponing the transfer to
day 5 when all patients can enter, regardless of the number of embryos to start with.4,5
Especially in the latter study, the number of patients that did not proceed to transfer
was high, and the miscarriage rate was 50%. It thus seems that the benefit for some as a
result of the better embryo selection does not outweigh the risk of the longer
extra corporeal existence of the embryos. Nevertheless those patients that have many
embryos to choose from, whether or not of good morphological appearance on day 2 or 3, may
benefit from this procedure.
Why an international registration ?
There have been numerous reports on the safety of transfer of blastocysts for the
offspring in mice, sheep and cattle. In ruminants a large business has arisen to produce
cows with certain desired qualities, and the production of embryos has proceeded beyond
just the formation of embryos from oocytes that had their resumption of meiosis in vivo,
after the hCG injection. In these latter group it now has been published however that
there is an increased risk of the large calf syndrome of about threefold 6 In addition it
has been published that the risk of congenital abnormalities has risen more then fourfold
from 0,7 % to 3.2 %7. Table 1 depicts the incidence of congenital abnormalities in
ruminants in two groups: after artificial insemination (AI) in almost 2800 cows in
comparison to in vitro production (IVP) in over 900 cows.
| |
AI |
% |
IVP |
% |
| Total no of cows |
2787 |
|
944 |
|
| Hydroallantois |
2 |
0.07 % |
17 |
1.8 % |
| Abnormal Limbs |
2 |
0.07 % |
8 |
0.8 % |
| Stretched Limb |
1 |
0.04 % |
0 |
|
| Bulldog Calf |
1 |
0.04 % |
1 |
0.1 % |
| Freemartin |
1 |
0.04 % |
0 |
|
| Otter calf |
1 |
0.04 % |
0 |
|
| Other |
11 |
0.4 % |
4 |
0.4 % |
| Total no of malformations |
19 |
0.7 % |
30 |
3.2 % |
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However these in vitro production comprises first of in vitro maturation, second of
culture in special conditions with the use of co culture (Buffalo red liver cells, BRLC)
and addition of fetal calf serum. (FCS) and third culture to the blastocyst stage. It is
suggested that especially serum components seem to be responsible. Therefore, in addition
to the risk of extrapolation to the another species, extrapolation to just one of these
factors seems not warranted
In view of these findings, however, we firmly believe that there is a need for an
international registration of pregnancy course and outcome, and of the offspring form
culture of blastocysts.
References
1 Rijnders PM, Jansen CAM. The predictive value of day 3 embryo morphology for
blastocyst formation and implantation rate at day 5 in IVF. Hum. Reprod. 1996; 11S: 86
2 Rijnders PM, Jansen CAM. Selecting embryos and patients for transfer in IVF after
expression of the embryonic genome J.Ass. Reprod. Gen. 1997: 14:91S
3 Rijnders PM, Jansen CAM. The predictive value of day 3 embryo-morphology for
blastocyst formation and implantation rate at day 5 in IVF. Hum. Reprod. 1998; 10:(in
print)
4 Scholtes MCW, Zeilmaker GH. A prospective, randomized study of embryo transfer
results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril 1996,
65: 1245- 1248
5 Gudmundsson J, Lundqvist M, Rova, K, Simberg N, Lundkvist Ö. The outcome of IVF
treatment after two or five days of embryo culture. Hum. Reprod. 1998, 13S: 5- 6.
6 Kruip ThAM, den Daas JHG. In vitro-produced and cloned embryos: effects on pregnancy,
parturition and offspring. Theriogenology, 1997; 47: 43-53
7 van Wagtendonk- de Leeuw AM, Aerts BJG, den Daas JHG. Abnormal offspring following in
vitro- production of bovine preimplantation embryos: a field study. , Theriogenology, 1998
; 49: 883- 94
How is blastocyst culture performed ?
Still there are many unknown factors with regard to the optimum conditions to culture
embryos to the blastocyst stage. In the past cultures often were performed in the presence
of co-cultures. One theoretical disadvantage of these however is the risk of transmission
of micro-organisms.
Several new culture media are described. One study using the Medi-Cult M3 medium found a
miscarriage rate of 50 % after an established clinical pregnancy5. Some authors use serum,
others do not. It is clear that a lot of work is necessary to shed light on these various
aspects.
It is envisaged that an international registry will provide the tools to elucidate the
optimum culture conditions for blastocyst development.
How is the registry organized?
All centers that perform blastocyst cultures and transfer these embryos to the human are
invited to enter their data in the registry. This section however is password protected in
order to prevent unauthorized individuals to mess with these data. For every center that
wishes to enter data, one person responsible for the data can create a code and a password
to enter their data. They, and only they, can later add or modify their own data. Before
admission we will verify the identity of the individuals and the centers that wish to
participate. A center can opt to have their own data presented separately in conjunction
to the over-all data, or only as part of the over- all data. In the latter case other
centers will only see their data anonymously as part of the total registration
Data to be entered
The registry data are presented separately as well as in total. The following items are
presented:
Þ Name and Web-site of center
Þ Name and e-mail of responsible person
Þ Year of treatment
Þ Culture conditions:
Þ co-culture
Þ addition of serum, and
Þ type of culture medium
- between day 0 and day 3
- between day 3 and day 5-7
All data following (pregnancies, deliveries etc) are as a result of a treatment in the
year mentioned above. So if a treatment in December, the delivery will be in the year
afterwards. However it will be counted as belonging to the year of treatment.
The registry will comprise three levels : starter level, advanced
level and expert level. In the starter level you can only
enter the number of pregnancies and the number of babies born, the advanced level adds the
data as described below, whilst in the expert level you can enter the same data but then
specified as follows :
data from ICSI, fresh and frozen transfers
data from IVF, fresh and frozen transfers
data from other treatments, like SUZI, ibidem
Þ Total number of clinical pregnancies
Total
number of gestational sacs on ultrasound
Þ Total number of miscarriages
Þ Total number of ectopic pregnancies
Þ Total number of ongoing pregnancies
Þ Total number of ongoing pregnancies ending
before 24 weeks after FA
Þ Total number of deliveries after 24 weeks after FA
Þ Total number of children born
Þ Total number of singletons
and children
Þ Total number of twins and children
Þ Total number of triplets and children
Þ Total number of higher order pregnancies and children
Þ Total number of boys and girls
Þ Total number of minor congenital abnormalities
Þ Total number of major congenital abnormalities
Þ Description of individual major congenital abnormalities
Publications
No data shall be published without the explicit consent of all centers that wish to
participate in these publications. The names of the participating responsible individuals
will be mentioned. Authors can be referred to as "the international blastocyst
offspring study group"
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